Reversible alopecia associated with high blood mercury levels and early menopause: a report of two cases.

OBJECTIVE: The aim of this study was to report on two women in early menopause with alopecia and high mercury (Hg) levels which reversed with a decrease in toxic levels. METHODS: Retrospective chart review and case studies in a reproductive endocrinology practice. RESULTS: A 43-year-old woman initially evaluated for early menopause later experienced sudden circumscribed hair loss on the scalp. Blood tests indicated elevated Hg levels and further investigation revealed a diet high in tuna. Levels fell with elimination of dietary tuna. Another woman, 39 years old was complaining of severe hot flashes, night sweats, and menstrual irregularity also developed alopecia. Treated unsuccessfully for low testosterone, blood tests indicated high Hg levels and simultaneous hair loss was observed; recommendation to alter diet, including fish intake, was followed by a reversal of alopecia, along with a decrease in blood Hg levels. Literature searches were conducted with a focus on Hg toxicity or poisoning with symptom of alopecia. CONCLUSIONS: Women of reproductive age frequently seek treatment for what is thought to be hormone-related hair loss especially at menopause. Two women demonstrated a strong temporal correlation to high Hg levels associated with early menopause, which was reversible. The development of alopecia in the setting of mild Hg intoxication has not been reported in the medical literature despite its appearance in the popular press. Measurement of Hg levels should be considered in women with alopecia and its relationship to early menopause is unclear but bears further research.

Exercise-induced amenorrhea and bone health in the adolescent athlete.

Female participation in high school athletics has increased 800% in the last 30 years. The problem of exercise-induced amenorrhea was initially thought to be analogous to hypoestrogenism, but recent studies suggest that nutritional issues underlie most of the pathophysiology and that the mechanism is different from that seen in the primary hypogonadal state. Exercise-induced amenorrhea can be an indicator of an energy drain, and the presence of the other components of the female athlete triad-bone density loss and eating disorders-must be determined as well. Addressing skeletal problems related to nutritional and hormonal deficiencies in this population is of very high priority.

Is megestrol acetate a suitable option for treatment of hot flashes in women with breast cancer?

Chemotherapy for breast cancer is associated with the development of hot flashes, which can cause the patient considerable discomfort. Estrogen replacement therapy alleviates the number and severity of hot flashes but is contraindicated in such cases. Alternative methods to treat hot flashes are, therefore, urgently needed. Goodwin et al. have performed a 6-month, double-blind, randomized, placebo-controlled trial of megestrol acetate in 286 women with breast cancer. After 3 months, 65% of the patients receiving 20 mg megestrol acetate daily had achieved an appreciable reduction in the number of hot flashes (> or = 75% from baseline), compared with 48% in the 40 mg megestrol acetate group and 14% in the placebo group. The positive effects of megestrol acetate on hot flash frequency were maintained at 6 months. In this Practice Point commentary, I discuss the key findings of Goodwin et al. and place them into clinical context, highlighting the need for additional studies of hormonal therapies in women with breast cancer.

Coping with social stress: implications for psychopathology in young adolescent girls.

This study investigated the impact of social stress on symptoms of psychopathology at the entry into adolescence (111 girls, Mage = 11.84, SD = 0.77). We examined whether peer stress and pubertal timing were associated with internalizing distress and aggression, and whether responses to stress and cortisol reactivity mediated or moderated these associations. Cortisol samples were collected from saliva samples during in-home visits, and the YSR was used to assess psychopathology. Interestingly, pubertal timing demonstrated a trend association with cortisol. Responses to stress mediated the association between social stress and symptoms of internalizing distress and aggression. Specifically, early maturers and girls with higher levels of peer stress exhibited more problematic responses to stress, in turn demonstrating higher levels of internalizing distress and aggression. Significant moderation effects also emerged. For example, early maturers who experienced higher levels of emotional/cognitive numbing in response to peer stress were at greater risk for aggression. Findings identify coping strategies that may be used in evidence-based programming to help girls transition more successfully into adolescence will be discussed.

Role of exercise and nutrition in menopause.

Menopause and the aging process itself cause many physiologic changes, which explain the increased prevalence of chronic diseases observed in postmenopausal women. Exercise and nutrition play important roles in the prevention and treatment of cardiovascular disease, cancer, obesity, diabetes, osteoporosis, and depression.

Effects of oral conjugated equine estrogens with or without medroxyprogesterone acetate on incident hypertension in the Women's Health Initiative hormone therapy trials.

OBJECTIVE: The aim of the study was to determine the effect of menopausal hormone therapy on incident hypertension in the two Women's Health Initiative hormone therapy trials and in extended postintervention follow-up. METHODS: A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. This analysis includes the subsample of 18,015 women who did not report hypertension at baseline and were not taking antihypertensive medication. Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 5,994) or placebo (n = 5,679). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 3,108) or placebo (n = 3,234). The intervention lasted a median of 5.6 years in the CEE plus MPA trial and 7.2 years in the CEE-alone trial with 13 years of cumulative follow-up until September 30, 2010. The primary outcome for these analyses was self-report of a new diagnosis of hypertension and/or high blood pressure requiring treatment with medication. RESULTS: During the CEE and CEE plus MPA intervention phase, the rate of incident hypertension was 18% higher for intervention than for placebo (CEE: hazard ratio [HR], 1.18; 95% CI, 1.09-1.29; CEE plus MPA: HR, 1.18; 95% CI, 1.09-1.27). This effect dissipated postintervention in both trials (CEE: HR, 1.06; 95% CI, 0.94-1.20; CEE plus MPA: HR, 1.02; 95% CI, 0.94-1.10). CONCLUSIONS: CEE (0.625 mg/d) administered orally, with or without MPA, is associated with an increased risk of hypertension in older postmenopausal women. Whether lower doses, different estrogen formulations, or transdermal route of administration offer lower risks warrant further study.

Treatment of anorexia nervosa is associated with increases in bone mineral density, and recovery is a biphasic process involving both nutrition and return of menses.

BACKGROUND: Recovery from osteoporosis in anorexia nervosa (AN) is uncertain. OBJECTIVE: The purpose of this study was to understand the changes in bone mineral density (BMD) in women with AN and the mechanisms of recovery from osteopenia. DESIGN: We studied BMD and markers of bone formation and resorption, osteocalcin and N-telopeptide (NTX), in patients with AN (n=28) who were following a behavioral weight-gain protocol. RESULTS: Anorexic patients experienced significant percentage increases in BMD (4.38 +/- 7.48% for spine; 3.77 +/- 8.8% for hip; P<0.05 for both) from admission until recovery of 90% ideal body weight, achieved over 2.2 mo. NTX concentrations were higher in patients with AN at admission than in healthy control subjects (n=11; 69.0 +/- 31.09 and 48.3 +/- 14.38 nmol/mmol creatinine, respectively; P<0.05) and in reference control subjects (n=30; 69.0 +/- 31.09 and 37.0+/-6.00 nmol/mmol creatinine, respectively; P<0.001). In weight-recovered subjects with AN, osteocalcin increased (from 8.0 +/- 3.05 to 11.2 +/- 6.54 ng/mL; P<0.05), whereas NTX remained elevated (from 69.0 +/- 31.09 to 66.7 +/- 45.5 nmol/mmol creatinine; NS). A decrease in NTX (from 70.7 +/- 40.84 to 45.9 +/- 22.72 nmol/mmol creatinine; NS) occurred only in the subgroup of subjects who regained menses with weight recovery. CONCLUSIONS: Nutritional rehabilitation induces a powerful anabolic effect on bone. However, a fall of NTX and a shift from the dominant resorptive state, which we postulate involves full recovery, may involve a hormonal mechanism and require a return of menses. Nutritional rehabilitation appears to be critical to bone recovery and may explain the ineffectiveness of estrogen treatment alone on BMD in the cachectic state.

Historical perspectives in postmenopausal hormone therapy: defining the right dose and duration.

Recommended dosages of postmenopausal estrogen therapy (ET) and estrogen-progestin therapy (EPT), like those of oral contraceptives, have decreased markedly since oral estrogens were first introduced. Recently, the movement toward lower doses of ET/ EPT has accelerated because of the results of the Women's Health Initiative, which showed that lower-dose ET/EPT may provide similar efficacy and an improved safety profile compared with higher-dose preparations. For example, lower ET/EPT doses effectively relieve vasomotor and vulvovaginal symptoms associated with menopause, prevent bone loss, protect the endometrium, and are better tolerated than commonly prescribed doses. Current guidelines suggest the use of the lowest effective dose for the shortest duration consistent with treatment goals, benefits, and risks for the individual woman. However, the impact of treatment discontinuation should be considered when advising women to use hormone therapy for relieving menopausal symptoms for the shortest possible duration.

American College of Sports Medicine position stand. The female athlete triad.

The female athlete triad (Triad) refers to the interrelationships among energy availability, menstrual function, and bone mineral density, which may have clinical manifestations including eating disorders, functional hypothalamic amenorrhea, and osteoporosis. With proper nutrition, these same relationships promote robust health. Athletes are distributed along a spectrum between health and disease, and those at the pathological end may not exhibit all these clinical conditions simultaneously. Energy availability is defined as dietary energy intake minus exercise energy expenditure. Low energy availability appears to be the factor that impairs reproductive and skeletal health in the Triad, and it may be inadvertent, intentional, or psychopathological. Most effects appear to occur below an energy availability of 30 kcal.kg(-1) of fat-free mass per day. Restrictive eating behaviors practiced by girls and women in sports or physical activities that emphasize leanness are of special concern. For prevention and early intervention, education of athletes, parents, coaches, trainers, judges, and administrators is a priority. Athletes should be assessed for the Triad at the preparticipation physical and/or annual health screening exam, and whenever an athlete presents with any of the Triad's clinical conditions. Sport administrators should also consider rule changes to discourage unhealthy weight loss practices. A multidisciplinary treatment team should include a physician or other health-care professional, a registered dietitian, and, for athletes with eating disorders, a mental health practitioner. Additional valuable team members may include a certified athletic trainer, an exercise physiologist, and the athlete's coach, parents and other family members. The first aim of treatment for any Triad component is to increase energy availability by increasing energy intake and/or reducing exercise energy expenditure. Nutrition counseling and monitoring are sufficient interventions for many athletes, but eating disorders warrant psychotherapy. Athletes with eating disorders should be required to meet established criteria to continue exercising, and their training and competition may need to be modified. No pharmacological agent adequately restores bone loss or corrects metabolic abnormalities that impair health and performance in athletes with functional hypothalamic amenorrhea.

Anorexia, bulimia, and the athletic triad: evaluation and management.

Caloric restriction caused by undernutrition or over-exercise is increasingly common and has significant health consequences such as hypothalamic amenorrhea, infertility, attainment of low peak bone mass, and bone loss leading to fracture. In these patients, the pathophysiology of amenorrhea and bone loss is multifactorial, involving hormones that integrate the nutritional state with the hypothalamic-pituitary-ovarian axis, including leptin and possibly ghrelin. The pathophysiology of bone loss includes nutritional deficiencies, possibly estrogen deficiency, and direct and indirect effects of leptin on bone. Identifying patients at risk for low bone mineral density and fracture is important, as is screening with dual energy radiograph absorptiometry. Treatment has focused on oral contraceptive use, yet improved bone mineral density is marked by nutritional recovery and anovulation reversal. Therefore, resolving the nutrition deficiency should be the cornerstone of treatment. Cognitive-behavioral therapy aims for weight recovery, which can lead to reversal of amenorrhea and improvement in other associated metabolic abnormalities. During treatment, estradiol levels can be followed to assess hypothalamic-pituitary-ovarian recovery because estradiol secretion may increase well before ovulation occurs. In patients failing the above interventions, hormone replacement should be considered, but bone mineral density should be followed because patients may continue to lose bone despite treatment with oral contraceptives if nutrition is not improved.

Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline.

Cosponsoring Associations: The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. Objective: To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). Participants: The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. Conclusions: FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.

Appropriate use of estrogen replacement therapy in adolescents and young adults with Turner syndrome and hypopituitarism in light of the Women's Health Initiative.

Adolescents and young adult females who are hypoestrogenic need gonadal hormone therapy for sexual development, enhancement of growth, and maintenance of reproductive tissues, cyclic menses, and psychosocial health. In addition, prevention of chronic disease, specifically bone loss and possibly early heart disease, needs to be addressed in these patients. The etiology of hypopituitarism should also be considered when evaluating therapeutic options. The issues concerning estrogen replacement therapy (ERT), including the doses used and the length of therapy, are different for young patients than for postmenopausal women. The highly publicized findings of the Women's Health Initiative have identified risks of combined progestin-estrogen therapy; these risks, found in much older women, have raised questions regarding the appropriateness of ERT in adolescents with hypopituitarism and Turner syndrome. It is therefore appropriate to examine the relative risks and benefits of ERT in these populations.

Vaginal estrogen use and effects on quality of life and urogenital morbidity in postmenopausal women after publication of the Women's Health Initiative in New York City.

OBJECTIVE: In the years after the 2002 publication of results from the Women's Health Initiative study, there has been a reluctance to prescribe hormone therapy to symptomatic postmenopausal women and confusion over its duration and method of prescription. The main concerns are the risks of cardiovascular events and breast cancer. However, local vaginal estrogen (VE) may provide benefits without systemic effects. METHODS: This study investigates the use and effects of VE on quality of life and urogenital morbidity among women who stopped hormone therapy after the Women's Health Initiative and compares them with women who continued hormone therapy. Three groups were compared: group 1, women who have remained on HT/ET; group 2, women who have resumed HT/ET after stopping for at least 6 months, and group 3, women who have stopped HT/ET and have not resumed. RESULTS: Overall, ever use and present use of VE were most prevalent in women who reported dyspareunia (ever, P = 0.003; present, P = 0.005) and vaginal dryness (ever, P = 0.001; present, P = 0.004). VE use was significantly more probable for women in group 3 than for women in the other groups (group 3 [3.5%] vs. group 1 [17.7%] and group 2 [16.7%]; P = 0.002). Women in group 3 who used VE reported significantly higher sexual quality of life (using the sexual domain of the Utian Quality of Life Scale) compared with women in group 3 who did not use VE (P = 0.007). There was no difference in the incidence of urinary tract infections between the three groups (group 1, 22.9%; group 2, 26.3%; group 3, 25.5%). The percentage of women who were either married or living in a marriage-like relationship did not differ between the three groups (group 1, 68.4%; group 2, 78.6%; group 3, 78.8%). CONCLUSIONS: Women who report dyspareunia and vaginal dryness are more likely to use VE. Women who do not use systemic therapy but use VE score significantly higher on the sexual quality-of-life scale than women not using VE.

Body fat redistribution after weight gain in women with anorexia nervosa.

BACKGROUND: Body image distortions are a core feature of anorexia nervosa (AN). Increasing evidence suggests that the fat distribution immediately after weight restoration in patients with AN differs from the distribution typical of healthy adult women. OBJECTIVE: The purpose of this study was to assess body fat distribution before and shortly after normalization of weight in women with AN. DESIGN: Body composition and fat distribution were assessed by anthropometry, dual-energy X-ray absorptiometry, and whole-body magnetic resonance imaging in 29 women with AN before and after weight normalization and at a single time point in 15 female control subjects. Hormone concentrations were also evaluated in patients and control subjects. RESULTS: During approximately 10.1 +/- 2.9 wk (range: 4-17.3 wk) of treatment, patients with AN gained 12.2 +/- 3.6 kg, and refed weight (54.1 +/- 4.2 kg) did not differ significantly from that of control subjects (54.7 +/- 4.4 kg). Waist-to-hip circumference ratio (P < 0.006), total trunk fat (P < 0.003), visceral adipose tissue (P < 0.006), and intramuscular adipose tissue (P < 0.003) were significantly greater in the weight-recovered patients than in the control subjects. In contrast, after refeeding, total subcutaneous adipose tissue and skeletal muscle mass did not differ significantly between the patients and control subjects. In patients with AN, serum cortisol decreased and serum estradiol increased significantly with refeeding but not to control concentrations. CONCLUSIONS: In women with AN, normalization of weight in the short term is associated with an abnormal distribution of body fat. The implications of these findings for the long-term psychological and physical health of women with AN are unknown.

Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study.

OBJECTIVE: The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia. METHODS: After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35 microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles. RESULTS: For subjects completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism. CONCLUSIONS: Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.

Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels.

Osteopenia, which is correlated with amenorrhea and poor nutritional habits, has been well documented in elite ballet dancers. Estrogen replacement therapy and recovery from amenorrhea have not been associated with normalization of bone density. Thus, the osteopenia may be related to changes brought about by chronic dieting or other factors, such as a hypometabolic state induced by poor nutrition. The purpose of this study was to investigate the relationship of chronic dieting and resting metabolic rate (RMR) to amenorrhea and bone density. RMR, bone density, eating disorder assessments, leptin levels, and complete menstrual and medical histories were determined in 21 elite ballet dancers and in 27 nondancers (age, 20-30 yr). No significant correlations were found between high EAT26 scores, a measure of disordered eating, and RMR, bone densities, body weight, body fat, or fat-free mass. However, when RMR was adjusted for fat-free mass (FFM), a significant positive correlation was found between RMR/FFM and bone density in both the arms (P < 0.001) and spine (P < 0.05) in ballet dancers, but not in the normal controls. The dancers also demonstrated significantly higher EAT scores (22.9 +/- 10.3 vs. 4.1 +/- 2.4; P < 0.001) and lower RMR/FFM ratios (30.0 +/- 2.2 vs. 32.05 +/- 2.8; P < 0.01). The only variable to predict lower RMR/FFM in the entire sample was ever having had amenorrhea; this group had significantly higher EAT scores (18.0 +/- 13.5 vs. 10.3 +/- 10.2; P < 0.05), lower leptin levels (4.03 +/- 0.625 vs. 7.10 +/- 4.052; P < 0.05), and lower bone mineral density in the spine (0.984 +/- 0.11 vs. 1.10 +/- 0.13; P < 0.05) and arm (0.773 +/- 0.99 vs. 0.818 +/- 0.01; P < 0.05). We hypothesize that the correlation between low RMR and lower leptin levels and bone density may be more strongly related to nutritional habits in ballet dancers, causing significant depression of RMR, particularly for those with a history of amenorrhea.

Osteopenia in exercise-associated amenorrhea using ballet dancers as a model: a longitudinal study.

Few longitudinal studies have investigated the effects of amenorrhea and amenorrhea plus exercise on bone mineral density (BMD) of young women. We carried out a 2-yr comparison of dancers and nondancers, both amenorrheic and normal, that investigated the role of hypothalamic amenorrhea on bone in this context. We studied 111 subjects (mean age, 22.4 +/- 4.6 yr; age of menarche, 14.1 +/- 2.2 yr), including 54 dancers, 22 with hypothalamic amenorrhea, and 57 nondancers, 22 with hypothalamic amenorrhea. Detailed hormonal and nutritional data were obtained in all groups to determine possible causal relationship to osteoporosis. The amenorrheic groups, dancers and nondancers, both showed reduced BMD in the spine, wrist, and foot, which remained below controls throughout the 2 yr. Only amenorrheic dancers showed significant changes in spine BMD (12.1%; P < 0.05) but still remained below controls, and within this subgroup, only those with delayed menarche showed a significant increase. The seven amenorrheic subjects (three dancers and four nondancers) who resumed menses during the study showed an increase in spine and wrist BMD (17%; P < 0.001) without achieving normalization. Delayed menarche was the only variable that predicted stress fractures (P < 0.005), which we used as a measure of bone functional strength. Analysis of dieting and nutritional patterns showed higher incidence of dieting behavior in this group, as manifested by higher Eating Attitudes Test scores (16.3 +/- 2.00 vs. 11.5 +/- 1.45; P < 0.05) and higher fiber intakes (30.7 +/- 3.00 vs. 17.5 +/- 2.01 g/24 h; P < 0.001). We concluded that low bone mass occurs in young women with amenorrhea and delayed menarche, both exercisers and nonexercisers. Crucial bone mass accretion may be compromised by their reproductive and nutritional health.

Central causes of hypogonadism--functional and organic.

Whether caused by environmental factors, lesions, genetic mutations, drug interactions, or unknown origins, the path of the central causes of hypogonadism frequently leads back to the GnRH pulse generator. In some cases, the cause can be unequivocally traced to a single factor, such as some of the congenital syndromes previously described. In most instances, however, hypogonadism is occult or functional. Because of the wide spectrum and complexity of underlying causes, a definitive diagnosis, especially in functional causes of the disorder, is not always attainable.