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Biomedical subjects

Michelle P Warren

Publications and source records attributed to Michelle P Warren.

15 recordsLinked to original sources

Functional hypothalamic amenorrhea is associated with elevated ghrelin and disordered eating.

OBJECTIVE: To determine whether ghrelin, an orexigen released by the stomach, is elevated in women with hypothalamic amenorrhea who are of normal weight and whether this is associated with abnormal eating behaviors. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Twenty-seven women with functional hypothalamic amenorrhea (FHA) and 42 normally menstruating women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ghrelin and eating behavior. RESULT(S): Ghrelin was significantly elevated in FHA (648.4 +/- 92.0 pg/mL vs. controls 596.7 +/- 79.0 pg/mL), while leptin, although lower, was not significantly so (FHA 5.4 +/- 2.8 ng/mL vs. controls 6.4 +/- 3 ng/mL). Eating Attitudes Test (EAT) scores were also significantly elevated in FHA (15.3 +/- 10.6 vs. controls 10.3 +/- 8.4), particularly on the subscale that measured bulimic behaviors. However, FHA patients consumed significantly more kilocalories (1,930 kcal/day vs. 1,588 kcal/day). CONCLUSION(S): High ghrelin in women with FHA may be linked to abnormal dietary behaviors, as reflected in high EAT scores yet characterized by normal caloric intake. Ghrelin may act as a restraining metabolic signal preventing a return to cyclicity in women with both disordered eating and FHA, prolonging amenorrhea when leptin has returned to normal.

Adult↗

Estrogen and exercise may be related to body fat distribution and leptin in young women.

OBJECTIVE: To evaluate the effects of estrogen deficiency and exercise on body composition and leptin in young women. DESIGN: Cross-sectional clinical study. SETTING: Volunteers in an academic research environment. PATIENT(S): Three age- and body mass index-matched groups: normal-weight women with exercise-associated amenorrhea, regularly menstruating exercising control women, and regularly menstruating normally active control women. INTERVENTION(S): Collection of blood samples and measurement of body fat and regional fat distribution by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURE(S): Central fat accumulation (i.e., ratio of trunk to extremity fat) and serum concentrations of E(2) and leptin. RESULT(S): In both regularly menstruating control groups, but not in the amenorrheic women, there was a negative correlation between the serum E(2) concentrations and the trunk-to-extremity fat ratio (r = -0.4), independent of age, exercise, body fat, and serum T concentrations. In all women, E(2) concentrations were positively and exercise inversely correlated to leptin concentrations, independent of body fat. CONCLUSION(S): Estradiol level is inversely associated with central fat accumulation only in women with regular menstrual cycles. In all young premenopausal subjects, estrogen secretion influences leptin concentrations independently of body fat.

Adipose Tissue↗

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.

Adolescent↗

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.

Absorptiometry, Photon↗

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.

Absorptiometry, Photon↗

The female athlete and menstrual function.

PURPOSE OF REVIEW: In the past year, there have been remarkable advancements in the understanding of the female athlete's pathology and in recognizing the specific needs of women participating in both recreational and competitive sports. The purpose of this review is to highlight the recent developments in the field of female athletes and menstrual function. RECENT FINDINGS: Although the female athletic triad, consisting of disordered eating, amenorrhea and osteoporosis, has been clinically recognized, there have been few studies quantifying the long-term effects. This review summarizes recently explored topics, including: disordered eating as a main culprit of menstrual irregularities, long-term longitudinal studies following female athletes through to retirement, and current treatment options. SUMMARY: Understanding the causes, profiles and the prevention of menstrual irregularities in the female athlete should help decrease its prevalence among women involved in athletics. The literature reviewed in this article stresses the importance of early detection, as well as the consequences of eating disorders, menstrual disturbances and bone loss left untreated.

Amenorrhea↗

A comparative review of the risks and benefits of hormone replacement therapy regimens.

The Women's Health Initiative (a large, randomized, placebo-controlled trial) investigated the effect of conjugated equine estrogens combined with medroxyprogesterone acetate on specific potential long-term benefits and risks. A review of the clinical studies that have investigated different types and regimens of estrogens combined with progestins was conducted to assess how applicable the results of the Women's Health Initiative are to hormone replacement therapy regimens in general. The studies that were reviewed were limited to randomized clinical trials and observational studies that have been published over the last 15 years (1987-2002) and to meta-analyses and reviews that may have included the literature before 1987. The increased risks for venous thromboembolism, stroke, coronary heart disease, and breast cancer that were identified in the Women's Health Initiative trial have also been reported with postmenopausal hormone therapies that contain a variety of estrogen and progestin products. The beneficial effects that were noted in the Women's Health Initiative, with respect to reductions in fractures and colorectal cancer, have not been evaluated in large, randomized controlled trials that use different estrogen/progestin combinations; however, observational trials that used a variety of estrogen or hormone replacement therapy products and randomized clinical studies that evaluated bone mineral density (an excellent predictor of fracture risk) with different estrogen/hormone replacement therapy regimens would suggest that results would be similar to those found in the Women's Health Initiative. Although the relief of menopausal symptoms, the primary reason women seek treatment, was not included in the overall benefit/risk analysis of the Women's Health Initiative, numerous trials suggest that all therapies are effective. Overall, these data indicate that the benefit/risk analysis that was reported in the Women's Health Initiative can be generalized to all postmenopausal hormone replacement therapy products.

Breast Neoplasms↗

Hormone replacement therapy: controversies, pros and cons.

Hormone replacement therapy (HRT) is a complicated clinical issue that requires an in-depth risk/benefit assessment. The term HRT includes both oestrogen plus progestin therapy (OPT) and oestrogen-only therapy (OT). Much research has been done with the former, but additional research is still needed for the latter. This chapter aims to provide a comprehensive overview of the key risks and benefits in order to assist clinicians and patients confronting this issue. In approaching the vast amount of data on HRT a caveat is in order: many of the issues involved are not black and white. The clinical data are often conflicting and careful analysis is required. Despite the discrepancies between the various HRT studies, there is much to be gleaned from a close examination of the data. The primary risks associated with HRT use are related to breast cancer and cardiovascular health. Recent clinical trial data have pointed to a slight increase in the number of breast cancers among women using HRT compared to placebo. With regard to cardiovascular health, the data have shown an increase in stroke and (VTE) but there is also evidence of a possible cardioprotective effect. The major benefits include relief of menopausal symptoms (including vasomotor instability, sexual dysfunction, mood, fatigue and skin issues) and a decrease in fracture risk.

Alzheimer Disease↗

Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study.

OBJECTIVE: To investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium. DESIGN: Clinical, placebo-controlled, randomized trial study.Healthy volunteers in an academic research environment. PATIENT(S): Fifty-five dancers (mean age: 22.0 +/- 4.6, age at menarche: 14.7 +/- 2.3 years), including 24 amenorrheics. INTERVENTION(S): Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day. MAIN OUTCOME MEASURE(S): Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine. Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization. CONCLUSION(S): These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea.

Adult↗

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.

Animals↗

Use of alternative therapies in menopause.

Hormone replacement therapy has traditionally been used to treat the accompanying symptoms of oestrogen deficiency in menopause. However, not all women can, or prefer to, receive this treatment and alternatives should be considered to reduce the increased risk of osteoporosis and heart disease in menopausal women. This chapter reviews the current literature on the efficacy of phyto-oestrogens in preventing cardiovascular disease, various cancers and osteoporosis, as well as treating the vasomotor and other menopause-related symptoms. Select herbal therapies, as well as selective oestrogen receptor modulators, are also considered.

Cardiovascular Diseases↗

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.

Adult↗

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.

Adult↗