Neuroendocrine aberrations in women with hypothalamic amenorrhea
ABSTRACT To further elucidate the neuroendocrine regulation of anterior pituitary function in women with functional hypothalamic amenorrhea (FHA), we measured serum LH, FSH, cortisol, GH, PRL, TSH concentrations simultaneously at frequent intervals for 24 h in 10 women with FHA and in 10 normal women in the early follicular phase (NC). Using the same data, we separately analyzed the cortisol-PRL responses to meals in these women. In addition, the pituitary responses to the simultaneous administration of GnRH, CRH, GHRH, and TRH were assessed in 6 FHA and 6 normal women. The 24-h secretory pattern of each hormone except TSH was altered in the women with FHA. Compared to normal women, the women with FHA had a 53% reduction in LH pulse frequency (P less than 0.0001) and an increase in the mean LH interpulse interval (P less than 0.01); LH pulse amplitude was similar. The 24-h integrated LH and FSH concentrations were reduced 30% (P = 0.01) and 19% (P less than 0.05), respectively. The mean cortisol pulse frequency, amplitude, interpulse interval, and duration were similar in the two groups, but integrated 24-h cortisol secretion was 17% higher in the women with FHA (P less than 0.05). This increase was greatest from 0800-1600 h, but also was present from 2400-0800 h. Cortisol levels were similar in the two groups from 1600-2400 h, resulting in an amplified circadian excursion. In contrast, the 24-h serum PRL levels were markedly lower at all times (P less than 0.0001), the sleep-associated nocturnal elevation of PRL was proportionately greater (P less than 0.05), and serum GH levels were increased at night in the women with FHA (P less than 0.05). Although 24-h serum TSH levels were similar at all times, T3 (P less than 0.05) and T4 (P less than 0.01) levels were lower in the FHA women. The responses of serum cortisol to lunch (P less than 0.01) and dinner (P less than 0.05) and those of serum PRL to lunch (P less than 0.05) and dinner (P = 0.08) were blunted in the women with FHA. Pituitary hormone increments in response to the simultaneous iv administration of GnRH, CRH, GHRH, and TRH were similar in the two groups, except for a blunted PRL response to TRH in the women with FHA (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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- "FHA is caused by an alteration in gonadotropin-releasing hormone pulsatility,48 which in turn causes a disruption of luteinizing hormone pulses from the pituitary and gonadal steroid release from the ovaries.86 It reflects a state of estrogen deficiency, which may be one of the causes of decreased BMD.85 FHA may also be associated with several physiological changes, including overactivity of the hypothalamic-pituitary-adrenal axis (causing an increase in cortisol release) and disturbances of the hypothalamic-pituitary-thyroid axis (resulting in a “sick euthyroid” pattern).21 Leptin, a cytokine expressed by adipose tissue and strongly associated with fat mass, is lower in the amenorrheic athlete, most likely due to changes in body composition, particularly a decrease in fat mass.28 "
Article: The Female Athlete Triad[Show abstract] [Hide abstract]
ABSTRACT: The female athlete triad (the triad) is an interrelationship of menstrual dysfunction, low energy availability (with or without an eating disorder), and decreased bone mineral density; it is relatively common among young women participating in sports. Diagnosis and treatment of this potentially serious condition is complicated and often requires an interdisciplinary team. Articles from 1981 to present found on PubMed were selected for review of major components of the female athlete triad as well as strategies for diagnosis and treatment of the conditions. The main goal in treatment of young female athletes with the triad is a natural return of menses as well as enhancement of bone mineral density. While no specific drug intervention has been shown to consistently improve bone mineral density in this patient population, maximizing energy availability and optimizing vitamin D and calcium intake are recommended. Treatment requires a multidisciplinary approach involving health care professionals as well as coaches and family members. Prevention of this condition is important to minimize complications of the female athlete triad.07/2012; 4(4):302-11. DOI:10.1177/1941738112439685
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- "(2) The precocious atherosclerosis that characterizes subordinate females likely results from a subclinical stress-induced, reversible ovarian impairment that resembles functional hypothalamic amenorrhea/anovulation (FHA) observed in women [165,166]. This hypothesis is supported by the observation that ovariectomy eliminates the protection of dominant females, rendering them equivalent to subordinate females and males in atherosclerosis extent [165,167]. "
ABSTRACT: Cardiovascular disease remains the primary cause of death worldwide. In the US, deaths due to cardiovascular disease for women exceed those of men. While cultural and psychosocial factors such as education, economic status, marital status and access to healthcare contribute to sex differences in adverse outcomes, physiological and molecular bases of differences between women and men that contribute to development of cardiovascular disease and response to therapy remain underexplored. This article describes concepts, methods and procedures to assist in the design of animal and tissue/cell based studies of sex differences in cardiovascular structure, function and models of disease. To address knowledge gaps, study designs must incorporate appropriate experimental material including species/strain characteristics, sex and hormonal status. Determining whether a sex difference exists in a trait must take into account the reproductive status and history of the animal including those used for tissue (cell) harvest, such as the presence of gonadal steroids at the time of testing, during development or number of pregnancies. When selecting the type of experimental animal, additional consideration should be given to diet requirements (soy or plant based influencing consumption of phytoestrogen), lifespan, frequency of estrous cycle in females, and ability to investigate developmental or environmental components of disease modulation. Stress imposed by disruption of sleep/wake cycles, patterns of social interaction (or degree of social isolation), or handling may influence adrenal hormones that interact with pathways activated by the sex steroid hormones. Care must be given to selection of hormonal treatment and route of administration. Accounting for sex in the design and interpretation of studies including pharmacological effects of drugs is essential to increase the foundation of basic knowledge upon which to build translational approaches to prevent, diagnose and treat cardiovascular diseases in humans.12/2011; 2(1):14. DOI:10.1186/2042-6410-2-14
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- "In conclusion, the current findings corroborate our previous account of diminished serotonin response to citalopram, inferred from changes in prolactin, in gonadally intact s-variant females (Hoffman, et al., 2007) and extend these data by showing that this effect of 5HTTLPR is most evident when both ovarian steroid hormones, estradiol and progesterone, are restored to follicular and luteal phase concentrations, respectively. Importantly, these data suggest that clinicians should be aware of ovarian status in patients being considered for treatment with serotoninergic agents, as the hypogonadism associated with chronic psychosocial stressors in women (Berga et al., 1989) might decrease responsiveness to SSRI treatment. It is also possible that accounting for hormones in pre-, peri-, and postmenopausal women could explain some of the variability surrounding the efficacy of SSRIs in responders and non-responders to pharmacotherapy in women. "
ABSTRACT: Individual vulnerability to psychopathologies is linked to a number of genetic polymorphisms including the serotonin transporter (5HTT) promoter polymorphic region (5HTTLPR). A single copy of the short variant (s-variant) allele of 5HTTLPR confers increased susceptibility to anxiety disorders and depression and decreased efficacy of serotonin-releasing agents in pharmacotherapy compared to the homozygous long 5HTTLPR variant (l/L). The data suggesting that the 5HTTLPR polymorphism modulates the efficacy of serotonin-releasing agents in pharmacotherapy is inconsistent. Other factors such as age, gender, and hormonal status could interact with 5HTTLPR genotype to affect individual physiological and behavioral responses to serotonin reuptake inhibitors such as citalopram. Indeed, estradiol and progesterone, the primary female steroid hormones, exert an array of effects on the serotonergic system, including 5HTT expression. The present study used ovariectomized female rhesus monkeys to determine the interaction between the 5HTTLPR polymorphism and the effects of midfollicular levels of estradiol and luteal levels of progesterone on serotonergic responsivity to acute citalopram administration. The increase in serum prolactin, a surrogate measure of serotonin activity, following citalopram administration was significantly larger in l/L females than in s-variant females over the course of two hours during concurrent estradiol and progesterone hormone replacement only. These data suggest that ovarian function and the 5HTTLPR polymorphism interact to gate serotonergic reactivity in females, suggesting that clinicians should be aware of the ovarian status and 5HTTLPR genotype of women when considering serotonergic pharmacotherapy in women.Experimental and Clinical Psychopharmacology 08/2011; 19(6):401-8. DOI:10.1037/a0025008 · 2.63 Impact Factor