Body composition characteristics, sex hormone levels and circadian gonadotropin fluctuations in infertile young women

The present study dealt with the interaction between body composition estimated by means of dual energy x-ray absorptiometry, sex-specific fat distribution and sex hormone levels (LH, FSH, estradiol, prolactin, DHEA-S, androstendione, testosterone and SHBG) as well as LH and FSH fluctuations in infertile young women ageing between 18 and 30 years (x = 23.4 yr). Twenty patients suffered from polycystic ovaries (PCO), 15 women suffering from a mild anorexia nervosa were amenorrhoeic for more than one year. Marked associations between estradiol, testosterone, SHBG as well as the FSH output and body fat, bone mass and fat distribution were documented. PCO patients exhibited a high weight status and a typical android fat distribution which signals infertility comparable to postmenopausal women. In contrast, although anorexia patients had pathological decreased estrogen levels and were infertile at the time of investigation, their fat distribution was be classified as 'ypergynoid' and signals potential reproductive capability after a sufficient weight gain.     

Association between Serum Leptin Levels and 24‐Hour Blood Pressure in Obese Women

Objective: To assess the relationship between serum leptin and 24‐hour blood pressure (BP) in obese women, according to body fat distribution. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 70 nondiabetic, normotensive, obese women (40 with android and 30 with gynoid type of obesity) and 20 nonobese healthy women as a control group. All subjects underwent 24‐hour ambulatory BP monitoring. Blood samples were collected for serum leptin and plasma insulin measurements. Total cholesterol and high‐density lipoprotein cholesterol were also measured. Results: Serum leptin levels were significantly higher in obese subjects than in controls, and they were more elevated in android obese women than in gynoid ones. Leptin levels were positively related to body mass index (BMI), insulin, and waist and hip circumferences in the android group. Among gynoid subjects, leptin levels showed positive associations with BMI and insulin. In women with android obesity, strong positive correlations (p < 0.001) were found between leptin levels and 24‐hour systolic BP (SBP), daytime SBP, nighttime SBP, 24‐hour diastolic BP (DBP), and daytime DBP. Multiple regression analyses, including age, insulin and leptin concentrations, BMI, and waist and hip circumferences on 24‐hour and daytime SBP and DBP, showed that only leptin levels contributed to the variability of BP. Conclusions: Our study shows that serum leptin levels are directly related to 24‐hour BP levels in normotensive women with android fat distribution, independently of BMI.     

Anticardiolipin antibodies in women with unexplained infertility

Concept of autoimmune basis of infertility is still controversial, particularly regarding the presence of non-organ specific autoantibodies. Non-organ specific anticardiolipin (aCL) and antithyroglobulin (TgAt) antibodies were detected in infertile women. Both partners were evaluated according to the criteria of The American Society for Reproductive Medicine. All the results were normal in cases of unexplained infertility. Antisperm antibodies (ASA) were determined by a mixed antiglobulin reaction (MAR) and the Kibrick agglutination assay, aCL by commercial ELISA, TgAt by commercial RIA. Fertile women had children. Subjects were grouped in fertile (n=27), infertile (n=65), and cases of unexplained infertility (n=42). In fertile women, aCL was below the negative cut-off value (100 %), while women with unexplained infertility were positive in 23.8 %. Anticardiolipin (aCL) antibodies were detected in 21.5 % of infertile patients, most of them with unexplained infertility (15.4 %). Other positive women had partners with ASA (4.6 %), or exhibited a negative postcoital test (1.5 %). In this study aCL were not detected in women with ASA. TgAt incidence was increased in infertile (20 %) and unexplained infertility group (21.4 %) compared to the fertile controls (18.5 %). Increased incidence of aCL and TgAt in infertile women supports the contention that these autoantibodies contribute to the infertility     

Body shape and women’s attractiveness

This paper examines the role of body fat distribution as measured by waist-to-hip ratio (WHR) on the judgment of women’s physical attractiveness. It presents evidence that WHR is correlated with a woman’s reproductive endocrinological status and long-term health risk. Three studies were conducted to investigate whether humans have perceptual and cognitive mechanisms to utilize the WHR to infer attributes of women’s health, youthfulness, attractiveness, and reproductive capacity. College-age as well as older subjects of both sexes rank female figures with normal weight and low WHR as attractive and assign to them higher reproductive capability. The study concludes that WHR is a reliable and honest signal of a woman’s reproductive potential. The adaptive significance of body fat distribution and its role in mate selection is also discussed.     

Fat in android, trunk, and peripheral regions varies by ethnicity and race in college aged women

The aim of this study was to determine whether quantity of fat is different across the central (i.e., android, trunk) and peripheral (i.e., arm, leg, and gynoid) regions among young African-American (AA), Asian (AS), Hispanic (HI), and non-Hispanic white (NHW) women. A cohort of 1,161 women (18-30 years) from university physical activity classes were assessed for body composition via dual-emission X-ray absorptiometry (DXA). The mean total body fat percent (TBF%, x = 31.0 ± 7.36%, range = 11.4-54.4%) indicates sufficient variability for the aims. A linear mixed model (LMM) revealed an ethnicity by region fat% interaction (P < 0.0001). Differences existed between ethnicities for each region fat% (all P's < 0.0001) except between HI and AA for the arm region (P = 0.0086) and between AS and NHW for all peripheral regions (P > 0.05). AAs had the highest fat% and HI had the second highest fat% for each region. AS had the third highest fat% for the trunk and android regions. For each ethnicity, the gynoid region had the greatest fat%, followed by the android region, whereas the arm region had the lowest fat%. Future research needs to determine if ethnic differences in central body fat in young women are associated with health outcomes such as cardiovascular disease and insulin resistance.     

Ethnic and gender consensus for the effect of waist-to-hip ratio on judgment of women’s attractiveness

The western consensus is that obese women are considered attractive by Afro-Americans and by many societies from nonwestern developing countries. This belief rests mainly on results of nonstandardized surveys dealing only with body weight and size, ignoring body fat distribution. The anatomical distribution of female body fat as measured by the ratio of waist to hip circumference (WHR) is related to reproductive age, fertility, and risk for various major diseases and thus might play a role in judgment of attractiveness. Previous research (Singh 1993a, 1993b) has shown that in the United States Caucasian men and women judge female figures with feminine WHRs as attractive and healthy. To investigate whether young Indonesian and Afro-American men and women rate such figures similarly, female figures representing three body sizes (underweight, normal weight, and overweight) and four WHRs (two feminine and two masculine) were used. Results show that neither Indonesian nor Afro-American subjects judge overweight figures as attractive and healthy regardless of the size of WHR. They judged normal weight figures with feminine WHRs as most attractive, healthy, and youthful. The consensus on women’s attractiveness among Indonesian, Afro-American, and U.S. Caucasian male and female subjects suggests that various cultural groups have similar criteria for judging the ideal woman’s shape.     

Subcutaneous adipose tissue pattern in lean and obese women with polycystic ovary syndrome

The new optical device, Lipometer, permits the noninvasive, quick, safe, and precise measurement of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe the SAT topography (SAT-Top) like an individual "fingerprint." SAT-Top was examined in 33 women with polycystic ovary syndrome (PCOS), in 87 age-matched healthy controls and in 20 Type-II diabetic women. SAT-Top differences of these three groups were described, and, based on a hierarchical cluster analysis, two distinctly different groups of PCOS women, a lean (PCOS(L)) and an obese (PCOS(O)) cluster, were found. For visual comparison of the different types of body fat distribution, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. For comparison of the PCOS like body fat distribution with the "healthy" fat pattern, the (previously published) SAT-Top results of 590 healthy women and men (20-70 years old) and 162 healthy girls and boys (7-11 years old) were added to the factor plot. PCOS(O) women showed a SAT-Top pattern very similar to that of women with Type-II diabetes, even though the diabetic women were on average 30 years older. Compared with their healthy controls, SAT-Top of these PCOS(O) patients was strongly skewed into the android direction, providing significantly decreased leg SAT development and significantly higher upper body obesity. Compared with healthy women, PCOS(L) patients had significantly lower total SAT development (even though height, weight, and body mass index did not deviate significantly), showing a slightly lowered amount of body fat in the upper region and a highly significant leg SAT reduction. This type of fat pattern is the same as found in girls and boys before developing their sex specific body fat distribution. We conclude that women with PCOS develop an android SAT-Top, but compared in more detail, we found two typical types of body fat distribution: the "childlike" SAT pattern in lean PCOS patients, and the "diabetic" body fat distribution in obese PCOS women.     

Strategies to improve fertility of high yielding dairy farms: Management of the dry period

Reproductive performance of dairy cattle has been related to a wide variety of indicators of energy status, e.g., extent of negative energy balance, time of energy balance nadir, body weight loss, body condition score, and body condition score loss. Energy balance begins to decrease during the last few weeks prior to calving primarily due to a 30-35% reduction in feed intake. Cows typically remain in negative energy balance for five to seven weeks postpartum. Nutritional strategies to improve energy balance during the transition period include fat supplementation and feeding additional nonfiber carbohydrate. Unfortunately, neither approach is likely to markedly enhance energy status, although fat supplementation may increase reproductive efficiency independent of any effect on energy balance. Alternative management strategies may be required to improve fertility of dairy cows. Shortening or eliminating the dry period may improve energy status of dairy cows and increase reproductive efficiency. Shortening or eliminating the dry period may enhance dry matter intake during the transition period, decrease milk energy output, or both. A preliminary study using small animal numbers indicated that reducing dry period length to 28 or 0 days may decreases days to first ovulation, increase first service conception rate, and decrease days open. A follow-up study employing large animal numbers confirmed that reducing dry period length from 55 to 34 days can decrease days to first ovulation and decrease the percentage of anovular cows. The reduction in days open was greater for older cows than second parity cows. The reduction in days open was not related to effects of treatment on milk yield. Shortening or eliminating the dry period may be a more successful approach to improving reproductive efficiency than diet manipulation.     

Sex‐ and Depot‐Dependent Differences in Adipogenesis in Normal‐Weight Humans

To elucidate cellular mechanisms of sex‐related differences in fat distribution, we determined body fat distribution (dual‐energy X‐ray absorptiometry and single‐slice abdominal computed tomography (CT)), adipocyte size, adipocyte number, and proportion of early‐differentiated adipocytes (aP2⁺CD68^?) in the stromovascular fraction (SVF) in the upper and lower body of normal‐weight healthy men (n = 12) and premenopausal women (n = 20) (age: 18–49 years, BMI: 18–26 kg/m²). Women had more subcutaneous and less visceral fat than men. The proportion of early differentiated adipocytes in the subcutaneous adipose tissue SVF of women was greater than in men (P = 0.01), especially in the femoral depot, although in vitro adipogenesis, as assessed by peroxisome proliferator activated receptor‐γ (PPARγ) expression, was not increased in femoral preadipocytes cultured from women compared with men. In women, differentiation of femoral preadipocytes was less than that of abdominal subcutaneous preadipocytes (P = 0.04), and femoral subcutaneous preadipocytes tended to be more resistant to tumor necrosis factor‐α (TNFα)–induced apoptosis (P = 0.06). Thus, turnover and utilization of the preadipocyte pool may be reduced in lower vs. the upper‐body fat in women. Collectively, these data indicate that the microenvironment, rather than differences in inherent properties of preadipocytes between genders, may explain the gynoid obesity phenotype and higher percent body fat in women compared to men.     

Cross-cultural consensus for waist–hip ratio and women's attractiveness

In women of reproductive age, a gynoid body fat distribution as measured by the size of waist–hip ratio (WHR) is a reliable indicator of their sex hormone profile, greater success in pregnancy and less risk for major diseases. According to evolutionary mate selection theory, such indicators of health and fertility should be judged as attractive. Previous research has confirmed this prediction. In this current research, we use the same stimulus for diverse racial groups (Bakossiland, Cameroon, Africa; Komodo Island, Indonesia; Samoa; and New Zealand) to examine the universality of relationships between WHR and attractiveness. As WHR is positively correlated with body mass index (BMI), we controlled BMI by using photographs of women who have gone through micrograft surgery for cosmetic reasons. Results show that in each culture participants selected women with low WHR as attractive, regardless of increases or decreases in BMI. This cross-cultural consensus suggests that the link between WHR and female attractiveness is due to adaptation shaped by the selection process.     

Circadian phase difference of leptin in android versus gynoid obesity

A circadian rhythm in serum leptin, measured every 4 h for 24 h, characterizes normal-weight women (N = 14), and women with gynoid (N = 17) or android (N = 26) obesity, peaking around midnight (P < 0.05), but differing by about 3 h between android and gynoid women (P < 0.01). Obesity is associated with a higher MESOR (rhythm-adjusted mean; P < 0.001) and a smaller relative circadian amplitude (P < 0.05). Gynoid obesity is associated with a larger circadian amplitude of cortisol (P < 0.05), whereas android obesity is associated with a larger circadian amplitude and a higher MESOR of insulin (P < 0.05). Understanding putative mechanisms underlying different body fat distribution may lead to improved chronotherapeutic measures.     

Sex‐Specific Fat Distribution Is Not Linear Across Pubertal Groups in a Multiethnic Study

Objective: To investigate sexual dimorphism and race differences in fat distribution (android/gynoid) before and during puberty. Research Methods and Procedures: Fat distribution was measured by skinfold thickness and DXA in healthy African‐American, Asian, and white subjects (n = 920), divided into pre‐, early, and late pubertal groups. Results: Gynoid fat masses adjusted for covariates were lower in late pubertal compared with prepubertal boys, but were not consistently greater in late pubertal compared with prepubertal girls. Progression of sex‐specific fat distribution with increasing maturation was present in Asians only. Among African‐American and white subjects, early pubertal boys had greater gynoid fat mass compared with the prepubertal group, whereas early pubertal girls had less gynoid fat mass compared with the prepubertal group. Sexual dimorphism in fat distribution was present in all pubertal groups, except among whites at early puberty. Among girls, Asians had lower gynoid fat than whites and African Americans in all pubertal groups. Among boys, Asians had less gynoid fat by DXA in early puberty and late puberty. Discussion: Comparison among races demonstrated differences in sexual dimorphism and sex‐specific fat distribution with progression in pubertal group. However, in all race groups, the fat distribution of late pubertal boys was more “male” or “android” than prepubertal boys, but late pubertal girls did not differ consistently from prepubertal girls. These findings suggested that the greater sexual dimorphism of fat distribution in late puberty compared with prepuberty may be attributable to larger changes in boys with smaller changes in girls.     

Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people

Background

Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population.

Methods and Findings

As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm² and 126.9±55.2 cm² in men (P = 0.045) and 120.0±46.7 cm² and 211.8±65.9 cm² in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area.

Conclusions

Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution.     

Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women

The new optical device, the lipometer, enables the noninvasive, quick, safe, and precise determination of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe a SAT topography (SAT-Top) like an individual "fingerprint" of a subject. This SAT-Top was examined in 16 women with polycystic ovary syndrome (PCOS) and compared to the body fat distribution of 87 age-matched healthy controls and 20 type-2 diabetic women. SAT-Top differences of these three groups were described and, to render the possibility of visual comparison, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. All PCOS patients had an android body fat distribution with significantly thinner SAT layers on the legs as compared to healthy controls. Moreover, a hierarchical cluster analysis resulted in two distinctly different groups of PCOS women, a lean (PCOSL) and an obese (PCOSO) cluster: compared to healthy women, lean PCOS patients had significantly lower total SAT development, even though height, weight, and body mass index did not deviate significantly. Especially on the legs, their SAT layers were significantly lowered, indicating a more "apple-like" fat distribution type. Obese PCOS women showed a SAT-Top pattern very similar to that of women with type-2 diabetes, although the mean age difference between these groups was more than 30 years. Compared to healthy controls, the SAT-Top of these obese PCOS patients was strongly shifted into the android direction, appearing as "super-apples" with a significantly increased upper trunk obesity to 237.8% and a significantly decreased leg SAT development to 79.8%.     

Idiopathic infertility in married couples in the light of cytogenetic analysis and sperm penetration assay

We have selected 47 couples with unexplained infertility in order to analyse a possible link between sperm dysfunction studied in males in in vitro conditions and karyotype analysis of somatic cells. In order to identify so called "idiopathically infertile" couples we had to exclude any change in reproductive organs in both partners or in spermiogram which would qualify any of spouses into known category of infertility. We have revealed chromosome aberrations (translocations and marker chromosomes) in 19% of infertile males and in 6% of infertile females. Idiopathically infertile males had an overall decreased ability of sperm function (measured by proportion of penetrated hamster oocytes by human sperm) in comparison to fertile controls, however, still well placed within physiological range of values. Only sperm from a patient with identified translocation was clearly below the normal level of penetration (20% of penetrated oocytes), however, also the patients with revealed chromosome variant polymorphisms presented statistically lower values of penetration in comparison to fertile controls (39% vs 57%, p<0.05). On the contrary, patients with marker chromosomes did not exhibit affected sperm function. It can be speculated that only particular chromosome aberration in group of idiopathically infertile males may affect sperm functional capability (measured in vitro), however, the intragonadal genetic analysis has to be recommended in order to confirm such a causative link.     

Oral contraceptives and fat patterning in young adult women

90 nulliparous white female college students, selected from 2 undergraduate introductory courses at Kansas University, participated in a cross-sectional study designed to compare the fat distribution of oral contraceptive (OC) users to that of nonusers matched for height and weight. The subjects ranged in age from 18-26 years. The 30 OC users had been using the same brand of OCs for an average of 17.7 months (range of 3-36 months) and had not used another brand previously. Each OC user was matched to 2 nonusers. Each subject's height was measured to the nearest cm. A Detecto sliding-weight balance was used to measure body weights of the women (in light clothing) to the nearest 0.1 kg. Circumference measurements also were taken to determine body shape and fat distribution. The waist girth to hip ratio (WHR) also was calculated. Fat distribution of the OC users was similar to that of nonusers matched for height and weight. Both groups were comparable in their circumference and skinfold measurements, except that the OC users had larger axilla skinfolds. Progestational activity of the combined OCs was not associated with any of the physical measurements. Estrogenic activity of the combined OCs was correlated positively with body mass index, arm and thigh circumference, and peripheral fat distribution. Estrogenic activity also was associated weakly with hip and low chest circumferences but no with any of the 7 skinfold thickness measurements. The women taking the higher estrogen OCs were more likely to have circumference measurements consistent with a more gynoid shape. Thigh skinfold thickness was consistent with those findings, though not statistically significant.     

Associations of Platelet Indices with Body Fat Mass and Fat Distribution

Objective

This study was undertaken to investigate the associations of platelet indices with body fat, including body fat mass and fat distribution.

Methods

A total of 3,327 individuals aged 18 to 80 were enrolled. Body fat was assessed by dual‐energy x‐ray absorptiometry. Blood samples were collected to measure platelet indices (platelet count [PLT], plateletcrit [PCT], mean platelet volume, platelet distribution width, and platelet large cell ratio). Adjusted multivariate linear regression models were used to identify the associations of platelet indices with body fat.

Results

PLT was positively associated with BMI, waist circumference, waist‐hip ratio, total fat mass percentage, trunk fat mass percentage, android fat mass percentage, and android to gynoid fat ratio but negatively associated with gynoid fat mass percentage, total lean mass percentage, and skeletal muscle mass index. Similar associations were found between PCT and body fat. However, no significant associations were found between the other three platelet indices and body fat.

Conclusions

Both PLT and PCT were associated with body fat, and the associations depended on fat location. Because PCT is mainly influenced by PLT, these associations suggest that platelet quantity is more closely related to body fat mass and fat distribution.

     

Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise--a randomized controlled trial in overweight sedentary males

The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited. A randomized controlled trial was performed in healthy, sedentary, moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous sedentary control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high-exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ～30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH: -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P < 0.001) decreased similarly in both exercise groups. Although the exercise-induced energy expenditure in HIGH was twice that of MOD, the resulting accumulated energy balance, calculated from changes in body composition, was not different (MOD: -39.6 Mcal, HIGH: -34.3 Mcal, not significant). Energy balance was 83% more negative than expected in MOD, while it was 20% less negative than expected in HIGH. No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion, a similar body fat loss was obtained regardless of exercise dose. A moderate dose of exercise induced a markedly greater than expected negative energy balance, while a higher dose induced a small but quantifiable degree of compensation.     

Differences of subcutaneous adipose tissue topography in type-2 diabetic (NIDDM) women and healthy controls

Women suffering from type-2 diabetes mellitus (non-insulin-dependent diabetes mellitus [NIDDM]) have more total body fat and upper body obesity compared with healthy controls. However, the standard measurement methods have disadvantages such as radiological burden, lack of precision, or high time consumption. A new optical device, the Lipometer, enables the noninvasive, quick, and save determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 20 women with clinically proven NIDDM and 122 healthy controls matched by age group were measured. In this paper, we describe the precise SAT-Top differences of these two groups and present the multidimensional SAT-Top information condensed in a two-dimensional factor plot and in a response plot of an artificial neural network. NIDDM women provide significantly lower leg SAT-Top and significantly higher upper trunk SAT-Top development ("apple"-type) compared with their healthy controls.     

Physical work causes suppression of ovarian function in women.

The suppression of reproductive function is known to occur in women engaging in activities that require high energetic expenses, such as sport participation and subsistence work. It is still unclear, however, if reproductive suppression is a response to high levels of energy expenditure, or only to the resulting state of negative energy balance. To our knowledge, this study provides the first evidence that work-related energy expenditure alone, without associated negative energy balance, can lead to the suppression of reproductive function in women. We document suppression of ovarian function expressed as lowered salivary progesterone levels in women from an agricultural community who work hard, but remain in neutral energy balance. We propose two alternative evolutionary explanations (the ''pre-emptive ovarian suppression'' hypothesis and the ''constrained down-regulation'' hypothesis) for the observed results.