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ORIGINAL ARTICLE: The Current Outlook for Testosterone in the Management of Hypoactive Sexual Desire Disorder in Postmenopausal Women

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Abstract

Hypoactive sexual desire disorder (HSDD) is a common clinical problem in women, especially those who have experienced surgical menopause. Because androgen levels decline with age and drop dramatically following bilateral oophorectomy, it has been hypothesized that reduced levels of testosterone are related to diminished desire. As presented at a continuing medical education satellite symposium during the 2008 annual meeting of the International Society for the Study of Women's Sexual Health, to review the current state of knowledge about the physiologic effects of testosterone in postmenopausal women, the effects of transdermal testosterone delivery in surgically menopausal women with HSDD, and ongoing studies of a transdermal testosterone gel. A review of the pertinent literature, including recent presentations. Results from the Women's International Study of Health and Sexuality; and studies utilizing the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and validated instruments that assess female sexual function: the Sexual Activity Log, the Profile of Female Sexual Function, and the Personal Distress Scale. Surgically menopausal women receiving testosterone experience significant increases in total satisfying sexual activity vs. women receiving placebo, significant improvement in all domains of sexual function, and decreases in personal distress, with a favorable safety profile. Testosterone deficiency may be considered among the underlying causes of HSDD. Currently, testosterone is available to women in the United States only via off-label prescribing or by unregulated compounding of testosterone preparations. New safety trials will examine the long-term safety of testosterone gel in surgically menopausal women with HSDD who are at high risk of cardiovascular disease or breast cancer.

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... In contrast, some researchers have suggested that high income level is related to lower sexual satisfaction [19]. Moreover, some studies have suggested that androgens, but not FSH, play an important role in libido and sexual arousal [20][21][22], but other studies have not supported this hypothesis, and instead emphasized physiologic ovarian failure in hormone secretion [23,24]. We also found a, b, c, d, e and f are represent the patients with the highest scores on the modified FSFI score system. ...
... A small decline in TT level has been reported in NM, while in SM, TT significantly decreased [25]. Some studies have suggested that androgens play an important role in libido and sexual arousal [20][21][22]. Supporting these studies, we found that higher serum DHEA-S concentrations increase the frequency of sexual desire, and higher serum TT concentrations increase coital frequency, but lower serum FSH concentrations increase the frequency of sexual arousal. However, some investigations have not supported this hypothesis, and emphasized physiologic ovarian failure in hormone secretion [23,24]. ...
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Article
Background: The aim of this study was to investigate factors affecting the sex lives of middle-aged women, and whether surgical menopause affects sexual function differently from natural menopause, by comparing effects on sexual performance of women with similar demographic features. Material/Methods: The study included 151 women with surgical menopause (SM), 357 women with natural menopause (NM), and 186 perimenopausal women (PM). The women were asked to complete a 6-question survey of sexual performance parameters. The relationship between the demographic and clinical features and hormone levels of the groups and sexual function parameters were evaluated. We also compared these parameters between the 3 study groups, and paired comparisons were made between the SM group and the NM group. Results: Demographic features, serum DHEA-S, total testosterone, and FSH levels were found to have statistically significant effects on sexual performance of women (p<0.05). The sexual function scores for the frequency of sexual desire, coitus, and orgasm were significantly higher in the PM group, whereas vaginal lubrication scores were lower compared to the NM and SM group (p<0.05). In paired comparison of NM and SM, the scores for the frequency of coitus, orgasm, and vaginal lubrication were significantly higher in the SM group, while sexual desire frequency scores were higher in the NM group (p<0.05). Conclusions: Our study approached to this topic in an extended manner and found significant relationships between several demographic-clinical and hormonal factors. SM was found to not affect female sexual performance, except for sexual desire, more than NM.
... Higher T doses have been shown to correlate with greater improvement in quality of life as evidenced by the 'Menopause Rating Scale' total score and somatic, psychological and urogenital sub-scores [5]. This is consistent with other studies reporting that T effect is dose dependent [18,222324. In addition, these T implant doses have been shown to increase scalp hair growth and were not associated with androgenic alope- cia [8]. ...
... Contrarily, there is no clinical evidence supporting the recommendation that 'serum levels of T on therapy should remain within the upper limits of endogenous production for a young healthy female'. This theoretical 'physiologic dosing' of T in women has been shown to be clinically ineffective [18,24,28]. The simplistic concept of using a single serum T level to guide therapy ignores the complexity of physiologic events from production/release to biological effect; and totally disregards the significant contribution of local production, as well as, age related changes. ...
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Article
Objectives: The objectives of this study were to determine therapeutic serum testosterone (T) levels/ranges and inter-individual variance in women treated with subcutaneous T implants. Study design: In study group 1, T levels were measured at two separate time intervals in pre- and post-menopausal women treated with subcutaneous T for symptoms of androgen deficiency: (i) four weeks after pellet insertion, and (ii) when symptoms of androgen deficiency returned. In a separate pharmacokinetic study (study group 2), 12 previously untreated postmenopausal women each received a 100mg T implant. Serum T levels were measured at baseline, 4 weeks and 16 weeks following T pellet implantation. In study 'group' 3, serial T levels were measured throughout a 26 h period in a treated patient. Results: In study group 1, serum T levels measured at 'week 4' (299.36±107.34 ng/dl, n=154), and when symptoms returned (171.43±73.01 ng/dl, n=261), were several-fold higher compared to levels of endogenous T. There was significant inter-individual variance in T levels at 'week 4' (CV 35.9%) and when symptoms returned (CV 42.6%). Even with identical dosing (study group 2), there was significant inter-individual variance in T levels at 'week 4' (CV 41.9%) and 'week 16' (CV 41.6%). In addition, there was significant intra-individual circadian variation (CV 25%). Conclusions: Pharmacologic dosing of subcutaneous T, as evidenced by serum levels on therapy, is needed to produce a physiologic effect in female patients. Safety, tolerability and clinical response should guide therapy rather than a single T measurement, which is extremely variable and inherently unreliable.
... HSDD has been hypothesized to occur due to low circulating androgen levels arising from either post-menopause or surgical removal of the ovaries [36,37]. Currently, data support that testosterone treatment shows efficacy in women with low levels and a decrease in sexual desire [38][39][40][41][42][43]. Likewise, combination therapy of estrogen and methyltestosterone has been shown to be a viable treatment for HSDD. ...
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Article
Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.
... The use of androgens for improving the sexual function of postmenopausal women has been studied. It has been shown that various types of prescriptions of testosterone (oral, intramuscular injections, and subcutaneous implants) are associated with an increase in sexual desire among postmenopausal women (Kingsberg, Simon, & Goldstein, 2008). Some studies have shown that the addition of testosterone to estradiol prescriptions remarkably improves sexual function (Davis, McCloud, Strauss, & Burger, 1995;Lobo, Rosen, Yang, Block, & Van Der Hoop, 2003). ...
Article
Objectives: This study aimed to narratively summarize the effects of serum androgens on sexual function of postmenopausal women and the impact of administration of various types of androgens in improving the sexual function of these women. Methods: After searching for articles indexed in various databases, a total of 59 studies were selected. Results: There appears to be a great deal of controversy regarding the relationship between androgens and sexual function and the beneficiary effect of androgens therapy. Conclusions: Androgens may affect sexual function; however, androgen therapy, as an option for improving sexual function in menopause, needs further research.
... Kingsberg et al 25 conduziram uma revisão da literatura, publicada em 2008, que mostrou que as mulheres em menopausa cirúrgica que receberam testosterona melhoraram significativamente a sua função sexual comparativamente com o placebo, com um perfil de segurança favorável. Referem, tal como a nossa revisão, que são necessários novos estudos de longa duração para determinar a segurança a longo prazo da testosterona, sobretudo no que respeita aos eventos cardiovasculares e cancro da mama. ...
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Article
Introdução: A disfunção sexual feminina é um problema comum que atinge mais de 1/3 das mulheres em alguma fase da vida. O objetivo deste trabalho é rever a evidência existente acerca da eficácia da testosterona na disfunção sexual, em particular na melhoria do desejo, em mulheres pós-menopáusicas. Material e Métodos: Pesquisa nas bases de dados National Guidelines Clearinghouse, Guidelines Finder, The Cochrane Library e MEDLINE/PubMed, de normas de orientação clínica, revisões sistemáticas, meta-análises e ensaios clínicos aleatorizados e controlados, publicados entre janeiro de 2005 e fevereiro de 2017, utilizando os termos MeSH ‘testosterone’, ‘androgens’, ‘libido’, ‘sexual dysfunctions’ e ‘menopause’. Resultados: Foram incluídos 11 artigos de uma pesquisa inicial de 506: três normas de orientação clínica, uma revisão sistemática com meta-análise e sete ensaios clínicos aleatorizados e controlados. Os artigos selecionados mostraram eficácia da terapêutica com testosterona, em monoterapia ou em associação com outras hormonas, na melhoria global da função sexual e na melhoria do desejo sexual em mulheres na pós-menopausa. Nenhum dos estudos evidenciou alterações das enzimas hepáticas ou efeitos adversos graves. Discussão: Os estudos incluídos tinham amostras de pequenas dimensões e período de follow-up curto, o que impossibilitou a avaliação dos efeitos a longo prazo do tratamento com testosterona. Conclusão: A terapêutica com testosterona tem benefício, a curto prazo, na melhoria das queixas de disfunção sexual em mulheres pós-menopáusicas, em particular na melhoria do desejo. Contudo, são necessários estudos com amostras de maior dimensão e período de follow-up mais longo, de modo a avaliar a sua efetividade e segurança a longo prazo.
... Many systematic reviews were examined to determine pre-existing notions regarding the relationship between TT therapy and breast cancer incidence in treating hypoactive sexual desire disorder in postmenopausal women (25)(26)(27)(28)(29)(30)(31)(32)(33). There is clearly a need to further investigate any potential safety risks related with the use of transdermal testosterone, particularly by using randomised prospective trials. ...
Article
Background/Aim: Hypoactive sexual desire disorder (HSDD) is hypothesised to manifest in postmenopausal women at onset of menopause due to decreased oestrogen levels. Transdermal testosterone is a potential treatment option. This systematic review explores the relationship between the incidence of breast cancer and transdermal testosterone use. Materials and Methods: Searches were conducted on the PubMed and Ovid databases. In Ovid, the advanced search function was used: ‘transdermal testosterone not male’. In PubMed, the following search terms were used: ‘transdermal, testosterone, menopausal, women, breast cancer, women’. Abstracts that fitted our initial criteria were further investigated. Results: A total of 25 publications from PubMed and 192 publications from Ovid were initially assessed. Three randomised control trials were judged to have sufficiently met our inclusion criteria. However, these trials were too heterogeneous for a meta-analysis. A systematic review was deemed the most appropriate analysis of the data available. Conclusion: The publications examined in this systematic review suggest that the use of transdermal testosterone to treat HSDD in postmenopausal women does not increase breast cancer incidence. However, further research in the form of adequately powered randomised controlled trials with breast cancer incidence being the primary end point is required in order to confirm this. © 2018 International Institute of Anticancer Research. All rights reserved.
... [29] In this regard, research has shown that a sexual partner's emotional and physical problems and the resultant unresponsive relationship between the couple were the factors causing sexual dysfunction. [30] Similarly, in the present study, most individuals at the time of menopause reported a lower score in sexual function than the cutoff point, and were dissatisfied with their sexual activity. However, depression, anxiety, and stress were not strong predictors of sexual dysfunction. ...
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Article
Background: Menopause is associated with decreased sexual activity and a feeling of decreased attractiveness and sexual potency. This study tested the hypothesis that sexual health in postmenopausal women is not the same as nonmenopausal women with regard to symptoms of stress, anxiety, and depression. Materials and methods: This cross-sectional study was conducted in 12 health centers in Shiraz between April and September 2015; 310 postmenopausal women included by convenient sampling. Data were collected through the Female Sexual Function Index, and depression anxiety stress scale 21 questionnaires. Analysis performed using SPSS version 22 and included descriptive statistics, Chi-square or Fisher's exact test, and Pearson correlation and linear regression; p < 0.05 was considered statistically significant. Results: The percentage of women with sexual dysfunction in the present study was 88.7%. There was a significant relationship between stress (p = 0.04), anxiety (p = 0.01), and sexual dysfunction. Furthermore, there was a statistically significant relationship between depression (p = 0.003) and sexual dysfunction. Pearson correlation coefficient showed that there was an inverse relationship among stress (-0.24), anxiety (-0.25), depression (-0.30), and sexual function. In addition, linear regression results showed that depression was the most important factor in the description of sexual dysfunction. Conclusion: This study showed that there is an association of the status of mental health and sexual function in post-menopausal women. However, more studies should be carried out to find the confounders.
... 75 The availability of transdermal testosterone for women is limited to unregulated formulations and off-label use of products intended for men, which can lead to higher than normal androgen levels and androgen-related side effects. 80 Decrease in estrogen levels, as typically occurs during the menopausal transition, has been associated with vulvovaginal atrophy and sexual dysfunction. 86 A systematic review and meta-analysis of randomized controlled trials found a positive association between hormone therapy (estrogen alone or in combination with progestogens) and improvement in sexual function in women with menopausal symptoms or in early menopause. ...
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Article
Introduction: Hypoactive sexual desire disorder (HSDD) often has a negative impact on the health and quality of life of women; however, many women do not mention-let alone discuss-this issue with their physicians. Providers of gynecologic services have the opportunity to address this subject with their patients. Aim: To review the diagnosis and evidence-based treatment of low sexual desire in women with a focus on strategies that can be used efficiently and effectively in the clinic. Methods: The Medline database was searched for clinically relevant publications on the diagnosis and management of HSDD. Results: HSDD screening can be accomplished during an office visit with a few brief questions to determine whether further evaluation is warranted. Because women's sexual desire encompasses biological, psychological, social, and contextual components, a biopsychosocial approach to evaluating and treating patients with HSDD is recommended. Although individualized treatment plan development for patients requires independent medical judgment, a simple algorithm can assist in the screening, diagnosis, and management of HSDD. Once a diagnosis of HSDD has been made, interventions can begin with office-based counseling and progress to psychotherapy and/or pharmacotherapy. Flibanserin, a postsynaptic 5-hydroxytryptamine 1A agonist and 2A antagonist that decreases serotonin levels and increases dopamine and norepinephrine levels, is indicated for acquired, generalized HSDD in premenopausal women and is the only agent approved in the United States for the treatment of HSDD in women. Other strategies to treat HSDD include using medications indicated for other conditions (eg, transdermal testosterone, bupropion). Bremelanotide, a melanocortin receptor agonist, is in late-stage clinical development. Conclusions: Providers of gynecologic care are uniquely positioned to screen, counsel, and refer patients with HSDD. Options for pharmacotherapy of HSDD are currently limited to flibanserin, approved by the US Food and Drug Administration, and off-label use of other agents. Clayton AH, Kingsberg SA, Goldstein I. Evaluation and Management of Hypoactive Sexual Desire Disorder. Sex Med 2018;X:XXX-XXX.
... A figure of choices is available for treating vaginal dryness, including the prescription of topical estrogen cream, to be put on several times a workweek [21]. Testosterone administration in early studies included oral, intramuscular injection, and subcutaneous implants, all of which resulted in increases in sexual desire in postmenopausal women [22]. • Medication: The use of non-hormonal moisturizing gel for treating vaginal dryness. ...
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Article
Traditionally, the “elderly” are believed to be those individuals age 65 and older. People ages 65-74 years referred to as the "young-old," persons ages 75-84 years as "old," and persons ages 85 years and older as the "old-old". Research on sexuality in the elderly is still rather infrequent. Many older adults are sexually active. Adult females are less likely than humans to have a spousal or other intimate relationship and to be sexually active. Sexual problems are frequent among older adults, but these problems are infrequently discussed with doctors. Others consider that sexual activity in long-term care facilities is against the rules.
... Transdermal delivery avoids first-pass hepatic metabolism and consistent levels of T [100] can be achieved. Earlier testosterone patch studies included 75 surgically induced menopausal women 31-56 years of age using oral estrogen therapy, with a previously satisfying sex life who reported impaired sexual function following surgery. ...
Chapter
Testosterone production in women across their lifespan, as well as transport, measurement, and metabolism are reviewed. Testosterone directly influences sexuality, mood, body composition, skin and hair, mebonian glands in the eyes, as well as acts on the hematologic and immune system. Bone and cardiovascular system effects are at least in part mediated through aromatization to estrogens. Evaluation and morbidity of testosterone excess syndromes such as polycystic ovary syndrome (PCOS) and androgen secreting tumors are described. Presently, androgen deficient syndrome in women is not acceptable, situations with lower testosterone such as Turner Syndrome, premature ovarian failure, and bilateral oophorectomy carry an increased morbidity and mortality risk. Trials have demonstrated short-term effects of pharmacological, not physiological, levels of testosterone in women. Long-term safety is unknown.
... The combined oral contraceptive pill may be appropriate for some women but effects on BMD are less favourable (Crofton et Adequate estrogen replacement is regarded as a starting point for normalizing sexual function. Local estrogen may be required to treat dyspareunia (Sarrel, 1987;Rubinow et al., 1998;Pacello et al., 2013) C Women with POI should receive adequate counselling about the possibility of using testosterone supplementation so that they can make an informed choice, in the knowledge that long-term efficacy and safety are unknown (Alexander et al., 2004;Kingsberg et al., 2008) B What treatments are available for genito-urinary symptoms in POI? ...
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Article
STUDY QUESTION What is the optimal management of women with premature ovarian insufficiency (POI) based on the best available evidence in the literature?
... Hormone-related libido changes during menopause may be ascribed more to falling testosterone levels than to reduced estrogen levels [18]. Decreased testosterone levels in menopausal women are associated with a loss of sexual desire and sexual pleasure, feelings of diminished physical well-being, and persistent fatigue [19]. Before menopause, the ovaries, as well as the adrenals, produce about 50% of the circulating testosterone and the rest is from the peripheral conversion of precursors derived from the ovary and the adrenals. ...
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Article
Menopause is a natural critical period of every woman's life that is usually associated with physical, behavioral, and psychological changes. This review article aimed to highlight female sexual changes that could take place during such period. A review of the already published articles in this context was carried out using PubMed, Medical Subject Headings (MeSH) database, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Scopus engine until March 2015. The following keywords were used to assess exposure, outcome, and estimates for concerned associations: menopause; sex; female sexual dysfunction; libido; behavior; menopause; postmenopause, humans, and aging. Most studies on this subject correlated hormonal changes during this period with significantly decreased domains of female sexual functions, such as desire, arousal, satisfaction, orgasm, lubrication, and experiencing coital pains. Fortunately, many scientists have taken efforts to alleviate these disorders using emerging treatment methods, topical remedies, and suggested alternative medicament. Significant decreases in female sexual domains are experienced during the postmenopausal period. However, proper counseling, explanations, specific AQ3 remedies and partner guidance are helpful in overcoming female sexual changes during this period.
... Androgens are thought to be essential for libido, sexual arousability, and pleasure, and to play a role in vaginal and clitoral function during genital sexual arousal [7,26]. It has been hypothesized that androgen levels declining with age and dropping dramatically following bilateral oophorectomy might cause sexual desire to diminish [27]. However, this hypothesis seems to be weak [7,28]. ...
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Article
Hysterectomy is the most common major gynecologic operation, together with bilateral salpingo-oophorectomy in the majority of women over the age of 45. To investigate whether surgical menopause affects female sexual performance differently from natural menopause. The study included 121 women who had undergone surgical menopause and 122 women who had undergone natural menopause. All the women had similar economic, sociocultural, and personal demographic profiles, had been postmenopausal for at least 1 year, and were between the ages of 45 and 65. The women were asked to complete a six-question survey of sexual performance parameters (sexual desire, coital frequency, arousal, orgasm frequency, dyspareunia, and vaginal lubrication). These sexual performance parameters were compared between the surgical and natural menopause groups. With the exception of vaginal lubrication, sexual performance parameters were not statistically different between the two groups (P > 0.05). Vaginal lubrication in the surgically menopausal group was lower than in the naturally menopausal group (P < 0.05). Serum dehydroepiandrosterone sulphate, prolactin, and thyrotropin levels were not statistically different between the groups (P > 0.05), whereas serum estradiol and total testosterone levels in the surgically menopausal group were lower than those of the naturally menopausal group (P < 0.05). The results of this study showed that surgical menopause did not affect female sexual performance differently from natural menopause, with the exception of vaginal lubrication. Kokcu A, Kurtoglu E, Bildircin D, Celik H, Kaya A, and Alper T. Does surgical menopause affect sexual performance differently from natural menopause? J Sex Med **;**:**-**. © 2015 International Society for Sexual Medicine.
... 161 After reviewing the data from the clinical trials of TTP in postmenopausal women, the committee accepted the efficacy of TTP but deemed the safety data inadequate. 162 As result of this decision, the new drug application was withdrawn in the United States. It was subsequently submitted to and approved in the European Union but has recently been discontinued by the company that markets it. ...
Article
This review aims to describe low sexual desire (1) as a construct within theoretical models of female sexual response, (2) as a sexual disorder with evolving or competing nosology between the DSM-IV-TR and the DSM 5, and (3) as a clinical condition that healthcare providers need to manage, and the current status of treatment options. We conducted a literature review of the epidemiology, diagnosis, and treatment of low sexual desire/hypoactive sexual desire disorder (HSDD). The prevalence rate of low sexual desire is high, reaching 43%, whereas that of HSDD comes close to 10%. The DSM 5 categories of female sexual disorders include female sexual interest/arousal disorder, which is a combination of the DSM-IV-TR disorders HSDD and female sexual arousal disorder. Treatment paradigms vary and are individualized based on the biopsychosocial components of desire that are compromised in a woman. The two primary approaches to treating HSDD are psychotherapy/sex therapy (individual or couples) and pharmacotherapy. To date, there are no Food and Drug Administration-approved pharmacologic treatments. However, four investigational drugs are in mid- to late-stage clinical trial development. Low sexual desire is the most prevalent sexual problem in women and should be assessed and treated by healthcare professionals. Currently, there are only modest evidence-based nonpharmacologic treatment options and no approved pharmacologic options. Despite these treatment limitations, healthcare providers can address many of the sexual health concerns of women.
... In recent years, testosterone (T) has gained attention as a potential treatment for women with hypoactive sexual desire disorder. [1][2][3][4][5][6][7] Although still controversial, especially with regard to its long-term effects, T treatment both administered alone or in combination with classic hormone replacement therapy, has been shown to provide a small, but significant improvement in different aspects of sexual function, such as sexual interest, genital sensation, orgasmic response and sexual satisfaction. 8 Genital sexual arousal results from the synergy of both central and peripheral mechanisms. ...
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Article
To date, the effects of long-term testosterone (T) administration on the human vagina are not completely understood. Thus, the aim of this study was to investigate the effects of long-term T treatment on vaginal tissue histology, estrogen receptor alpha (ERα) and beta (ERβ) expression and proliferation in female to male transsexual subjects (FtM). We compared vaginal samples from FtM subjects with those of premenopausal women (PrM) and postmenopausal women (M) not receiving any hormonal treatment for at least 2 years. Vaginal tissue samples from 16 FtM subjects treated with T (intramuscular injections of 100 mg Testoviron Depot/7-10 days for at least 1 year), undergoing sex reassignment surgery, and 16 PrM and 16 M subjects undergoing a vaginal hysterectomy for prolapse, were collected. For each sample, morphology, glycogen content, proliferation (ki-67), ERα and ERβ expression were evaluated. Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted. T administration resulted in a strong proliferation reduction when compared with both M and PrM subjects. Stromal and epithelial ERα as well as ERβ were significantly decreased in FtM when compared with PrM subjects. In conclusion, our data suggests that systemic T administration at supraphysiological dosage, determines profound changes in histomorphology and reduces ERs expression and proliferation of vaginal epithelium.International Journal of Impotence Research advance online publication, 4 April 2013; doi:10.1038/ijir.2013.9.
... This difference has been attributable to the fact that, during natural menopause, the production of testosterone continues, although at a much reduced rate, while surgical menopause causes a dramatic and definite cessation of androgen production. During surgical menopause, androgen levels drop to less than 50% of the normal production of testosterone in naturally menopausal women (for a review, see [86]). However, the changes in the sexual cycle caused by oophorectomy are quite pervasive and have been found to affect all aspects of sexual function, including sexual arousal, orgasm, and pain [84], and therefore it is difficult to identify whether the low desire is exclusively the product of the changes that affected the entire cycle or if there is a direct effect on desire per se. ...
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Chapter
Hypoactive Sexual Desire Disorder (HSDD) is diagnosed when an individual indicates persistent or recurrent blunted levels of sexual desire and/or a lack of sexual fantasies that cause marked distress and/or interpersonal difficulties [1]. This diagnosis is intended to include only individuals who experience dissatisfaction with their low levels of sexual desire. Women with this condition will often report that they “want to want” more sex, while women with low levels of sexual desire that do not meet HSDD criteria will indicate no bother or concerns with the frequency of their sexual desire. The subjective experience of distress caused by low desire is a critical component of the diagnosis of HSDD because many individuals are not alarmed by low levels of sexual desire. Indeed, an epidemiological study conducted in Australia demonstrated that 32% of women who are 20–70 years old report low sexual desire, but only 16% report distress caused by the low sexual desire [2]. KeywordsDesire-libido-HSDD-questionnaires-FSFI
... In women, circulating testosterone levels decreases with age and can attain levels that are below median values for women in their twenties [4]. In recent years, there has been an interest in the clinical use of the testosterone transdermal patch as a hormone replacement therapy for women who are unresponsive to estrogen treatment to manage fatigue, loss of well-being, and reduced libido [5][6][7][8][9]. ...
Article
The purpose of this study was to provide a quantitative assessment of female rat sexual behaviors after acute exposure to the A-ring reduced testosterone metabolite, androstanediol (3α-Diol), through the nucleus accumbens (NA) shell. Quantitative analyses of female rat sexual behaviors and assessment of protein levels for the enzyme glutamic acid decarboxylase isoform 67 (GAD67) and gephyrin, a protein that participates in the clustering of GABA-A receptors in postsynaptic cells, were accomplished. Female rats were ovariectomized and primed with estrogen and progesterone to induce sexual behaviors. Females received a 3α-Diol infusion via guided cannula that aimed to the NA shell five minutes prior to a sexual encounter with a stud male. The following parameters were videotaped and measured in a frame by frame analysis: lordosis quotient (LQ), Lordosis rating (LR), frequency and duration of proceptive behaviors (hopping/darting and ear wiggling). Levels of GAD67 and gephyrin were obtained by Western blot analysis two or twenty-four hours after the sexual encounter. Acute exposure to 3α-Diol in the NA shell enhanced LR, ear wiggling, and hopping/darting but not LQ. Some of these behavioral effects were counteracted by co-infusion of 3α-Diol plus the GABAA-receptor antagonist GABAzine. A transient reduction of GAD67 levels in the NA shell was detected. The testosterone metabolite 3α-Diol enhances sexual proceptivity, but not receptivity, when infused into the NA shell directly. The GABAergic system may participate in the androgen-mediated enhancement of female rat sexual motivation.
... This patient had a normal hormonal profile, an important factor that contributes to a normal sexual response (da Silva et al., 2009;Kingsberg, Simon, & Goldstein, 2008;van Anders, Brotto, Farrell, & Yule; thus, sexual dysfunction in this case may have been to the result of the anatomical defect, and culminated in coital pain, and thus psychological problems (Boul, Hallam-Jones, & Wylie, 2009;Brauer, ter Kuile, Laan, & Trimbos, 2009). Hence, beyond anatomical problems, this patient was at risk for the most common causes of sexual dysfunction related to factors such as sexual repression, dyadic factors, culture, and religious orthodoxy (Boul et al.;De Cecco & Elia, 1993;Ruether, 2000;Roach, 2004) that motivate negative feelings about sexuality. ...
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Article
Vagina agenesis is a rare entity. Mayer-Rokitansky-Kuster-Hauser syndrome is the most significant cause of vagina agenesis, whereas the second most common cause is complete androgen syndrome. Surgical treatment can propitiate a vaginal reconstruction, but sexual function depends on several factors that affect sexual performance. Many reports focus on the intraoperative and postoperative results and only describe the global approach to these patients, but reports focusing on the management of these patients to enable them to have a normal sexual life are lacking. This case report highlights a multidisciplinary treatment for this kind of morbidity and emphasizes the necessity of incorporating careful attention to sexual health in the treatment of these patients so that they may achieve a good therapeutic response, resulting in a pleasurable sexual life and a good quality of living.
... A recent study has shown that female sexual arousal disorder is of a common occurrence and it has been reported by up to 26% of American women [8]. Despite its high prevalence, the present pharmacological treatment modalities for female sexual dysfunctions are limited [9][10][11]. Androgens primarily affect sexual desire, arousal, orgasm, and the overall sense of well-being. ...
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Article
Yoga is a popular form of complementary and alternative therapy. It is practiced both in developing and developed countries. Female sexual dysfunctions are common and do not always get adequate clinical attention. Pharmacotherapies for treating female sexual dysfunctions are available but suffer from drawbacks such as poor compliance, low efficacy, and side effects. Many patients and yoga protagonists claim that it is useful in improving sexual functions and treating sexual disorders. To establish the effect yoga can have on female sexual functions. We recruited 40 females (age range 22-55 years, average age 34.7 +/- 8.49 years) who were enrolled in a yoga camp and were given a standardized questionnaire named Female Sexual Function Index (FSFI) before and after the 12 weeks session of yoga. FSFI scores. It was found that after the completion of yoga sessions; the sexual functions scores were significantly improved (P < 0.0001). The improvement occurred in all six domains of FSFI (i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain). The improvement was more in older women (age > 45 years) compared with younger women (age < 45 years). Yoga appears to be an effective method of improving all domains of sexual functions in women as studied by FSFI.
Article
Sex and intimacy presents special challenges for the ostomate. Since some colorectal surgery patients will require either temporary or permanent stomas, intimacy and sexuality is a common issue for ostomates. In addition to the stoma, nerve damage, radiotherapy, and chemotherapy are often used in conjunction with stoma creation for cancer patients, thereby adding physiological dysfunction to the personal psychological impact of the stoma, leading to sexual dysfunction. The purpose of this paper is to describe the prevalence, etiology, and the most common types of sexual dysfunction in men and women after colorectal surgery and particularly those patients with stomas. In addition, treatment strategies for sexual dysfunction will also be described.
Article
Introduction: Women with familial cancer syndromes such as hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2) and Lynch syndrome are at a significantly increased risk of developing ovarian cancer and are advised to undergo prophylactic removal of their ovaries and fallopian tubes at age 35 to 40 years, after childbearing is complete. Methods: A comprehensive literature search of studies on risk-reducing salpingo-oophorectomy (RRSO), sexuality, and associated issues was conducted in MEDLINE databases. Results: Risk-reducing salpingo-oophorectomy can significantly impact on a woman's psychological and sexual well-being, with women wishing they had received more information about this prior to undergoing surgery. The most commonly reported sexual symptoms experienced are vaginal dryness and reduced libido. Women who are premenopausal at the time of surgery may experience a greater decline in sexual function, with menopausal hormone therapy improving but not alleviating sexual symptoms. Pharmacological treatments including testosterone patches and flibanserin are available but have limited safety data in this group. Conclusions: Despite the high rates of sexual difficulties after RRSO, patient satisfaction with the decision to undergo surgery remains high. Preoperative counseling with women who are considering RRSO should include discussion of its potential sexual effects and the limitations of menopausal hormone therapy in managing symptoms of surgical menopause.
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Background: Female Sexual dysfunction is a common neglected symptom of postmenopausal women in rural India. Prevalence of sexual dysfunction increases with age and sexual response is dynamic process influenced by socio-cultural, physiological, psychological and socio-economical factors. The objective of the study was to analyse the prevalence of female sexual dysfunctions in postmenopausal women from rural area and to analyze prevalence of sexual activity among them. Methods: A cross-sectional study was conducted from June 2015 to January 2016 in Obstetrics and Gynecology outpatient department of Indian Institute of Medical Science and Research, Badnapur, Jalna, Maharashtra which is a tertiary care centre. All postmenopausal women who have attained menopause naturally were questioned about sexual symptoms with the help of pre-tested questionnaires and then analyzed with appropriate tests. Results: Mean age of menopause was 47.59+/-3.98 yrs and 51.9% were sexually active. Mean age among sexual active and sexual inactive women was 54.42+/-5.23 and 62.13+/-6.39 respectively. Prevalence of dyspareunia, vaginal dryness and decreased libido were 10.7%, 10.7% and 55.36% respectively in sexually active postmenopausal women. Sexual activity decreased from 54.4% to 5.6% as the duration of menopause increased from 5 years or less to 11 or more years. Sexual dysfunction increased as the duration of menopause increased. Conclusions: Sexual dysfunction is common in postmenopausal women and increases with increasing duration of menopause. Awareness of health care facility among rural menopausal women should be increased to improve their quality of life. [Int J Reprod Contracept Obstet Gynecol 2016; 5(12.000): 4385-4389]
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Female sexual interest/arousal disorder (FSIAD), formerly known as hypoactive sexual desire disorder (HSDD), is characterized by reduced sexual interest, receptivity, pleasure, response, and sensation leading to personal distress and not related to a psychological disorder, medication, or medical condition. Low desire can be linked to situational circumstances, such as dysfunctional interpersonal relationships, or may have a physiologic cause related to chronic disease, certain medications, or hormonal factors. There is abundant research demonstrating that testosterone increases sexual desire and well-being in postmenopausal women with HSDD. Based upon this evidence, the transdermal testosterone patch is approved for treatment of women with HSDD in Europe and Australia. However, in the United States, the FDA has yet to approve a testosterone product for treating HSDD in women. There are many androgen and testosterone products under investigation, compounded preparations, and FDA-approved medications for men, which are commonly prescribed off label for women. This chapter will discuss medical management of HSDD, focusing on testosterone therapies in development.
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Sexual dysfunction in women is defined as disorders of sexual desire, arousal, orgasm, and/or sexual pain, which result in significant personal distress and may have a negative effect on a woman’s health and an impact on the quality of life. A comprehensive understanding of the anatomical, neurobiological, and psychological mechanisms behind women’s sexual function and dysfunction is of paramount importance. We sought to review the most frequent clinical pathophysiological mechanisms of women’s desire, arousal, and orgasmic dysfunctions. Likewise, we tried to consider the different disorders from the point of view of the daily clinical practice, trying to give an updated vision of lines of therapy currently being studied or of clear application, especially considering the disorders of sexual desire and arousal.
Article
The sexual response in women is considered to be multidimensional, involving hormonal, physiological, relational, emotional, and psychological parameters. It is also suggested that reduced level of testosterone in postmenopausal women is associated with loss of libido, decreased sexual activity, diminished feeling of physical well-being and fatigue. The transdermal testosterone patch is an effective treatment for hypoactive sexual disorder in surgically postmenopausal women. Testosterone is generally well tolerated. However, prospectively collected long-term studies are needed to estimate the risk of breast cancer and cardiovascular diseases.
Article
OVERVIEW This chapter examines the topic of sexuality in older adults: sexual behaviours and attitudes about ageing; types of sexual dysfunction and their prevalence; physiology and pathophysiology of the male and female sexual response; medical conditions affecting sexuality; endocrinological, psychiatric and psychosocial factors; female and male sexual dysfunctions and disorders; assessment and treatment considerations. Introduction In this new millennium, the topic of sexuality in older adults has finally come of age. Whereas conversations about the sexual behaviours of mature men and women were once whispered and private, it is now acceptable openly to discuss these matters in magazines and newspapers, on television, and even at dinner parties. The psychological and physiological impact of ageing on sexuality is particularly timely for a variety of reasons. The first reason has been labelled the ‘Viagratization of America’, a phenomenon that has expanded worldwide (Kingsberg, 2002). The development of phosphodiesterase type-5 (PDE-5) inhibitors, beginning with Viagra (sildenafil) in 1998, sparked a renewed interest in exploring the sexual activities of older people. Once men had a non-invasive method for treating the inevitable sexual effects of ageing, the topic took the media world by storm. Previously a matter of patient reticence, older men began to present to their physicians anticipating the provision of particular therapies to enhance sexual performance. Viagra became a household name. Even a former American presidential candidate, Bob Dole, became a spokesperson for Viagra and discussed his erectile dysfunction (ED) in television ads.
Article
Sexual disorders include both sexual dysfunctions and paraphilias. Sexual dysfunctions are sexual disorders characterized by problems that occur during the phases of the sexual response cycle. Paraphilias "are characterized by recurrent, intense sexual urges, fantasies, or behaviors that involve unusual objects, activities, or situations." (DSM-IV-TR; American Psychiatric Association [APA], 2000, p. 535).
Article
IntroductionSexual dysfunction is an under-recognized problem in men and women with obstructive sleep apnea (OSA). Epidemiologic findings were inconclusive regarding the risk for sexual dysfunction associated with OSA.AimThe aim of this study was to examine the association between OSA and sexual dysfunction.Methods The PubMed, Cochrane Library, and Embase databases were searched for observational studies on the OSA and the risk of sexual dysfunction. The methodologic quality of the case–control and cohort studies was assessed with Newcastle–Ottawa Scale (NOS). The cross-sectional study quality methodology checklist was used for cross-sectional study. Data were pooled for the random-effects model. Sensitivity analyses were conducted to assess potential bias.Main Outcome MeasureThe association between OSA and sexual dysfunction was summarized using relative risk (RR) with a 95% confidence interval (CI).ResultsThis meta-analysis included 1,275 participants from nine studies. Five studies reported the incidence of erectile dysfunction (ED); the remaining four studies reported the incidence of female sexual dysfunction (FSD). Pooled results demonstrated that OSA was associated with increased risk of ED (pooled RR = 1.82, 95% CI: 1.12–2.97) as well as FSD (pooled RR = 2.00, 95% CI: 1.29–3.08). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed.Conclusions Evidence from the observational studies suggested that OSA individuals might have an increased incidence of sexual dysfunction despite significant heterogeneity. More researches are warranted to clarify the relationship between OSA and the increased risk of sexual dysfunction. Liu L, Kang R, Zhao S, Zhang T, Zhu W, Li E, Li F, Wan S, and Zhao Z. Sexual dysfunction in patients with obstructive sleep apnea: A systematic review and meta-analysis. J Sex Med **;**:**–**.
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An up-to-date review of the impact of a permanent sacral neuromodulation (SNM) implant (Medtronic, Minneapolis, Minnesota, USA) on female sexual function (FSF). Clinical studies published from January 2001 to February 2014 evaluating the impact and/or safety of permanent SNM on FSF were reviewed. Nine studies were selected that investigated the impact on sexual response when the aim of the SNM was to resolve urinary symptoms mainly due to overactive bladder (seven studies) or faecal incontinence. Most women included were of menopausal age. Three studies included sexually inactive women. Post-SNM follow-up varied from 3 to 36 months. Meta-analysis of efficacy results was not possible primarily due to the heterogeneity of the sexual and pelvic dysfunctions. The most specific questionnaire assessing FSF was the Female Sexual Function Index (FSFI) used in six studies. During follow-up all women showed statistically significant improvement (p < 0.05) in at least one FSFI domain compared to baseline. In one study statistically significant improvement (p < 0.05) in the FSFI pain domain was exclusively detected in women with neurological disease. Two studies, however, using the questionnaire to screen for sexual dysfunction did not find any statistically significant differences after SNM. The most severe problems associated with FSF concern loss of libido and reduction in vaginal lubrication which were resolved in one woman following removal of the SNM implant. Actual data are still insufficient to definitely assert the positive effect of SNM on FSF.
Article
Despite some increased visibility in recent years, the asexual community and asexuality generally remain largely unknown. Aiming to demystify asexuality, this paper discusses the context of anti-asexual animosity in which the (largely American) asexual community is situated. Specifically, the asexual community constructed itself in response to hostility, including explicit anti-asexual discrimination, homophobia against asexual people perceived to be lesbian or gay, and the negative impact of (implicit) pathologising low sexual desire. This theoretical paper outlines some of the unique challenges asexual people face negotiating identities and relationships; the collective sense-making strategies they use (generating language and discourse) to do so; and why these things are central to understanding asexual people's experiences. This is accomplished through a purposeful review of literature and a case study of the Asexual Visibility and Education Network as an asexual community space. Understanding the challenges asexual people face and the resources they invoke to overcome them helps applied psychologists develop the cultural competence they need to work effectively with the asexual people they will encounter. Copyright © 2014 John Wiley & Sons, Ltd.
Article
Female sexual dysfunction is a common problem, yet it is often under-treated. Sexual function is an integral part of the human experience and sexual dysfunction can negatively impact quality of life, yet many patients suffer in silence with their problems. This article provides a common case scenario, along with information on prevalence of female sexual dysfunction, definitions and classifications of female sexual dysfunction as well as some of the treatment options available.
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Objectif Cet article a pour ambition de proposer aux cliniciens un modèle permettant le repérage des éléments dysfonctionnels responsables de l’apparition ou du maintien du Désir Sexuel Hypoactif. Méthodologie En nous appuyant sur une large recension des écrits cliniques et empiriques, nous suggérons une vision globale dont les fondements théoriques viennent de la sexofonctionnelle. Résultats Ce modèle souligne le caractère multifactoriel du Désir Sexuel Hypoactif et nous conduit vers une structuration didactique en cinq axes. Discussion De cette manière, les facteurs (1) cognitifs, (2) physiologiques, (3) comportementaux, (4) émotionnels et (5) environnementaux sont discutés. Conclusions Cette étiologie en cinq axes facilitera l’évaluation de l’ensemble des éléments responsables du Désir Sexuel Hypoactif et permettra aux cliniciens une adaptation de leur traitement en fonction d’une anamnèse attentive au caractère multifactoriel du Désir Sexuel Hypoactif.
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Object The purpose of this article is to propose a model to clinicians designed to highlight the dysfunctional elements responsible for the appearance and continuation of Hypoactive Sexual Desire Disorder. Methodology Supported by a broad analysis of clinical and empirical accounts, we suggest a global vision whose theoretical foundations come from “sexofonctionnelle”. Results This model underlines the multi-factor aspect of Hypoactive Sexual Desire Disorder and leads us to a didactical structuration comprising five axes. Discussion Thereby, the cognitive, physiological, behavioural, emotional and environmental factors are discussed. Conclusion This etiology with its five axes will facilitate the assessment of all the elements responsible for Hypoactive Sexual Desire Disorder and will enable clinicians to adapt their treatment by being aware of the multi-factor nature of Hypoactive Sexual Desire Disorder when taking a medical history.
Article
Cancer today is more of a chronic than a fatal disease: the improving survival rates increase the likelihood of long survival after the diagnosis. Unfortunately, cancer treatment is the most frequent cause of premature iatrogenic menopause and psychosexual dysfunction. Therefore, an increasing number of cancer survivors have to cope with both the consequences of cancer treatment per se, the complex physical and psychological changes secondary to a premature iatrogenic menopause, and the burden of sexual dysfunctions, more difficult to accept in the youngest patients. Female sexual identity may be variably affected by a cancer diagnosis and treatment depending on the age at diagnosis (and the age at the time of any recurrences). Age is the first biological factor that may modify the outcome of cancer diagnosis and treatment, when sexuality is considered as an independent variable in the quality of life (QOL) evaluation. The impact of cancer is increasingly worse in younger patients, especially if radical surgery, adjuvant systemic chemotherapy, and/or local radiotherapy further reduce the biological chances of a fulfilling sexual and procreative life.
Article
A large number of men over 60 years of age have low bioavailable of free testosterone levels and symptoms of testosterone deficiency. These symptoms include loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strength, increased fat mass, frailty, osteopenia and osteoporosis. Clinical trials indicate that testosterone therapy can improve many of these findings. In the past, androgen use in clinical practice was impeded or limited, since efficient oral or parental administration of testosterone was impossible. The introduction of modern transdermal testosterone-delivery systems has changed this situation fundamentally. Its clinical efficacy in reversing symptoms of hypogonadism has been demonstrated. The main advantage of the transdermal testosterone gel is easy handling or applicability, lack of visibility, flexibility in dosing and the low rate of minimal skin irritation resulting in good compliance. Current experiences suggest that testosterone gel may be the most physiological and well-tolerated transdermal testosterone-delivery system yet. Application of the gel is simple, practicable for the patient and replaces painful intramuscular injections. Owing to the short action of testosterone gel, application can be ceased in case of the appearance of side effects, such as an excessive increase in hematocrit, prostate-specific antigen or an abnormal digital rectal examination.
Article
Hypoactive sexual desire disorder (HSDD), a subset of female sexual dysfunction, causes personal distress for surgically and naturally postmenopausal and premenopausal women. HSDD has a multi-factorial etiology, including psychosocial factors such as relationship issues and medical factors such as medications, chronic illnesses, and hormonal effects. Although no androgen therapies for female sexual dysfunction are currently approved for use in Canada, clinical trials support the efficacy and short-term safety of testosterone therapy for HSDD. We review the scientific evidence for the safety of testosterone therapy for HSDD.
Article
Recent data report an important role of testosterone (T) in modulating female sexual responses, but little is known about the expression and distribution of androgen receptor (AR) in the human vagina. Therefore, the aims of our study were to evaluate the expression of AR in the human vagina in premenopausal (PrM) and menopausal (M) women and in T-treated women. Vaginal biopsies were obtained from PrM and postmenopausal women and from women with gender identity disorder (female to male (FtM)) receiving exogenous T. AR gene and protein expression levels in vaginal tissues were determined by real-time PCR and western blot analysis, respectively, whereas the localization of AR in vaginal mucosa and stroma was performed by immunohistochemistry. ARs were detected by immunostaining both in the mucosa and stroma. In vaginal mucosa, AR density score decreases with age but does not change with T administration. In stromal tissue, AR density score does not change with age but significantly increases with T administration (P<0.01). AR protein expression was significantly increased in FtM subjects (P<0.001). The expression of AR messenger RNA (mRNA) evaluated by Real-time PCR showed a significantly higher mRNA expression in FtM versus M patients (P<0.01) and in PrM versus M subjects (P<0.05). In conclusion, we found AR protein and mRNA expression both in the epithelium and stroma of the human vagina in all groups of women. A negative correlation exists between age and AR expression in the vaginal mucosa. T administration increases AR expression in both the mucosa and stroma.International Journal of Impotence Research advance online publication, 28 June 2012; doi:10.1038/ijir.2012.25.
Article
Introduction: Testosterone replacement therapy in naturally and surgically menopausal women is a complex and currently highly debated topic. Opposing guidelines for the use of testosterone exist, which create a therapeutic dilemma for clinicians confronted by severely distressed women who experience a decrease in sexual desire after surgical or natural menopause. Aim: In this review, we will address the current knowledge on androgen physiology, conditions associated with a low androgen state, and risks and benefits of androgen therapy. Methods: An English-language Medline review was performed. Main outcome measure: Review of available literature. Results: A review of normal androgen physiology in women is summarized and a brief review of prior use of androgens over the last six decades is included. The data on the use of androgen replacement in pre- and postmenopausal women is evaluated, especially its relationship to sexual functioning. Special concerns about the effect of androgens on cardiovascular disease, breast, and endometrial tissue are discussed. The balance of evidence seems to show that androgens have more of a positive effect than a negative effect in women if used properly. Conclusions: Testosterone replacement therapy for surgically and naturally menopausal women with low sexual desire can be accomplished physiologically and effectively after ruling out other medical conditions leading to low sexual desire and after proper information of the patient that testosterone therapy is not an FDA-approved medication in the United States. The majority of available data suggests that testosterone replacement in women can be used safely without increased risk of endometrial or breast cancer.
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The waiting room of a busy oncology practitioner’s office will include women patients who may also have sexual health concerns [1–7]. In many cases, the sexual health problems of these oncologic patients will be highly associated with their female oncologic health care problems and/or the treatments for their oncologic condition [8–12]. In the vast majority of cases, however, while great attention is provided to the oncologic concern, there is only limited attention given to their sexual health problems. KeywordsArousal-Engorgement-Lubrication-Neurotransmitters-Androgens-Hormones
Article
Although sexuality remains an important component of emotional and physical intimacy that most men and women desire to experience throughout their lives, sexual dysfunction in women is a problem that is not well studied. The prevalence of sexual dysfunction among all women is estimated to be between 25% and 63%; the prevalence in postmenopausal women is even higher, with rates between 68% and 86.5%. Increasing recognition of this common problem and future research in this field may alter perceptions about sexuality, dismiss taboo and incorrect thoughts on sexual dysfunction, and spark better management for patients, allowing them to live more enjoyable lives.
Article
Transdermal hormone therapy is replacing oral estrogens and androgens as safe enhancements of life quality for postmenopausal women. Estradiol and testosterone are dosed into the microvascular circulation directly through skin so there is no first-pass hepatic transformation or deactivation of the dosed estradiol or testosterone. This review critically examines recent clinical trials describing experience with transdermal estradiol and testosterone in postmenopausal women. Transdermal estradiol is effective in the treatment of vasomotor symptoms (VMS) and can provide its benefits at higher levels of safety than have been heretofore possible with oral estrogens. Transdermal testosterone is effective in the treatment of hypoactive sexual desire disorder (HSDD) documented in multiple, well-powered randomized clinical trials with demonstrated high levels of safety. The reader will learn that transdermal estradiol and testosterone, in properly selected postmenopausal women, significantly and safely enhance life quality, are likely to become increasingly popular, and will probably replace oral hormone therapy. Transdermal delivery of native estradiol for VMS and testosterone for HSDD has significant advantages in safety and efficacy over traditional oral preparations which are now available for clinical use.
Article
Testosterone, like other steroid hormones, crosses the blood–brain barrier, and the androgen receptor is present in most parts of the human brain. Therefore, testosterone has many effects on the psyche, mainly in men but also in women. Most often discussed is its influence on sexuality, especially on desire and sexual fantasies, spontaneous nighttime erections, sexual activity, and the number of orgasms and ejaculations. Mood and energy are also testosterone related. Testosterone deficiency in male patients can lead to depressive disorders. In the past, elevated testosterone levels were seen as responsible for strongly aggressive behaviour. Some cognitive functions (spatial and mathematical sense, verbal skills) are, at least to a certain point, testosterone related. Due to the extremely complex functioning of the human brain, a scientifically exact statement regarding the true relationship between testosterone and human behaviour is not possible. On the one hand, the cause is definitively multifactorial, but on the other, testosterone is metabolised in the brain, and the metabolites act by themselves. Furthermore, a bidirectional relationship exists between hormones and human behaviour: Human behaviour is influenced by hormones, and human behaviour also has a direct influence on the levels of many hormones in the human body. Finally, much data in this field are derived from animal studies; studies on humans cannot be conducted because of ethical reasons or scientific and technical problems.
Article
There are no testosterone products approved for women by the Food and Drug Administration (FDA). Testosterone is often prescribed "off-label" to women for the treatment of hypoactive sexual desire disorder (HSDD).
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The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. Seventy-five women, 31 to 56 years old, who had undergone oophorectomy and hysterectomy received conjugated equine estrogens (at least 0.625 mg per day orally) and, in random order, placebo, 150 microg of testosterone, and 300 microg of testosterone per day transdermally for 12 weeks each. Outcome measures included scores on the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and a sexual-function diary completed over the telephone. The mean (+/-SD) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter (4.2+/-2.8 pmol per liter) during placebo treatment to 3.9+/-2.4 pg per milliliter (13.5+/-8.3 pmol per liter) and 5.9+/-4.8 pg per milliliter (20.5+/-16.6 pmol per liter) during treatment with 150 and 300 microg of testosterone per day, respectively (normal range, 1.3 to 6.8 pg per milliliter [4.5 to 23.6 pmol per liter]). Despite an appreciable placebo response, the higher testosterone dose resulted in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women (P=0.03 for both comparisons with placebo). At the higher dose the percentages of women who had sexual fantasies, masturbated, or engaged in sexual intercourse at least once a week increased two to three times from base line. The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose (P=0.04, P=0.03, and P=0.04, respectively, for the comparison with placebo), but the scores on the telephone-based diary did not increase significantly. In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being.
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Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population. To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region. A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS. Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1-4) was the response to the question: "Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?" Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS. The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1-4 (56% v 35%, respectively; p<0.0001) and weeks 1-12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo). Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.
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There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients. This placebo-controlled study of sertraline was designed to confirm the results of non-placebo-controlled trials. The subjects were outpatients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher. The patients were randomly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline. The primary outcome variables were the Hamilton scale and Clinical Global Impression (CGI) scales for severity and improvement. A total of 371 patients assigned to sertraline and 376 assigned to placebo took at least one dose. At endpoint, the patients receiving sertraline evidenced significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales. The mean changes from baseline to endpoint in Hamilton score were -7.4 points (SD=6.3) for sertraline and -6.6 points (SD=6.4) for placebo. The rate of CGI-defined response at endpoint was significantly higher for sertraline (45%) than for placebo (35%), and the time to sustained response was significantly shorter for sertraline (median, 57 versus 61 days). There were few discontinuations due to treatment-related adverse events, 8% for sertraline and 2% for placebo. Sertraline was effective and well tolerated by older adults with major depression, although the drug-placebo difference was not large in this 8-week trial.
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Hypoactive sexual desire disorder (HSDD) is one of the most common sexual problems reported by women, but few studies have been conducted to evaluate treatments for this condition. The objective of this study was to evaluate the efficacy and safety of a testosterone patch in surgically menopausal women with HSDD. The design was a randomized, double-blind, parallel-group, placebo-controlled, 24-wk study (the Intimate SM 1 study). The study was performed at private or institutional practices. The subjects studied were women, aged 26-70 yr, with HSDD after bilateral salpingo-oophorectomy who were receiving concomitant estrogen therapy. Placebo (n = 279) or testosterone 300 microg/d (n = 283) was administered. There were 19 patients who withdrew due to adverse events in the placebo group and 24 in the 300 mug/d testosterone group. Testosterone (300 microg/d) or placebo patches were applied twice weekly. MAIN OUTCOME MEASURE(s): The primary end point was the change in the frequency of total satisfying sexual activity at 24 wk. Secondary end points included other sexual functioning end points and safety assessments. At 24 wk, there was an increase from baseline in the frequency of total satisfying sexual activity of 2.10 episodes/4 wk in the testosterone group, which was significantly greater than the change of 0.98 episodes/4 wk in the placebo group (P = 0.0003). The testosterone group also experienced statistically significant improvements in sexual desire and a decrease in distress. The overall safety profile was similar in both treatment groups. In the Intimate SM 1 study, the testosterone patch improved sexual function and decreased distress in surgically menopausal women with HSDD and was well tolerated in this trial.
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Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women. A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted in women (aged 24-70 years) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy. Women were randomized to receive placebo (n = 119) or testosterone patches in dosages of 150 microg/d (n = 107), 300 microg/d (n = 110), or 450 microg/d (n = 111) twice weekly for 24 weeks. Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures. Of the 447 women randomized, 318 (71%) completed the trial. Compared with placebo, women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P = .05) and in frequency of satisfying sexual activity (79% vs 43%; P = .049). The 150-microg/d group showed no evidence of a treatment effect. The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups. Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P = .06 and .06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed. The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause.
Article
Background: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. Methods: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. Results: Lamotrigine 200mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as Week 3. Lamotrigine 50mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51 percent, 41 percent, and 26 percent for lamotrigine 200mg/day, lamotrigine SOmg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. Conclusion: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.
Article
Objective: This position statement aimed to update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2010 regarding recommendations for hormone therapy (HT) for postmenopausal women. This updated position statement further distinguishes the emerging differences in the therapeutic benefit-risk ratio between estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) at various ages and time intervals since menopause onset. Methods: An Advisory Panel of expert clinicians and researchers in the field of women's health was enlisted to review the 2010 NAMS position statement, evaluate new evidence, and reach consensus on recommendations. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. Results: Current evidence supports the use of HT for perimenopausal and postmenopausal women when the balance of potential benefits and risks is favorable for the individual woman. This position statement reviews the effects of ET and EPT on many aspects of women's health and recognizes the greater safety profile associated with ET. Conclusions: Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms and to prevent osteoporosis in women at high risk of fracture. The more favorable benefit-risk ratio for ET allows more flexibility in extending the duration of use compared with EPT, where the earlier appearance of increased breast cancer risk precludes a recommendation for use beyond 3 to 5 years.
Article
Introduction. Although several conceptual frameworks for female sexual dysfunction (FSD) have been advanced, there still is considerable disagreement over what constitutes a normal vs. abnormal response. Sexual dysfunction is a disturbance in sexual functioning involving one or multiple phases of the sexual response cycle or pain associated with sexual activity, while a sexual disorder includes both dysfunction and marked distress. Aim. Review the literature regarding the epidemiology and neurobiology of FSD. Methods. Review of the literature. Results. While a wide range of epidemiologic studies has been published, it is still difficult to determine the scope of FSD and sexual disorders in the general population. It is becoming clear that good sexual health is associated with good physical and mental health as well as compatible relationships with one's sexual partner. Central nervous system (CNS) control of the sexual response is a relatively new area of scientific exploration. Conclusions. We are improving our understanding of the contributions of the CNS neuroendocrine and neurotransmitter systems that modulate sexual behavior. Clayton AH. Epidemiology and neurobiology of female sexual dysfunction. J Sex Med 2007;4(suppl 4):260–268.
Article
Introduction: Approximately one out of four sexually active women in the United States uses some form of hormonal contraceptive method because they provide the most effective reversible method of birth control available. However, little attention has been paid to possible adverse effects of combined oral contraceptives (COCs) on sexual functioning. Aim: The aim of this study was to examine the potential effects of COCs on women with hypoactive sexual desire disorder (HSDD). It was hypothesized that female patients with generalized, acquired HSDD on COCs have lower androgen levels than those not on COCs. Methods: The patients were healthy premenopausal women with HSDD, aged 22-50 years. Subjects had a history of adequate sexual desire, interest, and functioning. Participants were required to be in a stable, monogamous, heterosexual relationship and were screened for any medication or medical or psychiatric disorders that impact desire. The patients met operational criteria for global, acquired HSDD. The 106 patients were divided into two groups: those on COCs (N = 43) and those not on COCs (N = 63). A two-tailed t-test comparison was made between the two groups comparing free and total testosterone and sex hormone-binding globulin (SHBG). Main outcome measures: The main outcome measures are the differences between the two groups comparing free testosterone, total testosterone, and SHBG. Results: These patients with HSDD on COCs had significantly lower free and total testosterone levels compared with those who were not on COCs. The SHBG was significantly higher in the group on COCs compared with those who were not on COCs. Conclusion: The result of this study suggests that COCs in premenopausal women with HSDD are associated with lower androgen levels than those not on COCs. Further research is required to determine if low androgen levels secondary to COCs impact female sexual desire.
Article
Introduction: Postmenopausal women with hypoactive sexual desire disorder (HSDD) experienced statistically significant improvements in the frequency of satisfying sexual activity, sexual desire, and distress with testosterone treatment in phase III trials, but it was not known whether the magnitude of these effects was clinically meaningful. The clinical relevance study was designed to answer this question. Aim: To evaluate the clinical relevance of the treatment benefits. Methods: This study involved a representative sample of 132 surgically postmenopausal women with HSDD who were enrolled in two randomized, placebo-controlled trials (N = 1094) assessing the efficacy and safety of transdermal testosterone treatment (300 mcg/day) for 6 months. At the end of the studies, prior to unblinding, a sample of women (12%) was interviewed concerning their experiences with the treatment. Main outcome measures: Women were asked "Overall, would you say that you experienced a meaningful benefit from the study patches?" Changes in the efficacy end points in the double-blind studies were compared for the women who did and did not experience an overall meaningful benefit. Results: Overall, 33 of 64 women (52%) who received testosterone reported experiencing a meaningful treatment benefit, compared with 21 of 68 women (31%) who received placebo (P = 0.025). Among the women who identified themselves as experiencing a meaningful benefit, the mean (SE) change from baseline in 4-week frequency of satisfying sexual activity was 4.4 (0.76), in desire score was 21.0 (2.78), moving from "seldom" to "sometimes" feeling sexual desire, and in distress score was -36.5 (3.96), moving from "often" to "seldom" being distressed. Among the women who identified themselves as not experiencing a meaningful benefit, the mean (SE) change from baseline in 4-week frequency of satisfying sexual activity was 0.5 (0.31), in desire score was 2.9 (1.42), and in distress score was -8.8 (2.23). Conclusions: Surgically menopausal women with HSDD in these studies received clinically meaningful benefits, including improvements in satisfying sexual activity, sexual desire, and personal distress.
Article
The complex condition of the menopause is experienced by all women going through the physical and emotional changes associated with ovarian sexual hormones loss. It may impact directly on their physical and mental health. The complexity of this condition makes it necessary to accumulate large bodies of data to define the patterns and trends in its evaluable manifestations. To this end, large amounts of data were collected on women from France, Germany, Italy, and the United Kingdom, via the Women's International Survey on Health and Sexuality. The key measures within the survey were the Profile of Female of Sexual Function (PFSF and the Personal Distress Scale (PDS. The survey yielded 2,467 responders aged between 20 and 70, capturing women with surgical and natural menopausal status and those with premenopausal status. In the four EU countries studied, sexual activity decreases by age. An increase in female sexual dysfunction (FSD), particularly loss of sexual desire, is directly correlated with increasing age. However, the distress associated with loss of sexual desire is inversely correlated with age. Cultural and context-dependent factors modulate the percentage of any FSD in the different European countries. This is exemplified in the significant intercountry variation observed in the percentage of low desire in women aged 20-49, with normal ovarian function. However, when women undergo surgical menopause, with concomitant loss of their sexual hormones, the culture-related differences are blunted. The findings of this survey have implications for the understanding of hypoactive sexual desire disorder (HSDD), not only the way it should be assessed in clinical practice, but also the most appropriate means for its treatment. Testosterone deficiency is a significant cause of HSDD, and new therapies have been investigated which offer considerable potential to address this hormonal etiology.
Article
Five aspects of sexual behavior were monitored daily in three groups of women who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy approximately 4 years ago for benign disease. One group had been receiving an estrogen-androgen preparation intramuscularly once a month since their surgery (E-A). The second group had been receiving estrogen alone (E) and the third group of women had remained untreated. Plasma estradiol and testosterone were measured at an established baseline and again on days 2, 4, 8, 15, 21, and 28 postinjection. Women who received both sex steroids reported higher rates of sexual desire (p less than 0.01), sexual arousal (p less than 0.01), and numbers of fantasies (p less than 0.01) than those who were either given E or who were untreated. Moreover, changes in these behaviors covaried with plasma testosterone but not with plasma estradiol levels during the treatment month as the drug was being metabolized. Rates of coitus and orgasm were also higher in the E-A group during the first two postinjection weeks (p less than 0.01) coincident with their higher testosterone levels. These findings imply that androgen may be critical for the maintenance of optimal levels of sexual functioning in postmenopausal women.
Article
Twenty premenopausal, 14 postmenopausal, and 14 postmenopausal women receiving replacement estrogen therapy were studied to determine whether differences in hormone status were associated with differences in physiological and subjective sexual responses. All subjects viewed a neutral, an erotic, and a second neutral videotape while photoplethysmographic vaginal pulse amplitude was continuously recorded. Self-report ratings of sexual arousal and affective response were collected. Serum levels of testosterone, estradiol, estrone, and luteinizing hormone were obtained. The three groups did not differ in either average or maximum vaginal pulse amplitude to the videotapes nor in latency of sexual response. The postmenopausal women not taking replacement estrogen reported significantly less vaginal lubrication in response to the erotic videotape than the higher estrogen premenopausal and replacement hormone groups. Estradiol level was significantly correlated with ratings of vaginal lubrication in response to the erotic videotape but not with vaginal pulse amplitude. Results thus suggest that estrogen is important in maintaining vaginal lubrication and the perception of sexual arousal but not in determining vaginal vasocongestion.
Article
Various parameters of sexual functioning were assessed in a prospective, crossover investigation of 53 surgically menopausal women. Patients randomly received either an estrogen-androgen combined preparation, an estrogen-alone drug, an androgen-alone drug, or a placebo. Also included were a group of women who had undergone hysterectomy and whose ovaries had been left intact. Two treatment phases, each of 3 months' duration, were separated by an intervening placebo month. Additionally, plasma levels of total estrogens and testosterone were assayed four times during the study concurrent with monitoring of sexual behaviors. It was clear that exogenous androgen enhanced the intensity of sexual desire and arousal and the frequency of sexual fantasies in hysterectomized and oophorectomized women. However, there was no evidence that testosterone affected physiologic response or interpersonal aspects of sexual behavior. These findings suggest that the major impact of androgen in women is on sexual motivation and not on sexual activity per se.
Article
Eight women who had been maintained on a combined estrogen-androgen drug since hysterectomy and bilateral oophorectomy 2 yr previously were investigated for changes in sexual behavior during the course of 1 treatment cycle. Following intramuscular injection of both sex steroids, plasma estradiol levels were within the normal range of young, cycling women but plasma testosterone exceeded the upper limit of normal female values. Sexual motivational behaviors (desire, fantasies and arousal) covaried with plasma steroid levels. Rates of coitus and orgasm, however, were unrelated to the changing levels of circulating hormones. A differential effect of the sex steroids on various aspects of sexual functioning was thus confirmed.
Article
From an initial group of 39, 16 cycling peri-menopausal women completed a longitudinal study in which they recorded menstrual and sexual behavior daily and were interviewed at roughly 4-mth intervals until 1 yr or more without cycling. At each interview women gave 20-ml blood samples, completed sexuality questionnaires, and rated themselves for menopausal symptoms. As predicted, the difference in weekly rate of sexual intercourse before and after the cycle showed a significant decline (P less than 0.05). For each subject, mean weekly rates of sexual intercourse for 13-wk periods over the entire transition period were plotted and the slope of the line was calculated. Overall, the mean slope was negative, as predicted, and was significantly different from zero (P less than 0.05). The questionnaire data showed that compared with their pre-menopause data, the women had fewer sexual thoughts or fantasies (P less than 0.01), suffered more from lack of vaginal lubrication during sex (P less than 0.01), and were less satisfied with their partners as lovers (P less than 0.05) after menopause. While estradiol (E) and testosterone (T) levels showed significant declines (P less than 0.02), testosterone showed the most consistent association with coital frequency. The findings generally supported our initial hypothesis of a decline in sexual interest and coital frequency after menopause.
Article
This report describes a model of steroid transport in human plasma. The binding affinities of 21 endogenous steroids for both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were determined under equilibrium conditions using a solid phase method at physiological pH and temperature. A computer program was used to solve the complex equilibrium interactions between these steroids and TeBG, CBG, and albumin. In this manner, we calculated the plasma distribution of each steroid into TeBG-bound, CBG-bound, albumin-bound, and unbound fractions in normal men, normal women during both the follicular and luteal phases of the ovarian cycle, and women during the third trimester of a normal pregnancy.
Article
To investigate the role of androgens in increasing bone density and improving low libido in postmenopausal women, we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal volunteers were randomised to treatment with either estradiol implants 50 mg alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered 3-monthly for 2 years. Cyclical oral progestins were taken by those women with an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total body, lumbar vertebrae (L1-L4) and hip area increased significantly in both treatment groups. BMD increased more rapidly in the testosterone treated group at all sites. A substantially greater increase in BMD occurred in the E&T group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric (P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating scale) improved significantly in both groups. Addition of testosterone resulted in a significantly greater improvement compared to E for sexual activity (P < 0.03), satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both groups as did total body fat. Total body fat-free mass (DEXA, anthropometry, impedance) increased in the E&T group only. We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.
Article
In a study of the endocrinology of the perimenopausal years, levels of serum FSH, estradiol (E2), immunoreactive inhibin (INH), testosterone, and sex hormone-binding globulin were measured in a population-based sample of 380 women (mean age, 49.4 yr; range, 45.6-56.9 yr). Subjects were divided into women who reported continuing regular menstrual cycles (27%; group I), a change in menstrual flow without a change in frequency (23%; group II), a change in frequency but no change in flow (9%; group III), changes in both frequency and flow (28%; group IV), and at least 3 months since their last menstrual period (13%; group V). After adjusting for age and body mass index, the geometric mean FSH increased across menstrual groups and, compared with group I, was 53% higher in group IV (P < 0.0005) and 253% higher in group V (P < 0.0001). Age- and body mass index-adjusted geometric means for E2 and INH in group V were 54% and 53% of those in group 1, respectively (P < 0.005, P < 0.0001). Women in group V who did not have a menstrual period in the next year had higher FSH and lower E2 and INH levels than those who subsequently went on to have at least one more menstrual period (P < 0.05). FSH was negatively correlated with E2 (r = -0.30) and INH (r = -0.39), whereas INH was positively correlated with E2 (r = 0.45). We conclude that an increase in serum FSH and decreases in E2 and INH are the major endocrine changes associated cross-sectionally with the menopausal transition.
Article
More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.
Article
This study examines the cross-sectional association of hysterectomy and oophorectomy status, chronological age, and years since menopause with plasma levels of total and bioavailable testosterone and estradiol, androstenedione, estrone, and sex hormone-binding globulin (SHBG) in community-dwelling postmenopausal women who were not using estrogen replacement therapy. Six hundred and eighty-four women, aged 50-89 yr, were surveyed for hysterectomy and oophorectomy status and had plasma obtained between 1984-1987. Of these, 438 (67%) had not undergone hysterectomy or oophorectomy (intact), 123 (18%) reported hysterectomy with bilateral oophorectomy, and 123 (18%) reported hysterectomy with conservation of 1 or both ovaries. After adjustment for age and body mass index, both total and bioavailable testosterone levels were reduced by more than 40% (P < 0.001) in hysterectomized women with bilateral oophorectomy compared to those in intact women, with intermediate levels observed in hysterectomized women with ovarian conservation. Androstenedione levels were about 10% lower in hysterectomized women with or without ovarian conservation compared to those in intact women (P = 0.039). Total estradiol levels tended to be lower (P = 0.095) in bilaterally oophorectomized women. Levels of bioavailable estradiol, estrone, and SHBG did not differ by hysterectomy and oophorectomy status. Among intact women, total, but not bioavailable, testosterone levels increased with age (P = 0.015), reaching premenopausal levels for the 70-79 decade with relatively stable levels thereafter. Among oophorectomized women, total and bioavailable testosterone levels did not vary with age and were 40-50% lower than those in intact women throughout the 50-89 yr age range. Androstenedione levels decreased 27% and SHBG levels increased 30% (P < 0.001) with age in intact, but not oophorectomized, women. Levels of other hormones did not vary with age. Stratification by years since menopause or surgery yielded similar results. These results demonstrate that the postmenopausal ovary remains a critical source of androgen throughout the lifespan of older women. The clinical consequences of lower testosterone levels years after oophorectomy are unknown. Reconsideration of prophylactic oophorectomy and clinical trials to evaluate the effects of androgen replacement after oophorectomy are needed.
Article
The aims of this study were to describe, in relation to date of final menses, the average androgen levels of women in the years before and after this date, and to determine the extent to which these average levels were dependent on age and body mass index (BMI) and the degree of tracking in residual androgen levels, or the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses. Serial levels of serum sex hormone-binding globulin (SHBG), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured annually in 172 women from the Melbourne Women's Midlife Health Project who experienced a natural menopause during 7 yr of follow-up. Fasting blood samples were drawn between days 4-8 if women were still menstruating or after 3 months of amenorrhea. The free androgen index (FAI) was calculated as the ratio ofT to SHBG x 100. Means of the log-transformed androgen levels were analyzed as a double logistic function of time relative to FMP as well as age and BMI, and correlations between repeated androgen levels were measured. Mean SHBG levels decreased by 43% from 4 yr before to 2 yr after the FMP. The time of most change was 2 yr before FMP [95% confidence interval (CI), 0.8-3.2]. SHBG levels were, on the average, 5% lower for each halving of estradiol (E2) levels and 4% lower for each kilogram per m2 of BMI (P < 0.0001). About one third of the decline in SHBG was explained by E2 and BMI. After adjusting for all variables, SHBG showed strong tracking. Mean T levels did not vary with time relative to FMP and were independent of age and BMI. Residual values of T showed weak tracking. The FAI increased by 80% from 4 yr before FMP to 2 yr after FMP, and changed maximally 2.2 yr before FMP (95% CI, 1.2-3.2). The FAI was not related to age or E2, but was, on the average, 4% higher for each kilogram per m2 of BMI (P < 0.0001). Residual values of FAI showed moderate tracking. Mean DHEAS levels were not related to the FMP, but were 1.5% lower for each year of age (P < 0.01) and 3.8% lower for each kilogram per m2 of BMI (P < 0.0001). Residual values of DHEAS showed strong tracking. It is concluded that SHBG and FAI levels change at the time of the menopause, at least partially due to the decline in E2. DHEAS decreases as a function of age, not time relative to FMP, and T remains unchanged during the menopausal years. SHBG and DHEAS show a high degree of stability within an individual over time.
Article
To develop a new scoring algorithm for the Brief Index of Sexual Functioning for Women (BISF-W) and to compare results from a normative population with those from a clinical sample of surgically menopausal women with impaired sexual function. The scoring algorithm provided an overall composite score and seven dimension scores: D1 (thoughts/desires), D2 (arousal), D3 (frequency of sexual activity), D4 (receptivity/initiation), D5 (pleasure/orgasm), D6 (relationship satisfaction), and D7 (problems affecting sexual function). The normative population consisted of 225 healthy women between the ages of 20 and 55 years; 187 had regular sexual partners and 38 did not. The clinical sample comprised 104 women in the same age range (with partners), who reported that their sex lives had become less active or less satisfying after surgery (bilateral oophorectomy and hysterectomy), despite standard estrogen replacement therapy. The BISF-W composite and dimension scores for healthy women with partners were significantly greater (p < 0.001) than for women without partners, except for D1, which was comparable in both groups. For healthy women with partners, the composite and dimension scores (D1, D3, and D5) decreased significantly with increasing age (p < 0.05). In comparison, surgically menopausal women had significantly lower composite and dimension scores (p < 0.001), with the exception of D7, which was significantly higher (more problems). As a percent of the normative means for healthy women with partners, the dimension scores for surgically menopausal women were lowest for D1--47.2%, D3--46.9%, and D5--46.1%. This research provides further validation of the BISF-W as an instrument for evaluating female sexual function and quantifies the nature and degree of impaired sexual function in surgically menopausal women.
Article
A large component of women's sexual desire is responsive rather than spontaneous. Therefore, women's motivation and ability to find and respond to sexual stimuli to experience sexual arousal and subsequent sexual desire is crucial, but complex. In ongoing relationships, a woman's motivation appears to be largely influenced by her emotional intimacy with her partner and her wish to enhance it. Drugs (including androgen replacement therapy) aimed at increasing women's spontaneous sexual wanting (less characteristic of women in long-term relationships) or their arousability may have a role if other psychologic factors affecting arousability are addressed in tandem. A woman's sexual arousal is composite and complex, correlating well with how mentally exciting she finds the sexual stimulus and its context and poorly with objective genital blood flow changes. Drugs aimed at increasing the latter, including phosphodiesterase inhibitors, may have a role if there is prior careful enquiry as to whether genital engorgement is present but not attended to or is physically absent. Psychophysiologic studies to date suggest the former is common in women presenting with arousal disorder.
Article
Objective: To consider explanations for the inconsistent evidence concerning behavioral effects of androgens in women. The following possible explanatory mechanisms are explored: [1] Women vary in their behavioral responsiveness to T. [2] Some reported effects of exogenous T may be induced by increasing bioavailable estrogen. [3] Sexual effects of T may be secondary to direct effects on mood. [4] The relationship between T and sexuality is readily obscured by psychological mechanisms. [5] Stress-induced increases in adrenal androgens may further confuse the picture. [6] Women who respond to T respond to levels that are ineffective in men. There is no evidence of a threshold in women above which further increases in T have no additional effect. Conclusion(s): A theoretical model, involving desensitization of the central nervous system to T during early development in the male, is presented as a possible explanation for some of these relevant differences between men and women and for much of the conflicting evidence in the literature on women.
Sildenafil citrate (Viagra Pfizer, New York, NY) is indicated for the treatment of erectile dysfunction in men. The nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) involved in penile erection and enhanced by sildenafil may also play a role in some components of the female sexual arousal response. The efficacy and safety of sildenafil were evaluated in estrogenized and estrogen-deficient women with sexual dysfunction that included female sexual arousal disorder (FSAD). Patients were randomized to receive 10-100 mg sildenafil or matching placebo. To assess efficacy, patients completed two global efficacy questions (GEQ), the Life Satisfaction Checklist (LSC), an event log of sexual activity, and a 31-item sexual function questionnaire (SFQ). To assess safety, adverse event (AE) data were recorded. A total of 577 estrogenized and 204 estrogen-deficient women were randomized to treatment. All were diagnosed with FSAD, but it was the primary presenting symptom in only 46% and 50% of women, respectively. Differences in efficacy between sildenafil and placebo were not significant for any patient or partner end points (e.g., the two GEQ, the sexual event logs, the LSC, and the SFQ). The main AE were headache, flushing, rhinitis, nausea, visual disturbances, and dyspepsia, which were generally mild to moderate in nature. Any genital physiological effect of sildenafil was not perceived as improving the sexual response in estrogenized or estrogen-deficient women with a broad spectrum of sexual dysfunction that included FSAD. Whether more specific subgroups of women with FSAD could potentially benefit from treatment with sildenafil is an area for future research.
Article
In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire. Double-blind randomized trial. Healthy volunteers in a multicenter research environment. Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire. 4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107). Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire. Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated. Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.
Article
Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, increases rhabdosphincter contractility via the stimulation of pudendal motor neuron alpha-1 adrenergic and 5-hydroxytryptamine-2 receptors. In this first phase 3 study we assessed the efficacy and safety of duloxetine in women with stress urinary incontinence (SUI). A total of 683 North American women 22 to 84 years old were enrolled in this double-blind, placebo controlled study. The case definition included a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) of 7 or greater, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress test and stress pad test. After a 2-week placebo lead-in period subjects were randomly assigned to receive placebo (339) or 80 mg duloxetine daily (344) as 40 mg twice daily for 12 weeks. Primary outcome variables included IEF and an incontinence quality of life questionnaire. Van Elteren's test was used to analyze percent changes in IEF with a stratification variable of weekly baseline IEF (less than 14 and 14 or greater). ANCOVA was used to analyze incontinence quality of life scores. Mean baseline IEF was 18 weekly and 436 subjects (64%) had a baseline IEF of 14 or greater. There was a significant decrease in IEF with duloxetine compared with placebo (50% vs 27%, p <0.001) with comparably significant improvements in quality of life (11.0 vs 6.8, p <0.001). Of subjects on duloxetine 51% had a 50% to 100% decrease in IEF compared with 34% of those on placebo (p <0.001). These improvements with duloxetine were associated with a significant increases in the voiding interval compared with placebo (20 vs 2 minutes, p <0.001) and they were observed across the spectrum of incontinence severity. The discontinuation rate for adverse events was 4% for placebo and 24% for duloxetine (p <0.001) with nausea the most common reason for discontinuation (6.4%). Nausea, which was also the most common side effect, tended to be mild to moderate and transient, usually resolving after 1 week to 1 month. Of the 78 women who experienced treatment emergent nausea while taking duloxetine 58 (74%) completed the trial. These phase 3 data are consistent with phase 2 data and they provide further evidence for the safety and efficacy of duloxetine as a pharmacological agent for the treatment of women with SUI.
Article
The Profile of Female Sexual Function (PFSF) is a patient-based instrument for the measuring of loss of sexual function in menopausal women with low libido (hypoactive female sexual desire disorder). The instrument, which contains 37 items in seven domains (sexual desire, arousal, orgasm, sexual pleasure, sexual concerns, sexual responsiveness, and sexual self-image) and a single-item measure of overall satisfaction with sexuality, has been extensively developed and initially validated in over 500 oophorectomized women with low libido in North America, Europe, and Australia. Initial validation results showed the PFSF is capable of discriminating these patients from age-matched controls and produced consistent responses and sensitivity across geographies. The objective of this nonrandomized, parallel-group study was to examine the psychometric properties of the final PFSF in an independent group of surgically menopausal women with low libido and to extend validation to naturally menopausal women with low libido. Participants from 16 study centers in North America included surgically (n = 59) and naturally (n = 88) menopausal women with low libido and their age-matched control subjects, both premenopausal (n = 57) and naturally menopausal (n = 47), who reported no problems with libido. Subjects completed the PFSF at baseline and again 4 weeks later. Adjusted mean scores for each of the seven domains were statistically significantly lower (P < 0.0001) in surgically menopausal women with low libido compared with age-matched control women, and in naturally menopausal women with low libido compared with naturally menopausal control women, demonstrating excellent discriminant validity. Test-retest reliability ranged from 0.57 to 0.91 for the seven domain scores, whereas internal-consistency reliability ranged from 0.74 to 0.95. Results of this research support the conclusion that the PFSF is a valid and reliable instrument for measurement of loss of sexual function in both naturally and surgically menopausal women with low libido.
Article
Androgens have important physiological effects in women. Postmenopausal androgen replacement, most commonly as testosterone therapy, is becoming increasingly widespread. This is despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety data. With respect to the breast specifically, there is the potential for exogenous testosterone to exert either androgenic or indirect estrogenic actions, with the latter potentially increasing breast cancer risk. In experimental studies, androgens exhibit growth-inhibitory and apoptotic effects in some, but not all, breast cancer cell lines. Differing effects between cell lines appear to be due primarily to variations in concentrations of specific coregulatory proteins at the receptor level. In rodent breast cancer models, androgen action is antiproliferative and proapoptotic, and is mediated via the androgen receptor, despite the potential for testosterone and dehydroepiandrosterone to be aromatized to estrogen. The results from studies in rhesus monkeys suggest that testosterone may serve as a natural endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium. Epidemiological studies have significant methodological limitations and provide inconclusive results. The strongest data for exogenous testosterone therapy comes from primate studies. Based on such simulations, inclusion of testosterone in postmenopausal estrogen-progestin regimens has the potential to ameliorate the stimulating effects of combined estrogen-progestin on the breast. Research addressing this is warranted; however, the number of women that would be required for an adequately powered randomized controlled trial renders such a study unlikely.
Article
The purpose of this study was to develop a self-administered, patient-based questionnaire to assess loss of sexual desire and associated symptoms in postmenopausal women with hypoactive sexual desire disorder (HSDD) experiencing distress. Preliminary items and domains of sexual function were identified through individual and focus group interviews with postmenopausal women in the United States and Europe. A subset of items was selected for translation and further analysis. Cognitive interviews were conducted with women with HSDD and non-HSDD women in eight countries to ensure items would have the same meaning in seven languages. The resulting instrument was tested in 325 oophorectomized women with HSDD and 255 age-matched nonoophorectomized control women in the United States, Canada, Europe, and Australia. Psychometric item reduction analyses resulted in 37 items organized into seven domains characterizing female sexual function in postmenopausal women with HSDD. Excellent reliability and validity of the domains of the Profile of Female Sexual Function (PFSF) were observed in all geographic areas tested. Statistically significant differences between oophorectomized women with low libido and control women were found for all domains and all geographic areas. The PFSF is a new instrument specifically designed for measurement of sexual desire in oophorectomized women with low libido. Robust psychometric properties have been established in a large number of geographic regions and languages, making it useful for assessing therapeutic change in multinational clinical trials.
Article
The aim of this study was to assess the effect of alosetron on bowel urgency and irritable bowel syndrome (IBS) global improvement in diarrhea-predominant IBS (D-IBS). Women with a lack of satisfactory bowel urgency control at least 50% of the time during screening were randomized to receive alosetron 1 mg (n = 246) or placebo (n = 246) twice daily. The primary end point was the percentage of days with satisfactory control of bowel urgency. The response rate for the IBS global improvement scale (GIS) was a secondary end point. GIS responders were patients who recorded either moderate or substantial improvement in IBS symptoms relative to the way they felt before entering the study. Other end points included improvement in stool frequency, stool consistency, and percentage of days with incomplete evacuation. Further analyses were performed on a subset of patients who had at least 10 of 14 days during screening (>/=71% of days) with a lack of satisfactory control of bowel urgency. Patients had severe chronic IBS symptoms, and 89% of patients had D-IBS. Alosetron resulted in a greater percentage of days with satisfactory control of urgency compared with placebo (69% vs. 56%, respectively, P < 0.001). Greater percentages of alosetron-treated patients were GIS responders at 4, 8, and 12 weeks compared with placebo (59% vs. 41%, 63% vs. 41%, and 68% vs. 46%, respectively, P < 0.001). Patients with more frequent urgency had similar results. Constipation occurred in 28% and 9% of subjects in the alosetron- and placebo-treated groups, respectively. No cases of ischemic colitis were reported. Alosetron effectively manages bowel urgency and improves global symptoms in women with severe chronic D-IBS.
Article
There is now convincing evidence that usual hormone therapy for ovarian failure increases the risk for breast cancer. We have previously shown that ovarian androgens normally protect mammary epithelial cells from excessive estrogenic stimulation, and therefore we hypothesized that the addition of testosterone to usual hormone therapy might protect women from breast cancer. This was a retrospective, observational study that followed 508 postmenopausal women receiving testosterone in addition to usual hormone therapy in South Australia. Breast cancer status was ascertained by mammography at the initiation of testosterone treatment and biannually thereafter. The average age at the start of follow-up was 56.4 years, and the mean duration of follow-up was 5.8 years. Breast cancer incidence in this group was compared with that of untreated women and women using usual hormone therapy reported in the medical literature and to age-specific local population rates. There were seven cases of invasive breast cancer in this population of testosterone users, for an incidence of 238 per 100,000 woman-years. The rate for estrogen/progestin and testosterone users was 293 per 100,000 woman-years--substantially less than women receiving estrogen/pro-gestin in the Women's Health Initiative study (380 per 100,000 woman-years) or in the "Million Women" Study (521 per 100,000 woman-years). The breast cancer rate in our testosterone users was closest to that reported for hormone therapy never-users in the latter study (283 per 100,000 woman-years), and their age-standardized rate was the same as for the general population in South Australia. These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population.
Article
Changes in androgen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established. The objective of this study was to document the effects of age on androgen levels in healthy women and to explore the effects of natural and surgical menopause. A cross-sectional study was conducted of 1423 non-healthcare-seeking women, aged 18-75 yr, randomly recruited from the community over 15 months. Serum levels by age of total testosterone (T), calculated free T, dehydroepiandrosterone sulfate, and androstenedione in a reference group of women free of confounding factors. Women in the reference group had no usage of exogenous steroid therapy; no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and no hyperprolactinemia or polycystic ovarian syndrome. The effects of natural and surgical menopause on sex steroid levels were also examined. In the reference population (n = 595), total T, calculated free T, dehydroepiandrosterone sulfate, and androstenedione declined steeply with age (P < 0.001), with the decline of each being greater in the earlier than the later decades. Examination of serum androgen levels by year in women aged 45-54 yr showed no independent effect of menopausal status on androgen levels. In women aged 55 yr or older, those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group. We report that serum androgen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production. These significant variations in androgens with age must be taken into account when normal ranges are reported and in studies of the role of androgens in women.
Article
To assess the efficacy and safety of a 300 mug/d testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women on concomitant estrogen therapy. Five hundred thirty-three women with hypoactive sexual desire disorder who had undergone previous hysterectomy and bilateral oophorectomy were enrolled in a 24-week, multicenter, double-blind, placebo-controlled trial. Patients were randomly assigned to receive placebo or the testosterone patch twice weekly. The primary efficacy endpoint was change from baseline at week 24 in the frequency of total satisfying sexual activity, measured by the Sexual Activity Log. Secondary measures included sexual desire using the Profile of Female Sexual Function and personal distress as measured by the Personal Distress Scale. Hormone levels, adverse events, and clinical laboratory measures were reviewed. Total satisfying sexual activity significantly improved in the testosterone patch group compared with placebo after 24 weeks (mean change from baseline, 1.56 compared with 0.73 episodes per 4 weeks, P = .001). Treatment with the testosterone patch also significantly improved sexual desire (mean change, 10.57 compared with 4.29, P < .001) and decreased personal distress (P = .009). Serum free, total, and bioavailable testosterone concentrations increased from baseline. Overall, adverse events were similar in both groups (P > .05). The incidence of androgenic adverse events was higher in the testosterone group; most androgenic adverse events were mild. In surgically menopausal women with hypoactive sexual desire disorder, a 300 mug/d testosterone patch significantly increased satisfying sexual activity and sexual desire, while decreasing personal distress, and was well tolerated through up to 24 weeks of use.