Pubertal Timing, Androgens, and Obesity Phenotypes in Women at Midlife
ABSTRACT Context: Individuals with metabolically healthy or benign obesity vs. unhealthy or at risk obesity have been distinguished; however, the predisposing factors for developing these phenotypes are poorly understood. Objective: Our objective was to examine pubertal timing marked by menarcheal age in relation to at-risk obese, benign obese, and healthy normal-weight phenotypes at midlife and to characterize the potential role of androgens, marked by the free androgen index (FAI), in accounting for any associations between menarcheal age and obesity phenotype. Design: The study was cross-sectional. Setting and Participants: Participants included a multiethnic community sample of 989 premenopausal women ages 25-45 yr (mean = 35.2 yr; sd = 5.5 yr). Main Outcome Measure: Membership in at-risk obese, benign obese, and healthy normal-weight groups was defined by body mass index and number of metabolic syndrome components. Results: With each 1-yr increase in menarcheal age, the probability of having the at-risk obese compared with the healthy normal-weight phenotype decreased by 22%. This association attenuated when FAI was covaried, suggesting androgen levels may account for this association. In addition, higher FAI was independently related to having the at-risk obese compared with the healthy normal-weight phenotype as well as having the at-risk compared with the benign obese phenotype (all P < 0.05). Conclusions: Younger menarcheal age is associated with having the metabolically unhealthy obesity phenotype compared with the healthy normal-weight phenotype at midlife. This relation may be driven by levels of bioavailable androgens, which were especially elevated among women with the at-risk obesity phenotype.
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ABSTRACT: To investigate whether genetic polymorphisms in the FSH pathway (FSHB-211 G→T and FSHR 2039 A→G) affect serum levels of FSH, antimüllerian hormone (AMH), and age at pubertal onset. FSH secretion and FSH signal transduction are enhanced in carriers of FSHB GG and FSHR AA, respectively. Furthermore, the combined genotype FSHB GG+FSHR AA is the most favorable for male gonadal function, but the effect of this genotype has never been evaluated in peripubertal females. AMH is a marker of ovarian function and is negatively correlated with FSH in prepubertal girls. Secondary analyses of a prospective cohort study. General community. We examined 78 healthy girls twice yearly for 6 years; the median age at baseline was 9.3 years. None. Hormone levels were measured by immunoassays, and DNA was isolated from blood and genotyped by restriction fragment length polymorphism of polymerase chain reaction-amplified regions. Carriers of FSHB GG+FSHR AA had higher FSH before pubertal onset (median 2.2 vs. 1.5 IU/L) and lower AMH (13.8 vs. 19.4 pmol/L) compared with carriers of other genotypes. In crude analysis, girls with FSHB GG+FSHR AA entered puberty earlier, 9.7 vs. 10.6 years. However, the difference was no longer statistically significant after including interval-, right-, and left-censored data in a probit analysis. The combined effect of FSHB GG+FSHR AA may potentiate the FSH pathway, which increases serum levels of FSH and reduces AMH. Common variations in genes regulating follicle growth may affect AMH levels independently of the number of resting primordial follicles.Fertility and sterility 07/2013; 100(4). DOI:10.1016/j.fertnstert.2013.06.026 · 4.59 Impact Factor
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ABSTRACT: Obesity in women is associated with serious reproductive sequelae. Given its prevalence among women of reproductive age, much recent attention has focused on the mechanisms by which obesity affects female reproductive function and fertility. This review summarizes the literature investigating the epidemiology and pathophysiology of obesity in women of reproductive age and proposes research strategies that may help inform approaches to improve reproductive function and outcomes among obese women.Nutrition Reviews 10/2013; 71(S1). DOI:10.1111/nure.12056 · 5.54 Impact Factor
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ABSTRACT: This scoping review synthesizes existing research on two major transitions in females' lives: puberty and perimenopause. These two periods of vast physiological change demarcate the beginning and the end of the reproductive life cycle and are associated with major neuroendocrine reorganization across two key systems, the hypothalamic-pituitary-gonadal (HPG) axis the hypothalamus-pituitary-adrenal (HPA) axis. Despite growing evidence suggesting that the timing and experience of puberty and perimenopause are related to various physical and mental health outcomes (e.g., mood disorders, metabolism, cardiovascular health, autoimmune conditions, and cancer), these two processes are rarely examined together. In this paper, we bridge these disparate literatures to highlight similarities, isolate inconsistencies, and identify important areas for future research in women's health. Copyright © 2015 Elsevier Ltd. All rights reserved.Social Science [?] Medicine 03/2015; 132:103-112. DOI:10.1016/j.socscimed.2015.03.031 · 2.56 Impact Factor