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The impact of testosterone imbalance on depression and women's health

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Abstract

Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone (T) levels are related to depression and well-being in women, T plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6 ng/ml plasma free T a minimum of depression is detected. Lower levels are related to depression, osteoporosis, declining libido, dyspareunia and an increase in total body fat mass. Androgen levels in women decrease continuously to about 50% before menopause compared to a 20-year-old women. Androgen levels even decline 70% within 24 h when women undergo surgical removal of the ovaries. Conventional oral contraception or HRT cause a decline in androgens because of higher levels of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary syndrome. Social research suggests high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression. Higher androgen values are more pronounced at young ages and before and after delivery of a baby and might be responsible for the "baby blues". It was found that depression in pubertal girls correlated best with an increase in T levels in contrast to the common belief that "environmental factors" during the time of growing up might be responsible for emotional "up and downs". T replacement therapy might be useful in perimenopausal women suffering from hip obesity, also named gynoid obesity. Abdominal obesity in men and women is linked to type 2 diabetes and coronary heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal women might not only protect against obesity but also reduce the risk of developing these diseases. Antiandrogenic progestins might be useful for women suffering from hyperandrogenic state in peri- and postmenopause. Individual dosing schemes balancing side effects and beneficial effects are absolutely necessary. Substantial interindividual variability in T plasma values exists, making it difficult to utilize them for diagnostic purposes. Therefore a "four-level-hormone classification scheme" was developed identifying when estradiol (E) and T levels are out of balance. (1) Low E-low T levels are correlated with osteoporosis, depression, and obesity; (2) high E-low T with obesity, decreased libido; (3) high T-low E levels with aggression, depression, increased libido, and substance abuse; (4) high E-high T with type II diabetes risk, breast cancer and cardiovascular risk. Testosterone delivery systems are needed where beneficial and negative effects can be balanced. Any woman diagnosed for osteoporosis should be questioned for symptoms of depression.

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... Bu cinsiyet farkının altında yatan neden tam olarak bilinmese de dikkatler cinsiyet hormonlarının rolü üzerine yoğunlaşmıştır. 1,2 İnsanlarda testosteronun cinsellik, agresyon, uyku kontrolü, bilişsel işlevler, görsel uzaysal yetiler gibi depresyonla ilişkili belirtiler üzerinde etkilerinin olduğu gösterilmiştir. 3 Erkek depresyonlu hastalarda testosteron düzeyini araştıran çalışmalar çelişkili sonuçlar vermiştir. ...
... Yüksek doz anabolik androjen streoid kullanan sporcularda normal popülasyona göre daha çok depresif belirti gösterdikleri bildirilmiştir. 2 Bu sonuçlardan yola çıkarak risk etkenlerinin varlığında ortalamaya göre hem düşük, hem de yüksek testosteron düzeylerinin depresyonla ilişkili olduğu ileri sürülmüş; ortalama testosteron düzeyine sahip olmanın ise risk etkenleri olsa bile depresyon oranını azalttığı bildirilmiştir. Sonuç olarak testosteron düzeyi ile depresyon arasındaki ilişkinin parabolik bir eğri çizdiği ileri sürülmüştür. ...
... Sonuç olarak testosteron düzeyi ile depresyon arasındaki ilişkinin parabolik bir eğri çizdiği ileri sürülmüştür. 2 Depresyonlu kadın hastalarda testosteron düzeyini araştıran çalışma sayısı azdır. Kadınlarda testosteronun %60-70'i adrenal bez, %25-40'ı ise over kaynaklıdır. ...
Article
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Objective: Women suffer from depression more often than males, indicating that sex hormones might be involved in the etiology of this disease. The aim of this study was to investigate whether testosterone and 17-OH progesterone are related to the pathophysiology of depression in depressed women. We also investigated if any alteration takes place in these hormonal variables with antidepressant treatment. Methods: Forty female inpatients suffering from a depressive episode and 20 healthy female controls were recruited in the study. In the patient and control groups, serum total testosterone, 17-OH progesterone and SHBG levels were assayed. Pharmacotherapy was given to the patient group for 6-10 weeks (venlafaxine n=19, fluoxetine n=12, imipramine n=9). Hormonal measurements were repeated after the treatment in the patient group who responded to antidepressant treatment. Results: Serum testosterone levels were higher in the depressive women than in the healthy women. The testosterone levels were normalized by antidepressant treatment. 17-OH progesterone and SHBG levels did not differ between patients and controls. Conclusions: The result of normalized testosterone levels with pharmacotherapy suggests that testosterone may have a relationship with depression. Elevated levels of testosterone in depressed women might be a result of over activation of the adrenal glands, which are the main source of this hormone in women.
... Bu cinsiyet farkının altında yatan neden tam olarak bilinmese de dikkatler cinsiyet hormonlarının rolü üzerine yoğunlaşmıştır. 1,2 İnsanlarda testosteronun cinsellik, agresyon, uyku kontrolü, bilişsel işlevler, görsel uzaysal yetiler gibi depresyonla ilişkili belirtiler üzerinde etkilerinin olduğu gösterilmiştir. 3 Erkek depresyonlu hastalarda testosteron düzeyini araştıran çalışmalar çelişkili sonuçlar vermiştir. ...
... Yüksek doz anabolik androjen streoid kullanan sporcularda normal popülasyona göre daha çok depresif belirti gösterdikleri bildirilmiştir. 2 Bu sonuçlardan yola çıkarak risk etkenlerinin varlığında ortalamaya göre hem düşük, hem de yüksek testosteron düzeylerinin depresyonla ilişkili olduğu ileri sürülmüş; ortalama testosteron düzeyine sahip olmanın ise risk etkenleri olsa bile depresyon oranını azalttığı bildirilmiştir. Sonuç olarak testosteron düzeyi ile depresyon arasındaki ilişkinin parabolik bir eğri çizdiği ileri sürülmüştür. ...
... Sonuç olarak testosteron düzeyi ile depresyon arasındaki ilişkinin parabolik bir eğri çizdiği ileri sürülmüştür. 2 Depresyonlu kadın hastalarda testosteron düzeyini araştıran çalışma sayısı azdır. Kadınlarda testosteronun %60-70'i adrenal bez, %25-40'ı ise over kaynaklıdır. ...
Article
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ZET Amaç: Kadınların depresyona erkeklerden daha çok yakalanması, cinsiyet hormonlarının bu hastalığın etiyoloji-sinde bir etkisinin olabileceğini düşündürmektedir. Bu çalışmanın amacı depresyonlu kadınlarda testosteron ve 17-OH progesteronun depresyonun patofizyolojisiyle ilişkili olup olmadığını incelemektir. Ayrıca antidepresan tedaviyle bu hormonal parametrelerde herhangi bir değişim olup olmadığını da araştırdık. Yöntem: Depresif nöbet içinde bulunan 40 kadın hasta ve 20 sağlıklı kadın kontrol çalışmaya alındı. Hasta ve kontrol grubunda serum total testosteron, 17-OH progesteron ve SHBG düzeyleri ölçüldü. Hasta grubuna 6-10 hafta boyunca farmakoterapi uygulandı (venlafaksin s=19, fluoksetin s=12, imipramin s=9). Antidepresan tedaviye yanıt veren hasta grubunda hormonal ölçümler tedaviden sonra tekrarlandı. Bulgular: Serum testosteron düzeyi depresif kadınlarda sağlıklı kadınlarden yüksekti. Yüksek testosteron düzeyi antidepresan tedaviyle normale döndü. 17-OH progesteron ve SHBG düzeyleri hasta ve kontroller arasında farklı değildi. Sonuçlar: Farmakoterapiyle testosteronun normal düzeye inmesi, testosteronun depresyonla bir ilişkisinin olabileceğini düşündürmektedir. Depresif kadınlarda testosteronun yükselmiş düzeyi, kadınlarda bu hormonun ana kaynağı olan adrenal bezin aşırı aktivitesinin bir sonucu olabilir. (Anadolu Psikiyatri Derg 2010; 11:285-292) Anahtar sözcükler: Testosteron, progesteron, depresyon, kadın Testosterone and 17-OH progesteron levels in women with depression and the effects of antidepressant treatment ABSTRACT Objective: Women suffer from depression more often than males, indicating that sex hormones might be involved in the etiology of this disease. The aim of this study was to investigate whether testosterone and 17-OH pro-gesterone are related to the pathophysiology of depression in depressed women. We also investigated if any alteration takes place in these hormonal variables with antidepressant treatment. Methods: Forty female inpa-tients suffering from a depressive episode and 20 healthy female controls were recruited in the study. In the patient and control groups, serum total testosterone, 17-OH progesterone and SHBG levels were assayed. Pharmacotherapy was given to the patient group for 6-10 weeks (venlafaxine n=19, fluoxetine n=12, imipramine n=9). Hormonal measurements were repeated after the treatment in the patient group who responded to antidepressant treatment. Results: Serum testosterone levels were higher in the depressive women than in the healthy women. The testosterone levels were normalized by antidepressant treatment. 17-OH progesterone and SHBG levels did not differ between patients and controls. Conclusions: The result of normalized testosterone levels with pharmacotherapy suggests that testosterone may have a relationship with depression. Elevated levels of testosterone in depressed women might be a result of over activation of the adrenal glands, which are the main source of this hormone in women.
... In the general population research has established that clinical endocrine disorders, including both the hypo-and hyperfunction of endocrine glands, often result in psychiatric symptoms, with depression being the predominant clinical presentation [24]. Able-bodied females experience depression at higher rates than able-bodied males, suggesting that hormones may play a role in the etiology of the disease [25]. Furthermore, both low and high levels of testosterone in able-bodied women have been linked to depression [25]. ...
... Able-bodied females experience depression at higher rates than able-bodied males, suggesting that hormones may play a role in the etiology of the disease [25]. Furthermore, both low and high levels of testosterone in able-bodied women have been linked to depression [25]. In women without SCI, levels of total and free testosterone decline with age as women enter pre-menopause and may contribute to decreased mood [26]. ...
... Cramer's V = .616 is similar to previous research in both the able-bodied general [24] and able-bodied female [25] populations, such that abnormal testosterone levels (both low and high) were associated with depression. In this sample, Total T was not correlated with time from injury, which may provide evidence for a persistent change in total serum testosterone after SCI. ...
Article
Study design: Prospective case series. Objective: Investigate the association of testosterone and thyroid-stimulating hormone (TSH) levels with depressive symptoms in women after spinal cord injury (SCI). Setting: Community SCI clinic. Methods: Twenty-seven participants were enrolled in this study. Total testosterone (Total T) and TSH levels as well as the Center for Epidemiological Studies Depression Scale (CES-D) survey and monthly sexual activity were obtained from only 20 participants. Pearson's correlations were used to assess the relationship between age, time from injury, Total T level, TSH level, and CES-D total score. Follow-up analyses investigating the role of monthly sexual activity was also explored. Results: Participants' average age and time from injury was 44.4 ± 12.7 years old and 11.7 ± 8.89 years, respectively. Low Total T was observed in four participants and one of those participant's presented with low TSH as well. Nine women were classified as "at risk for clinical depression" on the CES-D (total score >15). Pearson's correlations revealed a significant association between time from injury and TSH (r = .536, p = .015), as well as CES-D total score (r = -.547, p = .013). Total T was associated with CES-D total score (ρ = -.541, p = .02). Conclusions: This study provides preliminary results on abnormal hormone levels and depressive symptoms in women after SCI. Twenty percent of this sample presented with low Total T, which was associated with increased depressive symptoms after accounting for time from injury. Further research is needed to investigate the impact of SCI on hormone function and mental health in women post SCI. Sponsorship: Sally Rynne National Association of Women's Health Quality Award 2002.
... 1,2 Both estrogen and testosterone (T) are mood elevators. 2,3 In addition to other actions, estrogen increases the rate of degradation of monoamine oxidase and intraneuronal serotonin transport, both of which serve to increase serotonin availability in the synapse, and therefore enhances mood. 4 Fluctuation in estrogen levels is encountered in various phases and interventions related to a woman's reproductive life, and periods of low estro-gen are associated with mood disturbances, including depression in many women. ...
... At about 0.4 to 0.6 ng/mL plasma-free T, a minimum level of depression is detected. 3 Rohr also compiled a 4-level classification scheme identifying when E and T levels are out of balance and can cause depression: (1) low E-low T correlated with osteoporosis, depression, and obesity; (2) high E-low T with obesity and decreased libido; ...
Article
Women are at higher risk throughout their reproductive lives than are men for major depression. Numerous molecular and clinical studies have implicated estrogen in modulating brain function including that related to mood. In an attempt to present a conceptual model, the literature of the past 30 years on mood and well-being throughout reproductive life is reviewed as it relates to activity of endogenous, bio-identical, and synthetic estrogen in women. Results indicate that sudden estrogen withdrawal, fluctuating estrogen, and sustained estrogen deficit are correlated with significant mood disturbance. Clinical recovery from depression postpartum, perimenopause, and postmenopause through restoration of stable/optimal levels of estrogen has been noted.
... Rohr 2002 mentioned that high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression 73 . In hypogonadal men whose often lethargic or depressive mood significantly improved under testosterone therapy 64 . . ...
... Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone levels are related to depression 73 . ...
... The role of oestrogen in women is not fully understood, but oestrogen fluctuations may be an important factor in the aetiology of affective disorder in women (100). Studies of testosterone-replacement therapy in hypogonadal men collectively suggest a benefit of testosterone on depressive symptoms, while knowledge on testosterone in women are more limited, with studies showing both improved and worsened mood (97,(101)(102)(103)(104). Oxytocin, on the other hand, has shown a positive effect on both positive, negative, and social cognitive symptoms of schizophrenia, and is shown to improve emotional recognition and social cognition in autism spectrum disorders (105)(106)(107). ...
Article
Background: Personalized medicine is a model in which a patient’s unique clinical, genetic, and environmental characteristics are the basis for treatment and prevention. Aim, method, and results: This review aims to describe the current tools, phenomenological features, clinical risk factors, and biomarkers used to provide personalized medicine. Furthermore, this study describes the target areas in which they can be applied including diagnostics, treatment selection and response, assessment of risk of side-effects, and prevention. Discussion and conclusion: Personalized medicine in psychiatry is challenged by the current taxonomy, where the diagnostic categories are broad and great biological heterogeneity exists within each category. There is, thus, a gap between the current advanced research prospects and clinical practice, and the current taxonomy is, thus, a poor basis for biological research. The discussion proposes possible solutions to narrow this gap and to move psychiatric research forward towards personalized medicine.
... However, the absent associations of baseline T and change in T with depressive symptom burden in the present study still add to the limited evidence about the potential antidepressant role of T in women. While some studies suggest that reduced, as well as increased T may negatively impact mental health in women and contribute to the onset of depressive symptom ( Rohr, 2002), most studies reported no significant associations ( Giltay et al., 2017;Kische et al., 2017;Morsink et al., 2007). Consequently, an according Cochrane review concludes that Table 2 Sex-specific associations of baseline total testosterone with depressive symptoms and depression. ...
Article
Background: The association between total testosterone (T) and depression mostly relies on single sex hormone assessment and remains inconclusive. Thus, we investigated the comparative predictive performance of baseline T and change in T with development of depressive symptoms and incident depressive episodes. Methods: We used data from 6493 primary care patients (2653 men and 3840 women) of the DETECT study (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment), including four-year follow-up, repeated immunoassay-based measurement of serum T and depressive symptoms assessed by the Depression Screening Questionnaire (DSQ). Cross-sectional and longitudinal associations of baseline T and one-year change in T with prevalent and incident depression were investigated using age- and multivariable-adjusted regression models. Results: Baseline T showed no association with prevalent or incident depressive symptoms and episodes in both sexes. In men, a positive change in T (higher T at one-year follow-up compared to baseline) was associated with a lower burden of depressive symptoms (β-coefficient per unit change in T: -0.17; 95% CI: -0.31 to -0.04) and lower risk of incident depressive symptoms (odds ratio per unit change in T: 0.84; 95% CI: 0.72-0.98) at four-year follow-up. In women, the association of T change with incident depressive episodes was rendered non-significant after multivariable adjustment. Discussion: The present study observed a sex-specific inverse association of T change, but not baseline T, with increased depressive symptom burden in men. Future studies should assess longitudinal changes in sex hormone status as predictor of adverse health outcomes related to low T.
... The present null findings among females are in line with most previous research reporting no association between androgens and depression in female adolescents [41,60]. Certainly, it was suggested that the increase in depression prevalence during adolescence in females is in part explained by sex hormones [81]. Accordingly, some authors reported higher testosterone concentrations as a predictor for depression in females [22] or lower salivary testosterone concentrations in female adolescent patients. ...
Article
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Although the link between androgens and depression is well established in adults, the effects of cofactors on this association are less clearly understood, particularly in youth. Epidemiological cohort study of adolescents in Dresden, Germany. Analyses comprised data of 985 individuals assessed at baseline and of 512 individuals at 1-year follow-up. We investigated multivariable regression models for cross-sectional and longitudinal associations of hair testosterone, dehydroepiandrosterone (DHEA), and their cortisol ratios with 12-month diagnoses of major depressive disorder (MDD) and MDD without any anxiety disorder assessed with standardized diagnostic interview (DIA-X-5), and with dimensional depression scores (PHQ-9, PROMIS), separately for males and females. The potential moderating effect of social support was determined. Cross-sectional analyses yielded inverse associations of testosterone and DHEA with MDD and MDD without any anxiety disorders in males. In cross-sectional and longitudinal analyses, baseline ratio cortisol/DHEA was significantly, inversely associated to PROMIS-depression in males. Only cross-sectional associations for ratio cortisol/DHEA and PROMIS-depression remained significant after Bonferroni-Holm correction. No robust associations were observed in female participants. Social support exerted no consistent moderating effect on the investigated association. The present observational cohort study showed no consistent association of hair androgen concentrations with depressive disorders in adolescents. However, findings provide some support for the association between the cortisol/DHEA ratio and depression in males. Longitudinal research designs in large samples are needed to understand the interplay between androgens, depression, and developmental and social factors in youth.
... On one side and in line with our findings, long-term testosterone-administration in older men in a recent randomized, double blind, placebo-controlled trial, did not improve cognitive function [31]. On the other hand, testosterone-treatment to non-dement individual was associated with better visuospatial functioning and deteriorations of verbal skills [32]. Additionally, in older women, higher testosterone concentrations predicted better categorical performance on cognitive tests [30]. ...
Article
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Objectives: Associations between androgens and depressive symptoms were mostly reported from cross-sectional and patient-based studies. Study design/main outcome measures: Longitudinal data from 4,110 participants of the Study of Health in Pomerania were used to assess sex-specific associations of baseline total and free testosterone, androstenedione and sex hormone-binding globulin with incident depressive symptoms and cognitive status at 5- and 10-year follow-up. Results: Despite sex-specific differences in depressive symptoms prevalence at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no associations between sex hormones and depressive symptoms. In age-adjusted longitudinal analyses, total testosterone was associated with incident depressive symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58-0.92). Similarly, age-adjusted analyses showed a positive association between sex hormone-binding globulin and cognitive status in men (β-coefficient per standard deviation: 0.44, 95% confidence interval: 0.13-0.74). In women, age-adjusted associations of androstenedione with baseline depressive symptoms (relative risk: 0.88, 95% confidence interval: 0.77-0.99) were found. None of the observed associations remained after multivariable adjustment. Conclusions: The present population-based, longitudinal study revealed inverse associations between sex hormones and depressive symptoms. However, the null finding after multivariable adjustment suggests, that the observed associations were not independent of relevant confounders including body mass index, smoking and physical inactivity. Furthermore, the low number of incident endpoints in our non-clinical population-based sample limited the statistical power and reduced the chance to detect a statistically significant effect.
... Since both male and female O. nerka die rapidly around the time of spawning, and 17β-estradiol levels are not altered in male O. nerka, the elevations in gonadotropins and loss of testosterone (and likely inhibin) signaling in both males and females appear to be the primary dyotic signals in salmon ( Table 2). The loss of 17β-estradiol (and inhibin) signaling also may be important for the demise of female O. nerka (Table 2; Jeffries et al. 2011), as supported by the high 17βestradiol concentrations in O. nerka prior to spawning (Table 2), and the lack of a decrease in testosterone signaling in post-menopausal women with aging (Rohr 2002). Although post-spawning female O. nerka circulating 17β-estradiol (and male O. nerka testosterone) is considerably higher than in mammals, their relative concentration declines by a far greater extent (Tables 2, 3, 4, and 5), thereby triggering robust dyotic signaling. ...
Article
Post-reproductive lifespan varies greatly among species; human post-reproductive lifespan comprises ~30–50% of their total longevity, while semelparous salmon and dasyurid marsupials post-reproductive lifespan comprises <4% of their total longevity. To examine if the magnitude of hypothalamic-pituitary-gonadal (HPG) axis dyscrasia at the time of reproductive senescence determines post-reproductive lifespan, we examined the difference between pre- and post-reproductive (1) circulating sex hormones and (2) the ratio of sex steroids to gonadotropins (e.g., 17β-estradiol/follicle-stimulating hormone (FSH)), an index of the dysregulation of the HPG axis and the level of dyotic (death) signaling post-reproduction. Animals with a shorter post-reproductive lifespan (<4% total longevity) had a more marked decline in circulating sex steroids and corresponding elevation in gonadotropins compared to animals with a longer post-reproductive lifespan (30–60% total longevity). In semelparous female salmon of short post-reproductive lifespan (1%), these divergent changes in circulating hormone concentration post-reproduction equated to a 711-fold decrease in the ratio of 17β-estradiol/FSH between the reproductive and post-reproductive periods. In contrast, the decrease in the ratio of 17β-estradiol/FSH in iteroparous female mammals with long post-reproductive lifespan was significantly less (1.7–34-fold) post-reproduction. Likewise, in male semelparous salmon, the decrease in the ratio of testosterone/FSH (82-fold) was considerably larger than for iteroparous species (1.3–11-fold). These results suggest that (1) organisms with greater reproductive endocrine dyscrasia more rapidly undergo senescence and die, and (2) the contribution post-reproduction by non-gonadal (and perhaps gonadal) tissues to circulating sex hormones dictates post-reproductive tissue health and longevity. In this way, reproduction and longevity are coupled, with the degree of non-gonadal tissue hormone production dictating the rate of somatic tissue demise post-reproduction and the differences in post-reproductive lifespans between species.
... Elevated testosterone was found in CMA and specifically in female OC users with MDD compared to controls. Consistent with this finding, higher rates of depression have been found in polycystic ovary syndrome (PCOS) characterized by high levels of androgens in females (383,384), elevated negative moodscale scores have been associated with upper normal free testosterone levels slightly in females (384), and increased testosterone has been correlated with depression in pubertal females (385). FSH was also reduced in MDD and remitted MDD patients compared to This study presents a significant step forward in understanding molecular sex differences in MDD and has important implications for future studies. ...
Thesis
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Schizophrenia and major depressive disorder (MDD) are disabling, poorly understood conditions with inadequate diagnostic and therapeutic technologies. They are characterized by clinical and epidemiological heterogeneity between male and female patients. Females have a higher prevalence of MDD, and in schizophrenia males have a higher incidence, earlier onset, more negative symptoms, and a worse prognosis and response to antipsychotic medication in schizophrenia. A better understanding of sex differences in these patients is needed to provide insight into biological mechanisms in these conditions and develop better diagnostic tools and therapies for males and females. This thesis sought to examine molecular sex differences in control subjects and in schizophrenia and MDD patients by profiling serum and prefrontal cortex (PFC) brain tissue. Multiplex immunoassay and microarray technologies were used to measure concentrations of proteins and small molecules in serum and gene expression in brain, respectively. Extensive differences in serum molecular concentrations were found between males and females experiencing a menstrual cycle, using oral contraceptives, and after menopause. These were involved in immune, metabolic, and endocrine processes and may play a role in driving sex differences in susceptibility and other characteristics of mental disorders. Furthermore, the hypothalamic-pituitary-gonadal (HPG) axis was altered in MDD and first onset, antipsychotic naive schizophrenia patients. Biological processes involving response to steroid hormone stimulus and estradiol were enriched among differentially expressed genes in the PFC in schizophrenia. However, investigation of sex-dependent differences in PFC gene expression in schizophrenia was limited by the small number of female samples available. Finally, higher serum concentrations of a number of immune and inflammatory molecules were associated with MDD and schizophrenia in males only and this may have consequences for immune hypotheses of these disorders. The research undertaken in this thesis has advanced the understanding of the mechanisms potentially involved in schizophrenia and MDD in males and females. Furthermore, sex and female hormonal status should routinely be taken into account during design and analysis of psychiatric molecular data to increase the reproducibility of such studies. This research shows that failing to consider these in biomarker studies can result in a high proportion of false positive findings and obscure important sex-dependent markers of mental disorders.
... It should also be noted that a number of studies have failed to support such a low T-depression link (reviewed in Ebinger et al., 2009). Among women the physiological pathways (if any) linking T to depression could differ, given the higher proportion of circulating T that derives from the adrenal androgens in females (Longcope, 1986) and the way T might interact physiologically with other reproductive steroids, such as estradiol (Rohr, 2002). That said, based on preliminary evidence, low T women might likewise be at increased risk for depression (Giltay et al., 2012;cf. ...
Article
Partnered adults tend to have lower risks of depression than do single individuals, while parents are more commonly depressed than non-parents. Low testosterone men, and possibly women, are also at greater risk of depression. A large body of research has shown that partnered parents have lower testosterone than single non-parents in some cultural settings, including the U.S. Here, we drew on a large (n = 2438), U.S.-population representative cohort of reproductive aged adults (age: 38.1 years ± 11.1 SD) to test hypotheses regarding the intersections between partnering and parenting, testosterone, socio-demographic characteristics, and depression outcomes. Men and women's depression prevalence did not vary based on testosterone. Partnered fathers had lower testosterone than single (never married, divorced) non-fathers, but were less commonly depressed than those single non-fathers. Partnered mothers had reduced testosterone compared to never married and partnered non-mothers. Never married mothers had higher depression prevalence and elevated depressive symptomology compared to partnered mothers; these differences were largely accounted for by key health-related covariates (e.g. cigarette smoking, BMI). We found significant three-way-interactions between socioeconomic status (SES), testosterone, and parenting for adults' depression risks. High testosterone, high SES fathers had the lowest prevalence of mild depression, whereas low testosterone, low SES non-fathers had the highest. Compared to other mothers, low SES, low testosterone mothers had elevated prevalence of mild depression. Overall, low SES, high testosterone non-mothers had substantially elevated depression risks compared to other women. We suggest that psychobiological profiles (e.g. a male with low testosterone) can emerge through variable psychosomatic and psychosocial pathways and the net effect of those profiles for depression are influenced by the social (e.g. partnering and parenting status; socioeconomic gradients), cultural (e.g. gender and family life domains), and ecological (e.g. the lived environment, particularly related to low SES and poverty) contexts in which individuals find themselves.
... Although some men may be motivated to exercise so as to increase their desirability, none of the physical fitness aspects in men were related to the number of sexual partners. This was contrary to common belief because exercise stimulates testosterone, [16] a libido-dependent hormone, that affects sex drive, sexual interest, and sexual function. [1] When men were isolated in the analysis, there were no relationships found between testosterone-producing activities (cardiovascular endurance, muscular endurance, and muscular strength) and sexual functioning. ...
Article
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Background: Obesity and inactivity have led to an increasing number of individuals with sexual dysfunctions (43% of women; 31% of men). Small bouts of exercise can drastically improve sexual functioning. Thus, the present study is designed to examine the effects of physical fitness and self-concept on sexual functioning. Materials and Methods: Fitness assessments and questionnaires were administered to 133 participants between the ages of 18 and 50 years. Physical fitness was assessed through body composition, cardiovascular endurance, muscular strength, and muscular endurance. Self-concept was presented as a total self-concept score and as six individual concepts of self. Sexual function was presented as both an aggregate score and five separate constructs of sexual functioning – fantasy/cognition, arousal, orgasm, behavior/experience, and drive/desire. Results: The results indicated that sexual behavior/experience was predicted by body fat percentage. In men, fantasy was related to total self-concept; sexual behavior/experience was related to likeability. In women, arousal was predicted by cardiovascular endurance. Total self-concept was related to both orgasm and sex drive/desire. Power and muscular strength were significantly related to number of sexual partners in women but not men. Conclusions: The present study adds to the growing body of evidence indicating a positive relationship between physical fitness and sexual health. Individuals with sexual dysfunctions, particularly women, who are not persuaded by the currently publicized benefits of physical activity, may be inclined to exercise to improve sexual functioning.
... It is known that the day and night rhythm requires circadian adaptation in almost all cells (for example, in human via cortisol) [12], but also circannual rhythms force hormonal adaptation in many animals and even human reproduction [13,14]: testosterone is high in summer in many animals and humans [15], facilitating sexuality in earlier centuries, when there was no influence of artificial light like today, so that babies were conceived in summer and born in spring, at a time when nature in the Northern Hemisphere provided enough fresh nutrients [16]. ...
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There are two forms of immune defense, the specific or adaptive immune defense and the unspecific innate immune defense. Vaccination is utilized against specific bacteria via the adaptive immune system. The innate immunity DNA stress defense is a non-toxic mechanism developed in yeasts and conserved in mammals and in plants. Although the steroidal hormone cascade has overtaken the stress response and allows superfast response via non-genomic receptors, the old innate immunity response is still mediated via the steroidal hormones cascade. The classical drug/receptor model has provided for many solutions, however, in antibiotics, cancer, and in severe mental diseases this model reaches to certain limits. The NIH/Department of Mental Health has developed a new model that shows severe mental diseases may be immune diseases that can be treated by replacing old diseased nerve cells by new healthy nerve cells, where the old innate immunity may be exploited. This means that severe mental diseases are physical diseases. A newly developed model, where modifications of the steroidal hormone cascade help to understand bipolarity, schizophrenia, and PTSD in men and women can be transferred to gynecological hormone modifications in women, where innate immunity is mediated via the same steroidal hormone cascade. Treatment via immune response via the DNA cascade should be developed in cancer, infections and severe mental disease, because foreign cells or diseased cells may be removed by the unspecific innate immunity.
... However, Eriksson et al. (16) and Backstrom and Aakvaag (10) discussed the contrary. It has been found that low testosterone in women can cause a number of physical and emotional symptoms, including depression, loss of sexual desire, and declining libido (24)(25)(26). Despite there being a limited number of studies concerning the effects of testosterone on mood, the results show that testosterone treatment per se, or with estrogen, improves mood in women (27). ...
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Background: Premenstrual syndrome (PMS) is reported by up to 85% of women of reproductive age. Although several studies have focused on the hormone and lipid profiles of females with PMS, the results are controversial. Objectives: This study was designed to investigate the association of hormonal and metabolic factors with PMS among Iranian women of reproductive age. Materials and methods: This study was a community based cross-sectional study. Anthropometric measurements, biochemical parameters, and metabolic disorders were compared between 354 women with PMS and 302 healthy controls selected from among 1126 women of reproductive age who participated in the Iranian PCOS prevalence study. P values < 0.05 were considered significant. Results: Prolactin (PRL) and triglycerides (TG) were significantly elevated in women with PMS, whereas their testosterone (TES), high density lipoprotein (HDL) and 17-hydroxyprogesterone (17-OHP) levels were significantly less than they were in women without the syndrome (P < 0.05). After adjusting for age and body mass index (BMI), linear regression analysis demonstrated that for every one unit increase in PMS score there was 12% rise in the probability of having metabolic syndrome (P = 0.033). Conclusions: There was a significant association between PMS scores and the prevalence of metabolic syndrome. Further studies are needed to confirm and validate the relationships between lipid profile abnormalities and metabolic disorders with PMS.
... Post-menopausal stage involves women without menstrual cycle for at least 12 months and incapable of becoming pregnant or having lactation (4). Mood disturbances including depression will lead to an epidemic proportion in 21st century worldwide (5). Depression is the main reason for disease related inability in women. ...
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Context: Menopause is characterized by amenorrhea and increase in the level of Follicular Stimulating Hormone (FSH) due to the permanent cessation of ovarian function. This process causes changes in hormonal and other serum markers. Depression is the leading cause of disease-related disabilities in women. Objectives: The aim of this review was to investigate the correlation between hormonal and petrochemical changes and depression with menopausal status. Data Sources: We searched in Cochrane Library, MEDLINE, PubMed, Google Scholar, Web of Science and Scopus, Embase, the reference lists of all related studies and major relevant review articles from 1960 to October 2014, and also abstracts from associated congresses and meetings, using terms related to hormonal and serum markers, depression and its symptoms. Study Selection: The survey included prospective, retrospective and case-control studies. The selected studies explored menopause in study population and investigated variables and different markers in depression or anxiety, as well as those measuring depression or anxiety intensity. Data Extraction: Items for which data were extracted included the date and place of publication, study design, sources, human species, age, control groups, selection and appraisal methods, outcome measurement tools, and author’s conclusions. One investigator (Mostafa Chashmposh) collected the relevant reports, whereas two other authors independently reviewed the published data and reported different hormonal markers related to depression as evaluated by different studies. Disagreements were resolved by the fourth reviewer’s decision. Results: The period of menopause is mostly associated with a gradual decline of estrogen activity and increased secretion of nocturnal melatonin. During menopausal transition, overnight cortisol levels were associated with changes in estrone glucuronide, testosterone, and FSH levels. In addition, whole blood serotonin concentration is reduced during menopause. Furthermore, lipid markers including total and LDL cholesterol levels increase during perimenopause. Moreover, plasma Brain Derived Neurotropic Factor (BDNF) concentration decreases significantly in postmenopausal period. Based on different studies, the reduction of hormones including estrogen, serotonin and BDNF during menopause are associated with depression in women. Further studies documented the relationship between depressed mood symptoms and cortisol levels. Conclusions: The available evidence suggests that transition to menopause and its changing hormonal and other serum markers are strongly associated with depressed mood among women.
... Animal research shows that testosterone has an immunosuppressive effect (e.g., Roberts and Peters, 2009;Roberts et al., 2007). Some studies have found that testosterone has also been successfully used in treating depression (Ebinger et al., 2009;Rohr, 2002). Therefore, individuals with lower testosterone levels may experience higher levels of both immune competence and depressive symptoms. ...
... This discrepancy may be a result of the higher doses of maternal testosterone (5 mg) used in the previous study compared with the present study (0.5 mg). The association between circulating testosterone and mood disorders has been suggested to be U-shaped, in which too-high or too-low levels cause behavioral dysfunction (30). Although the anxiety-like behavior observed in the female PNA offspring in the present study cannot be directly explained by high circulating androgens, the reduced AR expression in the amygdala suggests a compensatory response to the high prenatal testosterone exposure, a result implicating the amygdala as the CNS site underlying the changes in anxiety in the PNA offspring. ...
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During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone mi-croinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following tes-tosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. maternal androgen excess | anxiety | behavior | polycystic ovary syndrome | amygdala P olycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by excessive androgen secretion and abnormal insulin activity and affects up to 17% of women worldwide (1). Women with PCOS are at an increased risk of developing symptoms of anxiety and depression. In fact, over 60% of women with PCOS are diagnosed with at least one psychiatric disorder, such as depression, anxiety, or an eating disorder (2). Suicide attempts have also been shown to be seven times more common in women with PCOS than in healthy controls (3). The mechanisms underlying the development of PCOS are poorly understood. Although a genetic basis for PCOS has been suggested, the intrauterine milieu might also affect the reproductive/endocrine function of a child born to a PCOS mother in a manner that is independent of genetic inheritance or sex. It is also known that daughters of mothers with PCOS are at increased risk of developing the syndrome and that sons tend to suffer from obesity and insulin resistance (4). Thus, it has been proposed that PCOS originates during fetal development and that this might be, in part, a result of maternal androgen excess (5). Maternal testosterone levels in humans have been shown to affect brain morphology and function (6) and to be correlated to neural development and mental function (7). There is evidence for a crucial role of the hippocampus and the amygdala in the development of anxiety and depression, and that these neural circuits are affected by fluctuations in sex steroids in humans and in rodents (8). We have previously demonstrated that continuous exposure to dihydrotestosterone (DHT) from puberty until adulthood in female rats down-regulates androgen receptor (AR) expression in the hy-pothalamus and induces anxiety-like behavior in female rats (9). The increased rates of anxiety disorders and disruptive behavioral disorders among children with genetically induced hyperandrogenism further indicate that androgen excess may contribute to a higher risk of psychopathology (10). During pregnancy, androgens are metabolized to estrogens by the placenta in women and by the ovaries in rodents. Thus, the effects of testosterone on pregnancy are partly mediated by es-trogen (11). Women with PCOS exhibit high circulating androgen levels during pregnancy, which hypothetically could be related to the increased risk of mood disorders in their offspring (12). Significance Polycystic ovary syndrome (PCOS) is the leading cause of anovu-latory infertility characterized by excessive androgen secretion. PCOS women are at an increased risk of developing depression and anxiety disorders. Although the etiology of PCOS is unclear, it is proposed to originate during fetal development because of maternal androgen excess. We describe here, in rodent models reflecting the anxiety phenotype of PCOS, evidence for disordered androgen receptor function in the amygdala, together with changes in estrogen receptor-α, serotonergic and GABAergic genes in the amygdala, and hippocampus. These findings define a previously unknown mechanism that may be critical in understanding how maternal androgen excess has the potential to increase the risk of developing anxiety disorders in daughters and sons of PCOS mothers.
... 76 El E 2 y la FSH son las hormonas que de forma más consistente se han encontrado relacionadas con los síntomas depresivos, aunque algunos estudios también han sugerido que la falta de balance en la testosterona puede ocasionar síntomas depresivos y agresivos. 77 Del mismo modo, las progestinas pueden ocasionar diferentes efectos induciendo de forma ocasional ánimo disfórico o conducta alterada. 78 Solamente unos pocos estudios han evaluado el efecto de los niveles de dehidroepiandrosterona (DHEA) y el bienestar o la depresión en población clínica. ...
Article
Full-text available
Depression is an affective disorder that is more frequent in women than men. The etiology of depression disorders is multi-factorial, since social and biological influences have been determined. Coincidence between periods with hormonal fluctuations and affective alterations has lead to a hypothesis that considers fluctuations in gonadal hormones as a possible cause of depression in women. In this respect, pre-clinical studies by using laboratory animals (rodents) point toward a stronger relationship between hormonal oscillations and depressive behavior in different models designed to evaluate the antidepressant effect of drugs. This evidence could be interesting since in pre-clinical studies social factors are not included. Specifically, several authors have reported that depressive behavior is more prevalent in stages of rats' life characterized by low concentrations of gonadal hormones, such as postpartum, diestrous phase, lactancy and after ovariectomy. In contrast, a major presence of depressive behavior is observed in phases with higher concentration of hormones, like proestrus (a phase coincident with ovulation), pregnancy and after hormonal restitution with estrogens and progestins. Interestingly, the development of depressive behavior after ovariectomy has been established in female mice, with a critical period 12 weeks after ovaries extirpation. The participation of specific hormones in female depression could be studied in lab animals, since rodent female progress from a reproductive to a non-reproductive phase with vaginal and endocrine changes. Young females have a 4-5 days cycle named estrous cycle, in which each vaginal phase is associated with different concentrations of gonadal hormones. Although rodents do not exhibit menses, a state similar to peri- and post-menopause could be identified. Aging females exhibit irregular cycles before progressing to an estrous constant phase with elevated levels of estrogens. Decline of estrogen levels produces a persistent diestrous phase considered as a postmenopausal state. Aging rats in persistent diestrous, as well as ovariectomized females (the most economic model of post-menopause in lab animals) show physiological and behavioral changes associated to hormonal deprivation. Thus, they are considered a good model to evaluate affective and cognitive alterations as well as potential hormonal substitutive treatments. Clinical and epidemiologic studies report that perimenopause is linked to an increased risk of developing depression in women, or with the presence of more intense symptoms of depression. In agreement with Stages of Reproductive Aging Workshop (STRAW), perimenopause includes the period named transition to menopause plus one year after the last menses. This period is characterized by irregular menstrual cycles and fluctuations in levels of estrogens. In this stage, the levels of follicle-stimulating hormone (FSH) are elevated in order to further stimulate the production of estrogens from ovaries. Finally, concentrations of estrogens are significantly reduced in late perimenopause, although the levels of FSH continue to be increased. Fluctuations of estrogens and FSH have been related to symptoms such as affective alterations, hot flushes and insomnia, while hormonal deprivation in post-menopause is linked to changes in body fat, fatigue, cognitive disorders and reduction in bone density. Variations in estrogens and FSH level have been consistently related to depression symptoms in perimenopausal women, while changes in progestins and testosterone are associated with dysphoric mood and aggression, respectively. Thus, in agreement with the main hormonal hypothesis, a substitutive therapy with estrogens as an antidepressant therapy in peri- and post-menopausal women has been implemented. The results of different clinical studies are contradictory possibly due to methodological differences as the type of hormone used as an antidepressant therapy, dosage, time of administration of treatments and the period of hormonal deprivation in women. In a consistent manner, basic studies support the idea that steroidal gonadal hormones have antidepressant properties, but these seem to depend on both specific features of hormonal treatments and endocrine conditions in females. It has been reported that 17β-estradiol (E 2), ethinyl-estradiol (EE 2) and estradiol benzoate produce antidepressant-like actions in ovariectomized young females. Pharmacological studies have demonstrated that the serotonergic system has a major participation in the antidepressant-like effect of E 2, revealing its potential as a treatment for depressed women. In the same sense, estrogens that bind to estrogen receptors β (ERβ) are more effective to produce antidepressant- and anxiolytic-like effects than estrogens with higher affinity at ERα This evidence leads to consider ERβ as an important pharmacological target in depression. Studies evaluating estrogens in depression have determined that dosage is an important issue in the production of antidepressant-like effects. Dosage of estrogens that attain a physiological range have been reported to have more antidepressant efficacy in respect to lower or higher dose provoking infra- or supra-physiological levels of estradiol. In fact, a U-shape in the antidepressant effect of E 2 has been detected. Finally, timing of hormonal therapy seems to be a more relevant factor at moment to attain an antidepressant effect with estrogen treatment. Old rats (14 months) that received a prolonged estrogen treatment immediately after ovariectomy showed an antidepressant-like response which was not observed when treatment was began five months after ovaries extirpation. ERs are dependent on endogenous estrogens levels which suggest that a reduction in the target site of E 2 may be linked to its reduced antidepressant-like effect in females with a long-term hormonal deprivation. An apparently successful strategy to reduce depression in women has been to adjunct a hormonal treatment with antidepressant drugs in order to enhance antidepressant efficacy. Studies with a reduced number of patients have determined that combined therapy is able to reduce the scores in the Hamilton Depression Scale, and to allow the effect of antidepressant drugs in women with refractory depression. At this respect, basic studies have established that estrogens facilitate the antidepressant effects of several antidepressant drugs. It was reported that the anxiolytic effect of desipramine was more evident in the proestrus, a phase characterized by high levels of estrogens and progesterone in young females. Both estrogens and progesterone participate in the anxiolytic effect of desipramine, although the synergism with estradiol was more significant. By using specific animal models of antidepressant effects, it was found that E 2 facilitated the antidepressant effect of fluoxetine, desipramine, venlafaxine and bupropion in young, ovariectomized female rodents. In contrast, a chronic study using old, ovariectomized female rats showed that estradiol valerate was unable to improve the antidepressant effect of citalopram, even though the antidepressant efficacy of both estrogen and citalopram was established previously. Differences in results could be due to variations in methodological aspects such as age of rats (young, three months, versus old, 15 month), type of estrogen used in each study (E 2 versus estradiol valerate), animal model of depression (forced swimming test, acute model, versus chronic mild stress model), type of antidepressant used (citalopram in the last case), and dosage for both estrogens and antidepressant drugs. Interestingly, the strategy of a combined treatment could be a therapeutic advantage for those women that suffer depression associated to endocrine changes. Evidence from clinical and basic studies should be taken into account at moment to select the most advantageous therapy to treat depression in mature women.
... Nevertheless, the patient reported experiencing particularly aggressive behaviour during the third trimester of pregnancy, which can be explained by a hyperandrogenic state from that gestational time onward. 12 The male neonate had normal sexual phenotypical characteristics. ...
Article
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We report a rare case of hyperreactio luteinalis presenting as an incidental finding during caesarean section in an uncomplicated spontaneous singleton pregnancy. Caesarean section was performed due to failure to progress in labour, and delivered a healthy male neonate. The mother's analytical tests revealed a hyperandrogenic state without any other relevant alterations. Ovarian volume and testosterone serum concentration normalised in 2&emsp14;months. The expectant management of this case permitted conservation of both ovaries in a young woman without adding morbidity.
... 76 El E 2 y la FSH son las hormonas que de forma más consistente se han encontrado relacionadas con los síntomas depresivos, aunque algunos estudios también han sugerido que la falta de balance en la testosterona puede ocasionar síntomas depresivos y agresivos. 77 Del mismo modo, las progestinas pueden ocasionar diferentes efectos induciendo de forma ocasional ánimo disfórico o conducta alterada. 78 Solamente unos pocos estudios han evaluado el efecto de los niveles de dehidroepiandrosterona (DHEA) y el bienestar o la depresión en población clínica. ...
Article
Full-text available
Depression is an affective disorder that is more frequent in women than men. The etiology of depression disorders is multi-factorial, since social and biological influences have been determined. Coincidence between periods with hormonal fluctuations and affective alterations has lead to a hypothesis that considers fluctuations in gonadal hormones as a possible cause of depression in women. In this respect, pre-clinical studies by using laboratory animals (rodents) point toward a stronger relationship between hormonal oscillations and depressive behavior in different models designed to evaluate the antidepressant effect of drugs. This evidence could be interesting since in pre-clinical studies social factors are not included. Specifically, several authors have reported that depressive behavior is more prevalent in stages of rats' life characterized by low concentrations of gonadal hormones, such as postpartum, diestrous phase, lactancy and after ovariectomy. In contrast, a major presence of depressive behavior is observed in phases with higher concentration of hormones, like proestrus (a phase coincident with ovulation), pregnancy and after hormonal restitution with estrogens and progestins. Interestingly, the development of depressive behavior after ovari-ectomy has been established in female mice, with a critical period 12 weeks after ovaries extirpation. The participation of specific hormones in female depression could be studied in lab animals, since rodent female progress from a reproductive to a non-reproductive phase with vaginal and endocrine changes. Young females have a 4-5 days cycle named estrous cycle, in which each vaginal phase is associated with different concentrations of gonadal hormones. Although rodents do not exhibit menses, a state similar to peri- and post-menopause could be identified. Aging females exhibit irregular cycles before progressing to an estrous constant phase with elevated levels of estrogens. Decline of estrogen levels produces a persistent diestrous phase considered as a post-menopausal state. Aging rats in persistent diestrous, as well as ovari-ectomized females (the most economic model of post-menopause in lab animals) show physiological and behavioral changes associated to hormonal deprivation. Thus, they are considered a good model to evaluate affective and cognitive alterations as well as potential hormonal substitutive treatments. Clinical and epidemiologic studies report that perimenopause is linked to an increased risk of developing depression in women, or with the presence of more intense symptoms of depression. In agreement with Stages of Reproductive Aging Workshop (STRAW), perimenopause includes the period named transition to menopause plus one year after the last menses. This period is characterized by irregular menstrual cycles and fluctuations in levels of estrogens. In this stage, the levels of follicle-stimulating hormone (FSH) are elevated in order to further stimulate the production of estrogens from ovaries. Finally, concentrations of estrogens are significantly reduced in late perimenopause, although the levels of FSH continue to be increased. Fluctuations of estrogens and FSH have been related to symptoms such as affective alterations, hot flushes and insomnia, while hormonal deprivation in post-menopause is linked to changes in body fat, fatigue, cognitive disorders and reduction in bone density. Variations in estrogens and FSH level have been consistently related to depression symptoms in perimenopausal women, while changes in progestins and testosterone are associated with dysphoric mood and aggression, respectively. Thus, in agreement with the main hormonal hypothesis, a substitutive therapy with estrogens as an antidepressant therapy in peri- and post-menopausal women has been implemented. The results of different clinical studies are contradictory possibly due to methodological differences as the type of hormone used as an antidepressant therapy, dosage, time of administration of treatments and the period of hormonal deprivation in women. In a consistent manner, basic studies support the idea that steroi-dal gonadal hormones have antidepressant properties, but these seem to depend on both specific features of hormonal treatments and endocrine conditions in females. It has been reported that 17β-estradiol (E2), ethinyl-estradiol (EE2) and estradiol benzoate produce antidepres-sant-like actions in ovariectomized young females. Pharmacological studies have demonstrated that the serotonergic system has a major participation in the antidepressant-like effect of E2, revealing its potential as a treatment for depressed women. In the same sense, estrogens that bind to estrogen receptors β (ERβ) are more effective to produce antidepressant- and anxiolytic-like effects than estrogens with higher affinity at ERa This evidence leads to consider ERβ as an important pharmacological target in depression. Studies evaluating estrogens in depression have determined that dosage is an important issue in the production of antidepressant-like effects. Dosage of estrogens that attain a physiological range have been reported to have more antidepressant efficacy in respect to lower or higher dose provoking infra- or supra-physiological levels of estradiol. In fact, a U-shape in the antidepressant effect of E2 has been detected. Finally, timing of hormonal therapy seems to be a more relevant factor at moment to attain an antidepressant effect with estrogen treatment. Old rats (14 months) that received a prolonged estrogen treatment immediately after ovariectomy showed an antidepressant-like response which was not observed when treatment was began five months after ovaries extirpation. ERs are dependent on endogenous estrogens levels which suggest that a reduction in the target site of E2 may be linked to its reduced antidepressant-like effect in females with a long-term hormonal deprivation. An apparently successful strategy to reduce depression in women has been to adjunct a hormonal treatment with antidepressant drugs in order to enhance antidepressant efficacy. Studies with a reduced number of patients have determined that combined therapy is able to reduce the scores in the Hamilton Depression Scale, and to allow the effect of antidepressant drugs in women with refractory depression. At this respect, basic studies have established that estrogens facilitate the antidepressant effects of several antidepressant drugs. It was reported that the anxiolytic effect of desipramine was more evident in the proestrus, a phase characterized by high levels of estrogens and progesterone in young females. Both estrogens and progesterone participate in the anxiolytic effect of desipramine, although the synergism with estradiol was more significant. By using specific animal models of antidepressant effects, it was found that E2 facilitated the antidepressant effect of fluoxetine, desipramine, venlafaxine and bupropion in young, ovariectomized female rodents. In contrast, a chronic study using old, ovariectomized female rats showed that estradiol valerate was unable to improve the antidepressant effect of citalopram, even though the antidepressant efficacy of both estrogen and citalopram was established previously. Differences in results could be due to variations in methodological aspects such as age of rats (young, three months, versus old, 15 month), type of estrogen used in each study (E2 versus estradiol valerate), animal model of depression (forced swimming test, acute model, versus chronic mild stress model), type of antidepressant used (citalopram in the last case), and dosage for both estrogens and antidepressant drugs. Interestingly, the strategy of a combined treatment could be a therapeutic advantage for those women that suffer depression associated to endocrine changes. Evidence from clinical and basic studies should be taken into account at moment to select the most advantageous therapy to treat depression in mature women.
... Women during the senescence years are mostly affected due to estrogen deficiency due to menopause or bilateral ovariectomy. This condition leads to accelerated bone loss and promotes the development of postmenopausal osteoporosis [7,8]. ...
Background: Post-menopausal osteoporosis has long been treated and prevented by estrogen replacement therapy (ERT). Despite its effectiveness, ERT is associated with serious adverse effects. Labisia pumila var. alata (LP) is a herb with potential as an alternative agent to ERT due to its phytoestrogenic, antioxidative and anti-inflammatory effects on bone. This study aimed to determine the effects of LP supplementation on bone biomechanical strength of postmenopausal osteoporosis rat model. Methods: Ninety-six female Sprague-Dawley rats aged 4 to 5 months old were randomly divided into six groups; six rats in the baseline group (BL) and eighteen rats in each group of; Sham- operated (Sham), ovariectomised control (OVXC) and ovariectomised with daily oral gavages of Premarin at 64.5 μg/kg (ERT), LP at 20 mg/kg (LP20) and LP at 100 mg/kg (LP100) respectively. These groups were subdivided into three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out for biomechanical strength analysis using Instron Universal Model 5848 Micro Tester. Results: OVXC group showed deterioration in the bone biomechanical strength with time. Both ERT and LP supplemented rats showed improvements in bone strength parameters such as maximum load, displacement, stiffness, stress, and Young Modulus. The most improved bone strength was seen in rats given LP at the dose of 100 mg/kg for nine weeks. Conclusion: LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomy-induced bone biomechanical changes.
... Paradoxically, low-dose T supplementation in women seems to improve mood and reduce anxiety in women with treatment-resistant-depression, when used as a complementary therapy (Miller et al., 2009). Testosterone effects on mood also seem to be dose-dependent, with high T levels associated to depression (Rohr, 2002). ...
Article
Full-text available
Background: The role of testosterone (T) in the pathophysiology of affective disorders and anxiety is broadly supported. Evidence suggests that T has anxiolytic and antidepressant properties. One proposed route for the central effects of T is its interaction with the gamma-aminobutyric acid (GABA) system. We explored the relationship between T levels and GABA+ levels in anterior-cingulate (ACC) and the posterior-cingulate (PCC) regions in depressed women, using magnetic resonance spectroscopy (1H-MRS). Methods: Twenty-one depressed patients with regularly cycling who were not taking hormonal or psychotropic drugs were recruited. We assessed severity of depression using the Hamilton Depression Rating Scale (HDRS). Blood samples were taken for quantification of free (FT) and total testosterone (TT) on the day of the magnetic resonance (MR) scan. We evaluated GABA+ levels in the PCC and ACC, using the Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence. Pearson correlations were used to evaluate the association between FT, TT, GABA+ concentrations, and HDRS scores. Results: TT and FT levels were positively correlated with GABA+ levels in the PCC. No correlation was observed between T levels and GABA+ levels in the ACC. The HDRS total scores correlated negatively with FT levels. Limitations: Limitations include the cross-sectional evaluation and the lack of a comparative healthy group. Conclusions: Our findings suggest that the potential anxiolytic and antidepressant properties of T are related to increased GABA+ levels in the PCC. This observation may contribute to increased understanding of the role of T in depressive and anxiety symptoms in women.
... Egzersiz, libidoya bağlı bir hormon olan testosteronu uyarır (Rohr, 2002) ve genital bölgeye olan kan akıĢını tetikleyen sempatik sinir sistemini hareket geçirir (Meston, 2000). (Penhollow & Young, 2008). ...
... These negative effects for patients with PCOS may not be compensated for by the possibly beneficial effects of increased androgen levels. Another explanation could be that some studies showed significant positive correlations between psychoemotional disorders such as depression and increased serum androgens, although a causal relationship is unclear [42][43][44]. There are therefore still unanswered questions regarding the From other factors evaluated in our study, a clear association was found for obesity with obviously decreased sexual function. ...
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Full-text available
To investigate sexual function in Chinese women with polycystic ovary syndrome (PCOS) and to explore the correlation with clinical and biochemical characteristics. A cross-sectional study was designed in 1000 PCOS women, aged 18–45 years, via the Chinese version of Female Sexual Function Index (FSFI) evaluating sexual function, with additional questions possibly related to sexual life. Clinical and biochemical characteristics likely to affect sexual function were determined, including anthropometric indicators, serum levels of hormones, luteinizing hormone to follicle-stimulating hormone ratio (LH/FSH ratio), prolactin (PRL), total testosterone (TT), free androgen index (FAI), sex-hormone-binding globulin (SHBG), glucose, and lipid metabolism indicators. Nine hundred ten PCOS women participated in the study, 685 patients were included after screening, and 211 were suitable to detect correlations of clinical and biochemical characteristics with sex function parameters. The mean total FSFI score was 24.19 ± 2.8; 79.56% of the women were at risk of female sexual dysfunction (FSD). Women doing regular aerobic exercise and use of contraception had higher FSFI scores, while those with a desire to conceive and clinical signs of hyperandrogenism had lower FSFI scores. There were negative associations of FSFI scores with age and body fat distribution. No significant associations between FSFI scores and hormonal factors (surprisingly including SHBG) were found, except for total testosterone and satisfaction (OR = 0.976, p = 0.002). HOMA-IR was significantly related to reduced desire score (OR = 0.914, p = 0.004) and lubrication score (OR = 0.964, p = 0.044). PCOS was associated with a high risk of FSD (defined according to FSFI) in about 80% of the women in our study, and clinical characteristics play a more important role.
... It is also possible that the relationship between testosterone levels and depression in women may be parabolic. For example, the deviation of testosterone levels from an optimum range would result in adverse effects, and there are even some studies that support this theory [50,51]. ...
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Full-text available
Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.
... The main symptoms of MDD include severe sadness, anxiety, cognitive deterioration, and suicidal thoughts [4]. Although its etiology is uncertain, genetic predisposition, developmental deficits, hormonal imbalance, and a stressful lifestyle may increase the risk for MDD [5][6][7][8][9][10]. ...
Article
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Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 406 patients with depression have now undergone this neuromodulation therapy, and 30 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS among patients with treatment-resistant depression was estimated to be approximately 54% across clinical studies. Although some studies showed its stimulation e�cacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms.
... Previous studies have demonstrated that the incidence of PSD in women is higher than that of men. [27] In this study, the expression of E2 and FSH were significantly higher and lower, respectively, in female patients the experimental group when compared with the control group. Conversely, the expression of T in the experimental group was significantly higher than in the control group in male patients. ...
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Objective: To investigate the effect of edaravone on depression relief in symptomatic patients with intracranial stenosis and its relationship with the expression of sex hormones. Methods: We recruited 112 patients with symptomatic intracranial arterial stenosis from Renmin Hospital, Wuhan University, between October 2014 and October 2017. All patients were divided into the traditional or experimental (traditional treatment + intravenous infusion of edaravone 30 mg twice a day for 14 days) treatment groups. The general clinical data were collected, and neurological functional recovery using the Modified Rankin Scale (mRS) and National Institute of Health stroke scale (NIHSS) scores were recorded. Symptom Checklist 90 (SCL-90) was used to assess the general psychological changes of the patient, followed by the 24 Hamilton Depression Scale (HAMD) to examine the incidence of post-stroke depression (PSD). This divided the patients into the mild, moderate, and severe depression groups. Next, we measured the serum protein expression of the sex hormones estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), prolactin (PRL), and luteinizing hormone (LH). Results: The mRS and NIHSS scores were significantly lower in the experimental group than in the control group (P < .05). There was no significant difference in SCL90 score before intervention (P > .05); the scores were significantly lower in the experimental group after intervention (P < .05). There was a significant difference in SCL-90 and HAMD scores between groups before treatment (P < .05), with significantly lower scores in the experimental group post-treatment (P < .05). The incidence of depression was significantly reduced in the experimental group post-treatment. Furthermore, the expression of E2 and FSH was significantly higher (P < .01) and lower (P < .001), respectively, in women than in men in the experimental group post-treatment. Interestingly, the expression of T was significantly lower in men in the experimental group post-treatment (P < .001). Conclusion: Edaravone significantly improved the clinical efficacy of stent implantation in intracranial artery stenosis treatment by alleviating depression and reducing the incidence of PSD.
... Interaction between the HPA axis and the hypothalamic-pituitary-gonadal axis was also observed with increased HPA and in parallel diminished hypothalamicpituitary-gonadal activity in depressed males and females [6,24] as well as in AD patients [22]. In women suffering from depression, lower plasma estrogen levels and increased plasma androgen levels have been observed [25], whereas testosterone levels were found decreased in depressed men [26,27], although some studies reported no such correlation [28][29][30]. ...
Article
Background: Depression is a common comorbid condition with atopic dermatitis (AD), particularly during the active disease cycle. Controversial results regarding the contribution of biological sex, immunoglobulin E (IgE) sensitization, and cortisol on AD severity and comorbid depression justify further investigation. Objective and methods: To explore the influence of sex and IgE sensitization on biochemical and psychological parameters, and severity of AD, a case-control study of 105 volunteers (56 AD, 49 healthy controls (HC); 50 males, 55 females) was conducted over 10 weeks, starting at dermatological symptom onset. Disease severity, serum IgE, cortisol and testosterone levels, and depression scores were assessed at study baseline and after 10 weeks of conventional treatment. Results: Dermatological severity differed among AD males by IgE sensitization and was elevated in males with extrinsic atopic dermatitis (EAD). Hamilton Depression Rating Scale (HAMD) scores were elevated in all patients at study baseline and improved with symptom reduction to HC levels, except female EAD. Severity of depression and dermatitis were correlated in EAD males at baseline and at week 10. Serum cortisol was elevated in male EAD at baseline, in contrast to males with intrinsic atopic dermatitis (IAD) at week 10. In addition, cortisol levels were found negatively correlated with SCORAD and HAMD scores in EAD males at week 10. Conclusion: Pathophysiological features of AD and depression are likely related to different inflammation-based effects and appear to be biological sex-dependent. Cortisol levels depend on biological sex and IgE sensitization in AD and increase in males with EAD at exacerbation and IAD males at resolution. Biological sex-related disease triggers, IgE sensitization, and cortisol levels are important for the understanding of the mechanisms underlying AD and comorbid depression.
... Kische et al. (2017) reported no association between androgen levels and depression in the general population. However, two other studies proposed an association between androgen levels and depression (Rohr, 2002;Soares and Zitek, 2008). Hyperandrogenism is the key presentation of PCOS. ...
Article
Study question: Is polycystic ovarian syndrome (PCOS) in women associated with the increasing incidence of depression in an East Asian population? Summary answer: Younger PCOS patients (aged 15-29 years), but not middle-aged patients, have an increased risk of depression in Taiwan. What is known already: During reproductive age, 6-10% of women have PCOS. Among them, ~40% experience depression, mostly at young ages. Study design, size, duration: This is a retrospective population-based cohort study analysing depression risk in Taiwanese women using data from a nationwide database containing 1998-2013 data of nearly 1 million people. Participants/materials, setting, methods: We included 15- to 50-year-old women newly diagnosed with PCOS during 1998-2013 from the Taiwan National Health Insurance Research Database as the PCOS cohort (n = 7684) and then randomly matched them 4 : 1 by sex, age and index year with women without PCOS as the comparison cohort (n = 30 736). We used multivariable Cox proportional hazard regression analysis to determine the association between PCOS and depression risk [hazard ratio (HR) with 95% confidence interval (CI)]. Main results and the role of chance: The incidence of depression was higher in the PCOS group than in the comparison group (6.67 vs. 4.82 per 1000 person-years; adjusted HR = 1.28, 95% CI = 1.12-1.46). PCOS patients aged 15-29 years had a significantly higher depression risk (adjusted HR = 1.39, 95% CI = 1.18-1.65); no such significant association was noted among patients aged 30-39 years and 40-50 years. Limitations, reasons for caution: A history of malignancy, which may increase depression, could not be obtained for our study patients. Moreover, we could not obtain a family history of depression, a relevant risk factor for depression. Finally, the database has no records of body mass index, which may influence depression outcome. Wider implications of the findings: In Taiwan, younger PCOS patients (15-29 years), but not the middle-aged patients, have an increased risk of depression. Our findings provide vital information to patients, clinicians, the Taiwan Government and other developing Asian countries to improve the PCOS treatment strategies in the future. Routine screening for depression in PCOS patients may be implemented into the health practice. Study funding/competing interest(s): This study was supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133 004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-), Tseng-Lien Lin Foundation, Taichung, Taiwan and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. No competing interest existed. Trial registration number: N/A.
... The fact that this association was observed in premenopausal women only might be related to physiological changes of testosterone levels over a woman's lifespan. Between 20 and 40 years, a steep decline of testosterone levels can be seen in women (40). Premenopausal women could be therefore more sensitive to the (pathophysiological) increase of testosterone level. ...
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Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group.
... The sexual dimorphism observed in the prevalence of depression, with women having greater risk, suggests a role of sex hormones in the development of depression. Both low and high testosterone levels are associated with depression in women [79]. There are no data evaluating the effects of testosterone replacement on depression in adolescent males. ...
Article
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The prevalence of obesity continues to rise in adult and pediatric populations throughout the world. Obesity has a direct impact on all organ systems, including the reproductive system. This review summarizes current knowledge about the effects of obesity on the male reproductive system across age, highlighting the need for more data in children and adolescents. Male hypogonadism is commonly seen in patients with obesity and affects the onset, duration, and progression of puberty. Different pathophysiologic mechanisms include increased peripheral conversion of testosterone to estrone and increased inflammation due to increased fat, both of which lead to suppression of the hypothalamic-pituitary-gonadotropin (HPG) axis and delayed development of secondary sexual characteristics in adolescent males. Evaluation of the HPG axis in obesity includes a thorough history to exclude other causes of hypogonadism and syndromic associations. Evaluation should also include investigating the complications of low testosterone, including increased visceral fat, decreased bone density, cardiovascular disease risk, and impaired mood and cognition, among others. The mainstay of treatment is weight reduction, but medications such as testosterone and clomiphene citrate used in adults, remain scarcely used in adolescents. Male hypogonadism associated with obesity is common and providers who care for adolescents and young adults with obesity should be aware of its impact and management.
... In the case of serotonin, numerous studies have shown it to be related to criminality, although in complex and still only partially understood ways (Hillbrand & Pallone, 1994;Rowe, 2002;Virkkunen & Linnoila, 1993). Rather than operating through intermediary personality traits such as risk-taking and enhanced pain tolerance (as in the case of dopamine), low serotonin activity seems to increase offending probabilities primarily by impacting symptoms of mental illness such as depression (Josephs et al., 2012;Rohr, 2002) and schizophrenia (Birger et al., 2003;Lagoa, Santos, Pinheiro, & Magalhães, 2009). ...
... Farag et al peroxidation affecting the inflammatory process and acne pathogenesis. 31 AV is a multifactorial skin disease, in which hormones including glucocorticoids were implicated. 32 Confirming this speculation, our AV patients demonstrated a significant increase in their cortisol serum levels than their matched peers. ...
... Interestingly, clinical studies have failed to show effectiveness for testosterone administration as an augmentation strategy in the management of depression in men [158], whereas administration of low-dose testosterone in women with treatment-resistant MDD has been observed to significantly improve depressive symptoms in comparison to placebo [159]. ese paradoxical findings are consistent with the higher sensitivity of females to androgens, as higher androgen exposure has been noted to exert a definite negative influence in mood in females [160,161]. Future studies should address these differences between gender and their clinical relevance. ...
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Depression is currently recognized as a crucial problem in everyday clinical practice, in light of ever-increasing rates of prevalence, as well as disability, morbidity, and mortality related to this disorder. Currently available antidepressant drugs are notoriously problematic, with suboptimal remission rates and troubling side-effect profiles. Their mechanisms of action focus on the monoamine hypothesis for depression, which centers on the disruption of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain. Nevertheless, views on the pathophysiology of depression have evolved notably, and the comprehension of depression as a complex neuroendocrine disorder with important systemic implications has sparked interest in a myriad of novel neuropsychopharmacological approaches. Innovative pharmacological targets beyond monoamines include glutamatergic and GABAergic neurotransmission, brain-derived neurotrophic factor, various endocrine axes, as well as several neurosteroids, neuropeptides, opioids, endocannabinoids and endovanilloids. This review summarizes current knowledge on these pharmacological targets and their potential utility in the clinical management of depression.
... 4,13,14 Indeed, low testosterone levels have been associated with MDD in men, [15][16][17][18] although associations in women are inconsistent. 8,17,19,20 Given these associations, we hypothesized that MDD or the use of antidepressants increases the vulnerability for testosterone level alterations. Therefore, we aimed to determine the associations between testosterone and MetS in older adults and test whether this association is stronger in depressed or antidepressant-using patients. ...
Article
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Objectives Older age and Major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and Metabolic Syndrome (MetS) in men, though associations in women are less clear. Therefore, we investigated whether testosterone is associated with MetS and whether this association is different for depressed and non‐depressed older men and women. Methods In this prospective cohort study, 478 participants (349 patients with MDD and 129 controls) aged between 60 and 93 years from the Netherlands Study of Depression in Older Persons (NESDO) were included. Total testosterone (TT) and sex‐hormone binding globulin (SHBG) levels were measured using a second generation radioimmune assay. Free testosterone (FT) was calculated based on TT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Results A higher risk for MetS was found in men with low FT and TT (Odds Ratio [OR]: 0.67, 95% confidence interval [95%CI]: 0.47‐0.95 and OR: 0.51, 95%CI: 0.34‐0.75), and in women with high FT (OR: 1.41, 95%CI: 1.08‐1.82). Strong associations in the same direction were found with adiposity, glucose and plasma lipid MetS components at baseline, but not with changes in these components at two‐year follow‐up. The associations did not significantly differ between MDD patients and controls. Conclusions Independently of having MDD, low testosterone levels in men, and in contrast, high testosterone levels in women were significantly associated with MetS and its components.
... This discrepancy may be a result of the higher doses of maternal testosterone (5 mg) used in the previous study compared with the present study (0.5 mg). The association between circulating testosterone and mood disorders has been suggested to be U-shaped, in which too-high or too-low levels cause behavioral dysfunction (30). Although the anxiety-like behavior observed in the female PNA offspring in the present study cannot be directly explained by high circulating androgens, the reduced AR expression in the amygdala suggests a compensatory response to the high prenatal testosterone exposure, a result implicating the amygdala as the CNS site underlying the changes in anxiety in the PNA offspring. ...
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During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.
... Social research suggests high androgen levels cause aggressive behavior in men and women, a consequence of which could be depression. 31 The present study showed significant relationships between QoL and some androgens including FAI and DHEAS levels, associations that remained significant even after adjustment for hirsutism, whereas QoL had no relationship with total testosterone, gonadotropins levels. ...
Article
Objectives: We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. Methods: Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. Results: The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = -0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = -0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. Conclusion: Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.
Article
Objective: To explore the relationship between the serum level of C-reactive protein and the post-stroke depression (PSD). Methods: One hundred and forty four patients with acute stroke were screened for the diagnosis of PSD according to DSM-IV. All patients assessed with ZUNG Self-Rating Depression Scale as Preliminary screening, and PSD group were sub-divided into three groups as mild, middle, and severe PSD groups according to the 24-item Hamilton Depression Rating Scales (HAMD). The serum levels of C-reactive protein were dynamically tested after one day, one week, and two weeks after stroke in all patients. Results: The incidence rate of PSD was 36.11%. The hs-CRP levels in stroke groups decreased gradually after one day, one week and two weeks respectively after stroke. The serum levels of hs-CRP were significantly different in a depression-degree-dependent manner among PSD, non-PSD, and control groups, and among PSD groups at different degrees (all P < 0.01). The serum levels of hs-CRP in PSD group had a positive correlation to the average scores of HAMD and ZUNG in one day, one week and two weeks after stroke (P < 0.0001). Conclusion: The change of serum levels of hs-CRP might exist in patients with PSD, and it suggests that PSD might be early diagnosed by dynamically testing the serum levels of hs-CRP.
Article
Background: Acne vulgaris is a common dermatological condition and is known to be caused by many factors. Presence of obesity causes a number of changes in the skin barrier function as well as in lipid profile. Aims & Objective: The objective of this study is to find out the relevance of lipids and lipoproteins levels in obese and non-obese acne patients and compare it with healthy controls. Materials and Methods: 50 obese female subjects with acne (Group-A) along with 50 non-obese female subjects with acne (Group-B) were assessed for BMI (Body Mass Index), serum total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL) and high density lipoproteins (HDL). The results were compared with age matched healthy females who served as controls (Group-C). Results: Highly significant elevations were observed in the values of BMI, TC, TG and LDL in both Group-A & Group-B as compared to group-C (p<0.001). The elevations were more in Group-A as compared to Group-B. The levels of HDL were lower in Group-A and Group-B as compared to Group-C. These parameters were lower in Group-A than in Group-B. Conclusion: Acne vulgaris is definitely associated with changes in lipid profile which are more marked in obese individuals (BMI>27kg/m2 and waist-hip ratio>0.8).The reduction in body weight need to be taken care of while treating acne patients.
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Cardiovascular disease [CVD] is a leading cause of mortality accounting for a global incidence of over 31%. Atherosclerosis is the primary pathophysiology underpinning most types of CVD. Historically, modifiable and non-modifiable risk factors were suggested to precipitate CVD. Recently, epidemiological studies have identified emerging risk factors including hypotestosteronaemia, which have been associated with CVD. Previously considered in the realms of reproductive biology, testosterone is now believed to play a critical role in the cardiovascular system in health and disease. The actions of testosterone as they relate to the cardiac vasculature and its implication in cardiovascular pathology is reviewed.
Article
Even with the well‐recognized benefits of exercise, levels of physical activity are on the decline, while weight gain levels are increasing. The purpose of this evidence‐based literature review was to investigate the relationship between physical fitness, sexual functioning and overall health. There is too little information about these relationships to the detriment of educational programming efforts designed to help protect the public against noncommunicable diseases and their associated individual, family, organization, and societal costs. The literature review revealed that even modest increases in physical activity were positively associated with enhanced sexual functioning. Sexual functioning was also strongly linked to overall health, supporting the usefulness of including sensitively‐presented information about the benefits of exercise and being physically fit as it relates to sexual functioning in adult health education curricula. Gender and age differences, physical self‐concept, and well‐being also emerged as important factors when considering the links between physical fitness, sexual functioning and overall health. Recommendations for research included (a) controlling for possible social desirability effects and (b) designing new research that follows the association between physical activity, sexual functioning and overall health longitudinally in more international settings beyond the U.S. and western Europe.
Article
Depression is the leading cause of disability worldwide, and its prevalence is 2 times higher in women than in men. There is, however, a lack of data on sex-specific pathophysiology of this disorder. The purpose of this systematic review is to identify the biological sex differences found in major depressive disorder (MDD) in studies published in the last 10 years. We conducted a literature search using the Medline, PsycInfo, PubMed, and Web of Science databases, selecting English-language studies that included physiological measures compared by sex in addition to MDD. We identified 20 relevant studies, which consisted primarily of mixed methodology and samples. The reported physiological measures comprised a variety of serum biomarkers, gene mRNA expression, and brain activity. Findings suggest different biological patterns in those with MDD depending on sex. Specifically, women presented higher levels of inflammatory, neurotrophic, and serotonergic markers and a stronger correlation between levels of some inflammatory and neurotrophic factors and the severity of symptoms. This review provides information about possible different biological patterns for women and men with depressive disorder and may have important implications for treatment. Future research should include homogeneous samples; make comparisons based on sex, control sex hormone fluctuations and pharmacological treatment; and use consistent criteria for evaluating psychobiological changes in MDD.
Article
Objectives: To examine the concurrent use of self-report questionnaires and hormonal biomarkers, specifically levels of testosterone and cortisol, along with demographic variables and corrected age (CA) in the assessment of mental health and healthy behaviors among mothers of very-low-birthweight (VLBW, BW < 1,500 g) infants at five time points over 2 years post birth. Method: Data on 40 mothers from a neonatal intensive care unit of a tertiary medical center in the southeast United States were collected from the medical record, standard questionnaires for the mother (depressive symptoms, perceived stress, anxiety, mental health status, parenting stress, and healthy lifestyle behaviors), and biochemical measurement of maternal testosterone and cortisol using enzyme immunoassay at birth, 40 weeks' postmenstrual age, and 6, 12, and 24 months CA. Results: Maternal self-report of mental health improved from birth to 6 or 12 months then worsened at 24 months. Mixed linear models showed that mothers with higher testosterone levels had more depressive symptoms and smoked more, whereas mothers with higher cortisol levels had healthier behaviors and exercised more. Testosterone levels were negatively correlated with cortisol levels. Marital status, education, and health insurance were the most predictive demographic variables for the levels of hormonal biomarkers, mental health, and healthy behaviors. Conclusions: The use of self-report and biochemical measurement was effective in assessing maternal mental health and healthy behaviors over 2 years post birth, when mothers of VLBW infants tend to experience more mental health problems and parenting difficulties than mothers of normal-BW full-term infants.
Article
Background: Adrenal and sex hormone dysregulation have been independently associated with increased depression and anxiety. Cortisol can modify production of sex hormones and hormone-mood associations. This study evaluated associations and interplay of sex and adrenal hormones with depression and anxiety. Methods: We assessed 545 Ecuadorian adolescents (11-17y, 50.4% female, ESPINA) for depression and anxiety symptoms using standardized scales. Testosterone, cortisol, dehydroepiandrosterone (DHEA), and estradiol (boys only) were measured in saliva. We performed logistic regression modeling to calculate odds ratios (OR) of elevated depression or anxiety (scores ≥60) comparing participants with low (<10th percentile) and elevated hormones (≥90th percentile) to normal concentrations (10th-90th percentile). Effect modification by cortisol and testosterone was assessed. Models adjusted for demographic, anthropometric, and circadian measures. Results: In all participants, elevated testosterone (OR [95%CI:]=1.78 [0.98, 3.23]) and cortisol (OR=1.69 [0.95, 2.99]) were marginally associated with elevated anxiety scores. In boys, elevated estradiol was associated with elevated depression (OR=4.75 [1.95, 11.56]) and anxiety scores (OR=2.43 [1.01, 5.84]). In linear regression, estradiol was positively associated with depression (difference/10% hormone increase (β=0.45 [0.15, 0.75]) and anxiety scores (β=0.42 [0.13, 0.72]). Higher cortisol levels strengthened the depression association with estradiol in boys (β=0.54 [0.12, 0.96]), and with testosterone (β= -0.19 [-0.35, -0.03]) and DHEA (β= -0.12 [-0.22, -0.02]) in girls. Testosterone also modified associations. Limitations: This was a cross-sectional analysis. Discussion: Elevated testosterone, cortisol, and estradiol (≥90th percentile) were associated with altered mood. Cortisol and testosterone were considerable effect modifiers to the associations of most hormones with depression and anxiety.
Article
Late life depression (LLD), a familiar syndrome, is not differentiated in the DSM-5. LLD can resemble depressive syndromes in younger adults but it differs in demographic characteristics, phenomenology, prognosis, treatment, suicide risk, relationship to other disorders, and etiology. Older depressed adults often present with fewer major depressive symptoms, less emphasis on mood disturbance, greater preoccupation with somatic or psychotic symptoms, and misleading cognitive deficits. LLD's relationships with medical and neurocognitive symptoms and with inflammatory and immune factors are complex. Formal screening tools and biopsychosocial assessment informs diagnosis and treatment. Evidence supports the effectiveness of lifestyle interventions, several psychotherapies, and a variety of somatic treatment approaches. Comorbid medical disorders must be taken into account when planning treatment. In this article, the authors describe the characteristics of LLD, present an approach to assessment and management, and recommend that future DSM editions include a new specifier to differentiate LLD from other depressive syndromes.
Article
Background Major depressive disorder is the most common neuropsychiatric comorbidity of human immunodeficiency virus (HIV), and women are more frequently affected in the general population and among those with HIV. The rate of depression in HIV is three times higher than the general population. Differences in biomarkers in neuroendocrine and inflammatory pathways are one possible explanation for the increased prevalence of depression in individuals with HIV, especially biological women. Therefore, we aimed to perform a systematic review identifying differences in neuroendocrine factors leading to depression in men versus women with HIV. Methods A comprehensive search of 8 databases was performed, followed by title and abstract screening and later full-text screening by two independent researchers. A risk of bias assessment was completed. Results Twenty-six full-text articles were included in the review. Significant correlations between depression and neuroendocrine marker levels were found for cortisol (both sexes), testosterone (only in men), oxytocin (only tested in women), and estradiol (only in women). No significant correlation between depression and hormone level was found for prolactin, dehydroepiandrosterone (DHEAS), or sex hormone binding globulin (SHBG). Nearly all studies included only men or women and did not directly compare neuroendocrine markers between the two sexes. One study found that the correlation between cortisol levels and depression scores was stronger in women than men. Conclusion Neuroendocrine systems are highly active in the brain and important in the development and persistence of mental illness. Given that HIV can, directly and indirectly, impact hormone signaling, it is likely contributing to the high rate of depression in individuals with HIV. However, few studies explore neuroactive hormones in depression and HIV, nor how this connection may differ between the sexes. More high-quality research is needed in this area to explore the link further and inform possible avenues of treatment.
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Post-menopausal osteoporosis has long been treated and prevented by estrogen replacement therapy (ERT). Despite its effectiveness, ERT is associated with serious adverse effects. Labisia pumila var. alata (LP) is a herb with potential as an alternative agent to ERT due to its phytoestrogenic, antioxidative and anti-inflammatory effects on bone. This study aimed to determine the effects of LP supplementation on bone biomechanical strength of postmenopausal osteoporosis rat model. Ninety-six female Sprague-Dawley rats aged 4 to 5 months old were randomly divided into six groups; six rats in the baseline group (BL) and eighteen rats in each group of; Sham- operated (Sham), ovariectomised control (OVXC) and ovariectomised with daily oral gavages of Premarin at 64.5 μg/kg (ERT), LP at 20 mg/kg (LP20) and LP at 100 mg/kg (LP100) respectively. These groups were subdivided into three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out for biomechanical strength analysis using Instron Universal Model 5848 Micro Tester. OVXC group showed deterioration in the bone biomechanical strength with time. Both ERT and LP supplemented rats showed improvements in bone strength parameters such as maximum load, displacement, stiffness, stress, and Young Modulus. The most improved bone strength was seen in rats given LP at the dose of 100 mg/kg for nine weeks. LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomy-induced bone biomechanical changes.
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This paper describes a biosocial model of status in face-to-face groups. It argues that status ranks are allocated among members of a group through face-to-face interaction and that the allocation process is similar across each primate species, including humans. Every member of a group signifies its rank through physical or vocal demeanor. For example, behavioral signs of dominant status include erect posture, glares, eye contact, strutting, and (in humans) assertive speech. Individuals whose behaviors exhibit dominance show high or rising levels of testosterone compared to those who exhibit deference. Testosterone and dominance are reciprocally related. The model relies more on research on males than on females. It is proposed as a theory about both sexes, but with a caution that little is known about sex differences in the relation of hormones to dominance behavior.
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Context.— Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials.Objective.— To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.Design.— Randomized, blinded, placebo-controlled secondary prevention trial.Setting.— Outpatient and community settings at 20 US clinical centers.Participants.— A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years.Intervention.— Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n=1380) or a placebo of identical appearance (n=1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years.Main Outcome Measures.— The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered.Results.— Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).Conclusions.— During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue. Figures in this Article MANY OBSERVATIONAL studies have found lower rates of coronary heart disease (CHD) in women who take postmenopausal estrogen than in women not receiving this therapy.1- 5 This association has been reported to be especially strong for secondary prevention in women with CHD, with hormone users having 35% to 80% fewer recurrent events than nonusers.6- 12 If this association is causal, estrogen therapy could be an important method for preventing CHD in postmenopausal women. However, the observed association between estrogen therapy and reduced CHD risk might be attributable to selection bias if women who choose to take hormones are healthier and have a more favorable CHD profile than those who do not.13- 15 Observational studies cannot resolve this uncertainty. Only a randomized trial can establish the efficacy and safety of postmenopausal hormone therapy for preventing CHD. The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized, double-blind, placebo-controlled trial of daily use of conjugated equine estrogens plus medroxyprogesterone acetate (progestin) on the combined rate of nonfatal myocardial infarction (MI) and CHD death among postmenopausal women with coronary disease. We enrolled women with established coronary disease because their high risk for CHD events and the strong reported association between hormone use and risk of these events make this an important and efficient study population in which to evaluate the effect of hormone therapy.
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Context While recent pharmacological advances have generated increased public interest and demand for clinical services regarding erectile dysfunction, epidemiologic data on sexual dysfunction are relatively scant for both women and men. Objective To assess the prevalence and risk of experiencing sexual dysfunction across various social groups and examine the determinants and health consequences of these disorders. Design Analysis of data from the National Health and Social Life Survey, a probability sample study of sexual behavior in a demographically representative, 1992 cohort of US adults. Participants A national probability sample of 1749 women and 1410 men aged 18 to 59 years at the time of the survey. Main Outcome Measures Risk of experiencing sexual dysfunction as well as negative concomitant outcomes. Results Sexual dysfunction is more prevalent for women (43%) than men (31%) and is associated with various demographic characteristics, including age and educational attainment. Women of different racial groups demonstrate different patterns of sexual dysfunction. Differences among men are not as marked but generally consistent with women. Experience of sexual dysfunction is more likely among women and men with poor physical and emotional health. Moreover, sexual dysfunction is highly associated with negative experiences in sexual relationships and overall wellbeing. Conclusions The results indicate that sexual dysfunction is an important public health concern, and emotional problems likely contribute to the experience of these problems.
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Context.— Epidemiological studies have established a relationship between cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of ischemic heart disease (IHD), but up to half of patients with IHD may have cholesterol levels in the normal range. Objective.— To assess the ability to predict the risk of IHD using a cluster of nontraditional metabolic risk factors that includes elevated fasting insulin and apolipoprotein B levels as well as small, dense LDL particles. Design.— Nested case-control study. Setting.— Cases and controls were identified from the population-based cohort of the Québec Cardiovascular Study, a prospective study conducted in men free of IHD in 1985 and followed up for 5 years. Participants.— Incident IHD cases were matched with controls selected from among the sample of men who remained IHD free during follow-up. Matching variables were age, smoking habits, body mass index, and alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD cases and controls. Main Outcome Measures.— Ability of fasting insulin level, apolipoprotein B level, and LDL particle diameter to predict IHD events, defined as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary death. Results.— The risk of IHD was significantly increased in men who had elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL particles, compared with men who had normal levels for 2 of these 3 risk factors (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) did not attenuate the relationship between the cluster of nontraditional risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of IHD in men having a combination of elevated LDL-C and triglyceride levels and reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after multivariate adjustment for fasting plasma insulin level, apolipoprotein B level, and LDL particle size. Conclusion.— Results from this prospective study suggest that the measurement of fasting plasma insulin level, apolipoprotein B level, and LDL particle size may provide further information on the risk of IHD compared with the information provided by conventional lipid variables.
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We examine the relationship of testosterone to tendencies to marry and divorce, and to the quality of marriage, of a large representative sample of men. The analysis shows that men producing more testosterone are less likely to marry and more likely to divorce. Once married they are more likely to leave home because of troubled marital relations, extramarital sex, hitting or throwing things at their spouses, and experiencing a lower quality of marital interaction. Sociological models that might be informed by this finding are examined, and its implications for subsequent research are discussed.
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This article describes an interim safety analysis of an ongoing 2-year, double-blind study to compare two doses of estrogen-androgen therapy (0.625 or 1.25 mg esterified estrogens combined with 1.25 mg or 2.5 mg methyltestosterone, respectively) with two doses of conjugated estrogens (0.625 mg or 1.25 mg conjugated equine estrogens) in 291 surgically menopausal women. Except for an excess of nausea in the estrogen-only group, reported adverse events (headache, breast pain, weight increase, vaginitis, and hirsutism) did not differ significantly between groups. The majority of adverse events were manifest by 6 months and were not dose related. Only four estrogen-androgen and two conjugated estrogen participants reported hirsutism as an adverse event, but Ferriman-Gallwey evaluations at 12 months detected increased hair growth in 14%-22% of women in each treatment group, with a slight but nonsignificant increment in the higher dose estrogen-androgen group. No significant differences between groups for weight increase or blood pressure were observed at 6 or 12 months. At 6 and 12 months, decreases in triglycerides and HDL cholesterol were observed for both doses of estrogen-androgen, whereas increases were observed in women assigned to conjugated estrogen. Total cholesterol and LDL decreased in all treatment groups by 6 months. No adverse effects on serum creatinine or liver function tests were observed-in any treatment group. These results demonstrate that estrogen therapy in combination with androgens is generally as well tolerated as estrogen therapy alone for at least 1 year of treatment. The clinical implications of the more frequent nausea and higher triglycerides with unopposed estrogen and of the lower HDL cholesterol levels with estrogen-androgen treatment are unknown.
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Men with higher levels of serum testosterone have lower-status occupations, as indicated by archival data from 4,462 military veterans in six U.S. census occupational groups. This finding supports a structural equation model in which higher testosterone, mediated through lower intellectual ability, higher antisocial behavior, and lower education, leads away from white-collar occupations. The model is plausible because testosterone levels are heritable and available early enough to affect a number of paths leading to occupational achievement. Prior research has related testosterone to aggression in animals and men, and high levels of testosterone presumably evolved in association with dominance in individual and small-group settings. It appears an irony of androgens that testosterone, which evolved in support of a primitive kind of status, now conflicts with the achievement of occupational status.
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OBJECTIVES The study examined arterial and cardiac structure and function in bodybuilders using androgenic anabolic steroids (AAS), compared to non-steroid-using bodybuilder controls.BACKGROUND Adverse cardiovascular events have been reported in bodybuilders taking anabolic steroids. The cardiovascular effects of AAS, however, have not been investigated in detail.METHODS We recruited 20 male bodybuilders (aged 35 ± 3 years), 10 actively using AAS and 10 who denied ever using steroids. Serum lipid and hormone levels, carotid intima-media thickness (IMT), arterial reactivity, and left ventricular (LV) dimensions were measured. Vessel diameter was measured by ultrasound at rest, during reactive hyperemia (an endothelium-dependent response, leading to flow-mediated dilation, FMD), and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). Arterial reactivity was also measured in 10 age-matched non-bodybuilding sedentary controls.RESULTSUse of AAS was associated with significant decreases in high density lipoprotein cholesterol, sex hormone binding globulin, testosterone and gonadotrophin levels, and significant increases in LV mass and self-reported physical strength (p < 0.05). Carotid IMT (0.60 ± 0.04 mm vs. 0.63 ± 0.07 mm), arterial FMD (4.7 ± 1.4% vs. 4.1 ± 0.7%) and GTN responses (11.0 ± 1.9% vs. 14.4 ± 1.7%) were similar in both bodybuilding groups (p > 0.2). The GTN responses were significantly lower and carotid IMT significantly higher in both bodybuilding groups, however, compared with the non-bodybuilding sedentary controls (p = 0.01).CONCLUSIONS Although high-level bodybuilding is associated with impaired vascular reactivity and increased arterial thickening, the use of AAS per se is not associated with significant abnormalities of arterial structure or function.
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The most appropriate treatment for intersex children remains a topic of debate, in part because of a lack of knowledge about the medical, operative, and psychosexual outcomes in affected adults. This study examined outcomes in 14 women diagnosed as having complete androgen insensitivity syndrome (CAIS). Women with CAIS provide an excellent opportunity to study the effects of estrogen on gender development in 46,XY individuals who are unresponsive to androgens. CAIS was diagnosed if testes were present along with normal external female genitalia in a 46,XY person, an androgen receptor gene mutation was identified, there was spontaneous feminization at puberty except for a lack of menses, virilization was not evident despite normal or high male testosterone levels, and axillary and pubic hair was much reduced or absent postpubertally. The women ranged in age from the late 20s to mid-60s when evaluated (average, 45 years). Eight participants, 57% of the total, were at or above the 90th centile of control adult female height; the others were between the 50th and 75th centiles. Seven women exceeded ideal body weight by at least 15 kg, three of them by 80 kg or more. Most gonadectomies and vaginoplasties had been performed in adolescence or adulthood. Eight subjects, one a homosexual, did not require vaginoplasty. In no case was clitoroplasty necessary. Bone loss was documented in 43% of women. More than 80% had received some form of counseling. Nearly 80% of subjects were satisfied with their genitalia with regard to sexual function. A majority estimated their libido as being average or stronger. Ten of 13 reported being able to experience organisms. Only 1 of 14 women was substantially dissatisfied with her physical appearance, although 5 others were somewhat dissatisfied. In general, these women perceived themselves as being feminine throughout their development and had experienced female fantasies and experiences since adolescence. Half of the women were married at the time of the study. Five of them and one unmarried women had adopted children. Without exception the women were satisfied with their gender assignment. These women with CAIS have had generally satisfactory medical, surgical, and psychosexual outcomes. All of them were pleased at having been raised as females, and none desired gender reassignment.
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Using a large sample of men, we examine alternative models of the way in which testosterone may influence adult deviant behavior. The results indicate a significant and moderately strong relationship between testosterone and adult deviance, and this relationship between testosterone and adult deviance is largely mediated by the influence of testosterone on social integration and on prior involvement in juvenile delinquency. In addition, testosterone level moderates the relationship of social integration to adult deviance: The restraining influence of social integration is less necessary for men with lower levels of testosterone. Further, prior delinquency interacts with social integration in the same fashion, accounting for much of the moderating effect of testosterone. This pattern of results supports the conclusions that (1) testosterone is one of a larger constellation of factors contributing to a general latent propensity toward deviance and (2) the influence of testosterone on adult deviance is closely tied to social factors. Our findings show that there is considerable promise in a biosocial approach that integrates social and biological explanations, rather than playing them off against one another.
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Hyperactivity of the HPA–system in major depression is reflected by an increased secretion of adrenal hormones especially cortisol and dehydroepiandrosterone (DHEA). In women for whom androgenicity is associated with cardiovascular disorders the dominant source of androstenedione and testosterone secretion are the adrenal glands. To date, there is only sparse information about the regulation of androstenedione, testosterone and dihydrotestosterone (DHT) concentrations in women with severe major depression.
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Testosterone replacement therapy is an effective treatment of some depressive symptoms in hypogonadal men, and may be an effective augmentation treatment for SSRI-refractory major depression in such men. We treated five depressed men who had low testosterone levels and had not responded to an adequate SSRI trial with 400 mg testosterone replacement biweekly for 8 weeks. Four patients underwent single-blind placebo discontinuation. Patients were assessed at baseline and biweekly thereafter using the Hamilton Depression Rating Scale (HAM-D) and the Endicott Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q). Patients' mean age was 40 years, and mean testosterone level 277 ng/dl. All had a rapid and dramatic recovery from major depression following testosterone augmentation: mean 21-item HAM-D decreased from 19.2 to 7.2 by week 2, and to 4.0 by week 8; mean Q-LES-Q increased from 45% to 68%. Three of four subjects who underwent discontinuation of testosterone under single-blind placebo treatment began to relapse. Testosterone replacement therapy may be an effective treatment of depressive symptoms in some men, and warrants further research.