Amenorrheic Women Research Articles

Thinness and Time to Pregnancy among Rural Bangladeshi Adolescents

Few studies have examined the relationship between maternal nutritional status and fecundability. We assessed the temporal association between preconceptional mid‐upper arm circumference (MUAC), measured in adolescence (12–19 years) with low MUAC reflecting thinness, and time to pregnancy (TTP) among rural, newlywed, largely non‐contracepting (< 10.5%) women (n 5374) in northwestern Bangladesh. Women were recruited into a pregnancy surveillance system from 2001–2002 to participate in an antenatal vitamin A or beta‐carotene supplementation trial (West et al. JAMA 2011) and visited at home every 5 wks to ascertain a 1‐month history of menstruation. Amenorrheic women received a urine test to confirm pregnancy. Surveillance continued until pregnancy or for up to 312 weeks. Mean ± SD age and MUAC at surveillance enrollment were 15.3 ± 1.9 y and 22.5 ± 1.9 cm. Age at pregnancy ascertainment was 16.8 ± 1.9 y. Compared to those with a MUAC > 21.5 cm, adolescents with a smaller MUAC (≤ 21.5 cm) had a longer TTP (10 wks in median survival time, overall P < 0.001) and 5% lower cumulative incidence of first pregnancy (P < 0.001), evident at each age, but especially so among youngest newlyweds (12 to 13 y). In a Cox proportional hazards model, thinner women (MUAC < 21.5 cm) were 12% less likely to become pregnant than those better nourished, adjusting for age, year and season of enrollment, and family planning practice (HR 0.88, 95% CI 0.82–0.93, P < 0.001). Undernourished adolescent girls may experience a longer time to pregnancy than those of better nutritional status.Support or Funding InformationSupported by the Bill and Melinda Gates Foundation (GH614) and USAID, Washington DC.

Menses resumption after cancer treatment–induced amenorrhea occurs early or not at all

To identify factors associated with cancer treatment-induced amenorrhea and time to return of menses. Population-based cohort study. Not applicable. Female cancer survivors who were diagnosed with cancer between the ages of 20 and 35 and were at least 2 years postdiagnosis at the time of recruitment (median = 7 years; interquartile range, 5-11). None. Amenorrhea (≥6 months without menses) and resumption of menses. After excluding women with hysterectomies before cancer diagnosis, 1,043 women were eligible for analysis. Amenorrhea occurred in 31.6% of women. Among women treated with chemotherapy (n = 596), older age at diagnosis (30-35 vs. 20-24 years: adjusted odds ratio [aOR] = 2.37; 95% confidence interval [CI], 1.30, 4.30) and nulligravidity (vs. gravid: aOR = 1.50; 95% CI, 1.02, 2.21) were risk factors for amenorrhea. Among amenorrheic women, menses resumed in most (70.0%), and resumption occurred within 2 years of treatment for 90.0% of women. Survivors of breast cancer were more likely to resume menses at times greater than 1 year compared with lymphoma and pelvic-area cancers. Women diagnosed at older ages, those exposed to chemotherapy, and those exposed to any radiation experienced longer times to return of menses. Women who were older at diagnosis were more likely to have irregular cycles when menses returned. Treatment-induced amenorrhea is common in cancer survivors, although most women resume menses within 2 years. However, once resumed, older women are more likely to have irregular cycles. Age at diagnosis and pregnancy history affect the risk of amenorrhea.

Subclinical atherosclerotic risk in endurance-trained premenopausal amenorrheic women

PurposeIn premenopausal women, amenorrhea contributes to endothelial dysfunction. It is unknown whether this vascular functional change is associated with vascular structural change. MethodsThis study examined regional and systemic vascular structure and function to gain insight into subclinical atherosclerotic risk in 10 amenorrheic athletes, 18 eumenorrheic athletes, and 15 recreationally active controls. Brachial flow-mediated dilation (FMD) and low flow mediated constriction (L-FMC) were used to measure global endothelial function. Carotid-femoral pulse wave velocity (PWV) was used to measure aortic stiffness. Doppler-ultrasound of the superficial femoral artery (SFA) was used to assess intima-media thickness (IMT) and vessel diameter as indicators of vascular remodeling. ResultsAmenorrheic athletes had significantly lower brachial FMD adjusted for shear stimulus (6.9 ± 1.3%) compared with eumenorrheic athletes (11.0 ± 1.0%) and controls (11.0 ± 1.1%, p = 0.05). Brachial L-FMC (−1.8 ± 4.3%) and aortic PWV (5.0 ± 1.0 m/s) of amenorrheic athletes were similar to those of eumenorrheic athletes (L-FMC, −1.6 ± 4.6%; PWV, 4.6 ± 0.5 m/s) and controls (L-FMC, −1.5 ± 2.8%, p = 0.98; PWV, 5.4 ± 0.7 m/s, p = 0.15). SFA diameters were similar in amenorrheic athletes (5.7 ± 0.7 mm) and eumenorrheic athletes (5.7 ± 0.7 mm), but amenorrheic athletes had larger SFA diameters compared with controls (5.1 ± 0.6 mm, p = 0.04). In amenorrheic athletes, SFA IMT (0.31 ± 0.03 mm) was similar to that of eumenorrheic athletes (0.35 ± 0.07 mm) but significantly thinner compared to that of controls (0.38 ± 0.06, p = 0.01). ConclusionVascular dysfunction in female amenorrheic athletes is not systemic. Parenthetically, amenorrhea may not prevent favorable peripheral vascular structural adaptations to habitual exercise training.

Lactational amenorrhoea method for family planning.

It is estimated that about 40% of pregnancies in the world are unintended and that the major part of these are unwanted. There are several reasons no or ineffective contraception is used to prevent these pregnancies, including difficulty in obtaining contraceptives. The lactational amenorrhoea method (LAM) is a contraceptive method where the mother is informed and supported in how to use breastfeeding for contraception. LAM is available and accessible to many women. To assess the effectiveness of LAM, as defined in the 1988 Bellagio Consensus statement, as a contraceptive method in fully breastfeeding women, who remain amenorrheic, using pregnancy and menstruation life tables. We searched MEDLINE, EMBASE, POPLINE, and LILACS to 10 October 2014; reference lists of studies; review articles; books related to LAM; published abstracts from breastfeeding, reproductive health conferences; e-mails with study coordinators. Out of 459 potentially relevant studies, 159 investigated the risk of pregnancy during LAM or lactational amenorrhoea. Our inclusion criteria were as follows: prospective study; cases (intervention group) and, if available, controls, had to be sexually active; pregnancy had to be confirmed by physical examination or a pregnancy test. Our endpoints were life table menstruation rates and life table pregnancy rates. We included 15 studies reporting on 11 intervention groups and three control groups. We identified one additional uncontrolled study in the 2007 update and one additional controlled study in this 2015 update. Two review authors independently extracted data, resolving disagreements through discussion. We analysed the studies using narrative methods because of their heterogeneity. For the primary outcome, pregnancy, two controlled studies of LAM users reported life table pregnancy rates at six months of 0.45% and 2.45%, one controlled study reported 5% pregnancies in the absence of life table rates per month, and eight uncontrolled studies of LAM users reported pregnancy rates of 0% to 7.5%. Life table pregnancy rates for fully breastfeeding women who were amenorrheic but not using any contraceptive method were 0.88% in one study and 0.9% to 1.2% (95% confidence interval 0.0 to 2.4) in a second study, depending on the definition of menstruation used. The life table menstruation rate at six months in all studies varied between 11.1% and 39.4%. We found no clear differences in life table pregnancy rates between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. As the length of lactation amenorrhoea in women using LAM differed greatly between the populations studied, and was population specific, it is uncertain whether LAM extends lactational amenorrhoea.

Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea

Background: Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. Objective: To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. Design: This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Setting: Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. Results: BDNF plasma levels are significantly lower in amenorrheic women (p < 0.001) than in the follicular phase of eumenorrheic women. There are no correlations between BDNF values (p > 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Conclusions: Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA.

Menstrual restoration in severe panhypopituitarism many years after cranial irradiation for suprasellar germinoma

We report a very rare case showing menstrual restoration in severe pan-hypopituitarism many years after cranial irradiation for suprasellar germinoma. A 30-year-old, almost primarily amenorrheic woman with severe panhypopituitarism presented with cyclic genital bleeding for the previous five months. She had menstruated once, when she was 13 years old. When she was 14 years old, she was diagnosed with a suprasellar germinoma measuring 10 mm in diameter, which led to diabetes insipidus. Cranial irradiation with a total dose of 24 Gy and chemotherapy resulted in complete tumor remission. She developed severe hypopituitarism [luteinizing hormone (LH) = 0.4 mIU/mL, follicle-stimulating hormone (FSH) = 1.7 mIU/mL, and serum estradiol (E2) level < 10 pg/mL]. She had received multiple hormone replacement therapies for many years. When she was 29 years old, she expressed a desire to become pregnant. Serum gonadotropin and E2 levels increased (LH = 5.8 mIU/mL, FSH = 5.9 mIU/mL, and E2 = 58 pg/mL). She conceived with clomiphene therapy, and then delivered a healthy baby. Eight months after parturition, her basal body temperature and serum progesterone levels indicated recovery of ovulatory cycles. Ten months after parturition, she also spontaneously conceived. Menstrual restoration is very rare in severe panhypopituitarism after cranial irradiation. A relatively low dose of irradiation and small tumor size may have contributed to the recovery of menstruation in our patient.

Determinants of Unmet Need for Family Planning among Women in Rural Kenya

This paper aimed at identifying factors that contribute to unmet need for family planning among women in rural Kenya. Logistic regression analysis was carried out on 2008/09 Kenya demographic and health survey women-file data that left out currently pregnant and amenorrheic women. Among the variables found to be significantly related to unmet need for spacing, limiting childbearing and total unmet need were: marital status, current age, level of education, number of living children, employment status, region, household wealth index and exposure to mass media communications. In order to reduce unmet need for family planning in rural areas of Kenya, region-specific programmatic family planning action should be adopted; the government should prioritize female education and economic empowerment to women in rural areas; agencies involved in family planning provision and communication in rural Kenya should offer suitable services that target specific age groups, and with a greater focus on married women.

Traditional birthspacing practices and uptake of family planning during the postpartum period in Ouagadougou: qualitative results.

In many low-income countries, postpartum women typically start contraception after the resumption of sexual intercourse or menstruation. Postpartum breast-feeding and abstinence delay these events. Information is needed on women's motivations to rely on these traditional birthspacing practices and their difficulties in starting a contraceptive method after a birth in urban West Africa. In 2012, provider-client interactions and service delivery were observed for a week in seven health facilities in Ouagadougou, Burkina Faso, and semistructured interviews were conducted with 33 women and 12 men with infants younger than 24 months. Existing postpartum family planning services and women's transition from traditional practices to a family planning method are described. Family planning is scheduled to be delivered at the six-week postpartum checkup, which women rarely attend. No women viewed amenorrhea as protective against pregnancy, and all had started or planned to start a method just before or when they resumed sexual activity. Half of the women abstained for six or more months, and some then either adopted a method they used incorrectly or did not adopt one at all. The main difficulties included providers' requirements for amenorrheic women seeking contraceptives and husbands' refusal to refrain from unprotected sex. The initial postpartum family planning visit should occur right after delivery. Integration of family planning into immunization programs would provide opportunities to reach women who did not adopt a method early in the postpartum period. Provider barriers for amenorrheic women should be ended. Men should be involved in the postpartum family planning consultation.

Different bleeding patterns with the use of levonorgestrel intrauterine system: are they associated with changes in uterine artery blood flow?

Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates.

Effect of&amp;lt;i&amp;gt; Mentha longifolia&amp;lt;/i&amp;gt; on FSH Serum Level in Premature Ovarian Failure

Purpose: Premature ovarian failure (POF) includes cessation of normal ovarian function before age 40, causing amenorrhea, menopausal symptoms and general health problems. Hormone replacement therapy (HRT) can be administered in order to prevent menopausal symptoms, osteoporosis and vascular complications. Due to the contraindications and side effects of HRT and the increasing demand for alternative therapeutic modalities, we used Mentha longifolia, which is known in the Iranian traditional medicine (ITM), as being able to cause menstrual bleeding in women with early amenorrhea and decreased FSH serum. Methods: In this pilot study, we report twenty seven amenorrheic women with POF who were referred to the Iranian traditional medicine clinic in Tehran and treated by Mentha longifolia. All those patients had high FSH levels and amenorrhea. They were in their fertility age, between 30 to 40 years old. They were asked to take a cup of herbal tea which was steeped with Mentha longifolia tea three times a day for 2 weeks in 3 menstural cycles. If the patients developed menstruation, the FSH serum level was measured immediately; otherwise they had an FSH measurement one month after the beginning of therapy. Results: Mean age of patients was 36.44 ± 1.5 years. Mean FSH level before treatment was 79.13 ± 19.17 mIU/ml, and after treatment was 27.83 ± 16.14 mIU/ml. In four patients who did not have any response, mean range of FSH was 82.37 ± 19.75 mIU/ml before treatment and afterwards it was 81.97 ± 21.52 mIU/ml. After treatment with herbal teas, there was a significant decrease in FSH (79.39 ± 19.17 to 27.83 ± 16.14 mIU/ml, p value

The effect of ovarian dysfunction on bone mineral density in breast cancer patients 10 years after adjuvant chemotherapy

Background. Premenopausal patients treated with adjuvant chemotherapy often develop early menopause and thus, may encounter significant bone loss. We studied the long-term effects of chemotherapy-induced ovarian dysfunction on bone mineral density in breast cancer patients. Material and methods. The effect of menstrual status after adjuvant chemotherapy on bone mineral density (BMD) was examined in 29 premenopausal breast cancer patients. Results. During 10 years of follow-up, nearly 90% of women developed menstrual irregularities or amenorrhea. The total bone loss at the lumbar spine was −5.4% in women with preserved menstruation, −15.3% in those with irregular menses and −13.2% in amenorrheic women 10 years after adjuvant chemotherapy. The changes in lumbar spine BMD correlated significantly with menstrual function. Both amenorrhea and menstrual irregularities shortly after chemotherapy increased the risk of osteoporosis later on: one third of women with ovarian dysfunction developed osteoporosis of the lumbar spine during the follow-up. Osteopenia before adjuvant therapy predicted an increased risk for osteoporosis. Conclusion. The present study with a unique follow-up period of 10 years shows that ovarian dysfunction leads to long-term deleterious BMD changes and predisposes breast cancer survivors to osteoporosis.

Body composition and reproductive function exert unique influences on indices of bone health in exercising women

Reproductive function, metabolic hormones, and lean mass have been observed to influence bone metabolism and bone mass. It is unclear, however, if reproductive, metabolic and body composition factors play unique roles in the clinical measures of areal bone mineral density (aBMD) and bone geometry in exercising women. This study compares lumbar spine bone mineral apparent density (BMAD) and estimates of femoral neck cross-sectional moment of inertia (CSMI) and cross-sectional area (CSA) between exercising ovulatory (Ov) and amenorrheic (Amen) women. It also explores the respective roles of reproductive function, metabolic status, and body composition on aBMD, lumbar spine BMAD and femoral neck CSMI and CSA, which are surrogate measures of bone strength. Among exercising women aged 18–30years, body composition, aBMD, and estimates of femoral neck CSMI and CSA were assessed by dual-energy x-ray absorptiometry. Lumbar spine BMAD was calculated from bone mineral content and area. Estrone-1-glucuronide (E1G) and pregnanediol glucuronide were measured in daily urine samples collected for one cycle or monitoring period. Fasting blood samples were collected for measurement of leptin and total triiodothyronine. Ov (n=37) and Amen (n=45) women aged 22.3±0.5years did not differ in body mass, body mass index, and lean mass; however, Ov women had significantly higher percent body fat than Amen women. Lumbar spine aBMD and BMAD were significantly lower in Amen women compared to Ov women (p<0.001); however, femoral neck CSA and CSMI were not different between groups. E1G cycle mean and age of menarche were the strongest predictors of lumbar spine aBMD and BMAD, together explaining 25.5% and 22.7% of the variance, respectively. Lean mass was the strongest predictor of total hip and femoral neck aBMD as well as femoral neck CSMI and CSA, explaining 8.5–34.8% of the variance. Upon consideration of several potential osteogenic stimuli, reproductive function appears to play a key role in bone mass at a site composed of primarily trabecular bone. However, lean mass is one of the most influential predictors of bone mass and bone geometry at weight-bearing sites, such as the hip.

Factors affecting unmet need for family planning in Eastern Sudan

BackgroundIn the developing countries millions of women in the reproductive age who don’t use contraceptives prefer to postpone or limit their birth. This indicates their failure to take necessary decision to prevent and avoid unwanted pregnancy.MethodsA community-based cross sectional household survey was conducted to investigate unmet need for family planning and associated factors and total demand for family planning in Kassala, Eastern Sudan between 1st May and 31st July 2012.ResultsA total of 812 married women were enrolled in this study. Their mean age and parity was 31.8 (7.3) and 3.4 (1.8) respectively. Ever use of contraception was 25.4% (206/812) and 26.2% (213/812) were currently using contraception. Unmet need for spacing was 15.1% while unmet need for limiting was 0.7%. The pregnant and amenorrheic women whose the pregnancy or birth was unwanted and mistimed were 105 (13%) and 130 (16%) respectively. Using Westoff model the total unmet need was estimated as 44.8%. The total demand for family planning was 71%.In logistic regression model, while age, age at marriage, parity, residence and experience of child death were not associated with total unmet need for family planning, women education < secondary level (OR=7.8; CI=5.6-10.9; P=0.00), husband education < secondary level (OR=1.9; CI=1.3-2.6, P = 0.00) and woman’s occupation; housewife (OR=4.3; CI=2.5-7.2; P=0.00) were associated with the total unmet need.ConclusionsUnmet need for family planning in Eastern Sudan was significantly higher among women with less than secondary education. Also; it is influenced by couple’s educational status and woman’s occupation. The results of this study necessitate the need for the programme managers to take into account the concept of reproductive health education.

Analysis of Factors Involved in Lactational Amenorrhea

Although most studies show that breastfeeding delays the resumption of ovarian cyclicity and menses, Lactational Amenorrhea (LA) is its highly variable among different populations. Research has shown differences hormonal levels between fully nursing amenorrheic women and who those who recovered menses during the first six postpartum months: E2 levels or PRL/E2 ratio could be predictive of this condition. However, research about this phenomenon is not conclusive. Thus, this review article, through an analysis of secondary, summarizes the main factors involved in LA, considering its importance as a effective and natural contraception method.

Metformin for Antipsychotic-Induced Adverse Effects in Women with Schizophrenia

Metformin has been used successfully to treat polycystic ovary syndrome (PCOS), restore menstruation in amenorrheic obese women, and improve

Comparison of Hormonal and Metabolic Characteristics and Ovary Response to Induced Ovulation in Amenorrheic and Oligomenorrheic Women with PCOS

Objective To compare differences in endocrine and metabolic characteristics and response to induced ovulation treatment between oligomenorrheic and amenorrheic women with polycystic ovary syndrome (PCOS). Methods A total of 154 infertile PCOS patients presenting with oligomenorrhea or amenorrhea were retrospectively analysed, the differences in endocrine and metabolic characteristics and induced ovulation outcome parameters between oligomenorrheic and amenorrheic women were compared. Results Total follicle count, serum levels of total testosterone (TT), luteotropic hormone (LH) and insulin resistant index (HOMA-IR) were significantly higher in amenorrheic patients compared with oligomenorrheic patients (P Conclusions The degree of cycle irregularity might be a simple and effective clinical parameter to estimate the degree of metabolic and endocrine disorders and response to induced ovulation.

86 RELATIONSHIP BETWEEN MUSCLE QUALITY AND OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN: A PILOT STUDY

Objective: To determine the response to the progestin challenge test on endometrial thickness 40 UI/ml and Estradiol <20 pg. There was a positive correlation with estradiol on ultrasound endometrium thickness. Conclusion: Measured endometrial thickness appears to be a better assay of endometrial estrogen response than estradiol levels as good as progestin withdrawal bleeding. The progestin challenge test in amenorrheic women is a good method for judging the severity of ovarian dysfuntion.

Further evidence that FSH causes bone loss independently of low estrogen

IntroductionThe premise that menopause causes osteoporosis was firstproposed by Fuller Albright at the Massachusetts GeneralHospital [1]. His hypothesis linking the loss of sex steroidsto bone loss led to estrogen hormone replacement therapy(HRT) becoming the first successful treatment for osteo-porosis [2]. More recently, however, a finer re-examinationof menopausal bone loss has revealed that nearly half oflifetime loss occurs within the first 5 years [3, 4]. Bone lossaccelerates dramatically during the late peri-menopause,and can, in fact, be most rapid up to 3 years before the lastmenstrual period [3–5] (Fig. 1a). During this early phaseup to 5 years before the last menstrual period, estrogenlevels are relatively unperturbed, whereas follicle-stimu-lating hormone (FSH) levels are rising to compensate forfailing ovaries [6, 7] (Fig. 1b). These most rapid rates ofbone loss cannot conceivably be explained by low estro-gen; other pathophysiological mechanisms must play adominant role.In the early 2000s, we showed that pituitary hormonescan directly affect the skeleton by bypassing their usualendocrine targets. Thyroid-stimulating hormone (TSH) wasfirst documented to regulate bone remodeling directly byacting on both osteoclasts and osteoblasts [8]. Not only didthis study attribute the osteoporosis of hyperthyroidism, inpart, to low TSH levels, it set forth a new paradigm for theexistence of a pituitary-bone axis (Fig. 2). As part of thisparadigm shift, we later discovered that FSH directlystimulates bone resorption [9]; thus the idea that rising FSHlevels during the late peri-menopause could potentiallycontribute to the bone loss traditionally attributed solely tolow estrogen [10]. We are by no means limiting the provenimportance of low estrogen in causing bone loss. Instead,we suggest circumstances, such as the late peri-menopause,where FSH may play a dominant role.Several studies have confirmed direct effects of FSH onbone. Amenorrheic women with a higher mean serum FSH(*35 IU/L) have greater bone loss than those with lowerlevels (*8 IU/L) in the face of near-equal estrogen levels[11]. Likewise, in a recent study, patients with functionalhypothalamic amenorrhea, in whom both FSH and estrogenwere low, showed slight to moderate skeletal defects [12].Furthermore, women harboring an activating FSH receptor(FSHR) polymorphism, rs6166, have lower bone mass andhigher resorption markers [13]; this attests to a role forFSHRs in human physiology, and perhaps, even humanpathophysiology. Consistent with these human studies,exogenously administration of FSH to rats augmentedovariectomy-induced bone loss [14, 15]. Moreover, an FSHantagonist reduced bone loss post-ovariectomy, as well asthat induced by exogenous FSH [14, 15].Clinical correlations between bone loss and serum FSHlevels have been documented extensively. Most impressiveis the Study of Women’s Health across the Nations(SWAN), a longitudinal cohort of 2,375 peri-menopausalwomen. Not only was there a strong correlation betweenserum FSH levels and markers of bone resorption, a changein FSH levels over 4 years predicted decrements in bone

Is the Pill the Answer for Patients with the Female Athlete Triad?

As a family and sports physician, I care for many young women affected by the female athlete triad. Typically, they present with low body mass index (BMI), oligomenorrhea or amenorrhea, and, oftentimes, low bone mineral density or stress fractures. Sometimes, the low BMI stems from intentional restriction of dietary intake; other times, it is a consequence of an unintentional mismatch of caloric intake relative to high calorie expenditure related to training and/ or sport participation. Menstrual dysfunction may take the form of delayed menarche, short infrequent menses (oligomenorrhea), or complete absence of menstruation (amenorrhea). In this setting, bone health alterations are thought to be related to changes in one’s hormonal milieu, in addition to nutritional deficiencies. The mainstay of clinical management for patients affected by the female athlete triad is to correct the negative energy balance or low energy availability that leads to menstrual dysfunction and alterations in bone health. However, as many clinicians know, this can be challenging. Competitive female athletes often are resistant to recommendations to increase dietary intake and body weight and/or reduce their exercise or training. A common practice has been to place amenorrheic women, especially athletes, on oral contraceptives (OCP) in an effort to provide estrogen replacement, in hopes of protecting against bone loss and/or stress fracture. However, there is emerging evidence that this practice is not beneficial and may even lead to harm. The amenorrhea that occurs within the spectrum of the female athlete triad is referred to as functional hypothalamic amenorrhea. It is an adaptive mechanism that reduces a woman’s fertility when the body perceives that there is inadequate energy to support the substrate, let alone a fetus (2). While this may seem beneficial to many athletes, as they may not be seeking pregnancy, the adverse effects of this hormonal disruption is manifest in negative impacts on bone health, 1) in the form of inadequate bone mineral acquisition, 2) in the loss of existing bone mineral density, or 3) in increased risk of stress fracture, even in the setting of normal BMD. Combined OCP, consisting of estrogen and progesterone, have been recommended for use in treating women affected by the female athlete triad (1). However, the evidence supporting a role for OCP in treatment is inconclusive at best (5). This likely is related to the fact that combined OCP containing only estrogen and progesterone cannot overcome the alterations in hormone levels associated with low energy availability, including decreased total triiodothyronine, leptin, insulin, insulin-like growth factors, glucose, luteinizing hormone pulsatility, and follicle-stimulating hormone, as well as an increase in growth hormone and cortisol (5). Not only are OCP unable to counter the impact these hormone alterations have on bone health; they may contribute, in fact, to worsening bone health. Exogenous estrogen replacement in young athletes may lead to premature closure of physes (growth plate) (4), and early OCP use has been associated with lower BMD in the spine and femoral neck among female distance runners (6). So what is a clinician to do when faced with the challenge of treating an athlete with the female athlete triad? The first step is to perform a comprehensive history and physical examination to confirm the diagnoses. Second, engage a multidisciplinary team, which often includes a physician, sports dietician, and mental health professional, to guide and support the athlete’s recovery. The cornerstone of treatment is to reverse the situation of low energy availability, which is typically a consequence of both inadequate stored energy (low BMI) and low energy intake relative to expenditure. The goal is to increase caloric intake above 30-kcalIkg fat-free mass (FFM); some would recommend upward of 45-kcalIkg FFM to produce changes in bone mineral density (3,7). What this translates into practically is approximately 1,912 cal for a 110-lb female distance runner with 15% body fat (110 lb 0.85 = 93.5-lb FFM Y 42.5-kg FFM 45-kcalIkg FFM = 1,912 kcal). Assuming she was continuing to train throughout this recovery period, adding additional calories to cover exercise-related expenditures would be required to replace the deficit (~100 kcalImile). The role of the sports dietician is to help the athlete consume the required amount of calories while minimizing INVITED COMMENTARY

Turner Syndrome: Contemporary Thoughts and Reproductive Issues

Turner syndrome is a common genetic disorder that has been classically associated with a 45,X karyotype. Several X-chromosomal abnormalities have been identified in these patients, many of which involve mosaicism. These patients have variable but predictable phenotypic findings and are at risk for development of endocrine, autoimmune, and structural abnormalities. As many as 1.5% of the population with Turner syndrome may develop dissection and rupture of the ascending aorta; the presence of abnormalities of the cardiac tree and hypertension increase this risk, but their absence does not preclude it. Rupture has occurred at aortic diameters smaller than previously reported for other patient populations. Five percent or more of women with Turner syndrome may have abbreviated menstrual function before developing amenorrhea and hypergonadotropic hypogonadism. An estimated 1 to 2% of all patients may become pregnant. Only three patients with Turner syndrome (and two of them with streak ovaries) have ever been reported to become pregnant after developing amenorrhea and elevated gonadotropin levels. Pregnancy, either spontaneous or more commonly from donor oocyte, increases maternal mortality rate for these women by an estimated ≥100 fold. It appears that all Turner women are at risk of rupture; neither prior spontaneous menses nor age >30 years provides protection. In addition, the literature suggests that the physiological changes of pregnancy may increase the risk of rupture in future years after delivery for those Turner women who seemingly made it safely through pregnancy. The use of the term PRIMARY OVARIAN INSUFFICIENCY (POI) for Turner syndrome gives me some discomfort. For women with 46,XX hypergonadotropic hypogonadism, POI accurately provides the suggestion that follicular depletion is often not complete (although remissions are usually self-limiting and the vast majority of patients will not spontaneously become pregnant). I clearly understand the need to prevent any stigmatization to patients unfortunately diagnosed with premature oocyte depletion, and I believe that the use of the diagnosis POI leaves the door open for the occurrence of reproductive function and for the 5 to 10% of 46,XX patients who may spontaneously become pregnant. However, the world literature reports only two women with Turner syndrome, hypergonadotropic amenorrhea, and streak ovaries who have ever become pregnant spontaneously after their diagnosis. It would be unfair to such women with Turner syndrome to give them the same hope for pregnancy as we do for women with 46,XX POI. Amenorrheic women with Turner syndrome truly have ovarian failure. Although I have adopted the term POI in this article for women with Turner syndrome, semantics are no substitute for honest, thorough, and compassionate counseling.