Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.ROR
Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS) in women with irregular menses, yet the relationship between androgens and ovarian dysfunction remains poorly understood in eumenorrheic women.
Objective
The objective of the study was to evaluate whether sporadic anovulation was associated with higher T and anti-müllerian hormone (AMH; marker of ovarian follicle count) concentrations in eumenorrheic women.
Design
This was a prospective cohort study from 2005 to 2007.
Setting
The study was conducted at the University of Buffalo in western New York state.
Participants
A total of 259 eumenorrheic women without a self-reported history of infertility, PCOS, or other endocrine disorder participated in the study.
Main Outcome Measures
Total T and AMH were measured five to eight times per cycle for one (n = 9) or two (n = 250) cycles per woman (n = 509 cycles) with timing of menstrual cycle phase assisted by fertility monitors. Anovulatory cycles were defined biochemically by progesterone and LH concentrations. Repeated-measures ANOVA was conducted on log-transformed data with adjustment for age.
Results
Compared with ovulatory cycles (n = 467), sporadic anovulatory cycles (n = 42) had marginally higher total and significantly higher free T [mean 23.7 ng/dL (95% confidence interval [CI] 21.4-26.3) vs 21.6 ng/dL (95% CI 20.9-22.3), P = .08, and 0.36 ng/dL (95% CI 0.33-0.40) vs 0.32 ng/dL (95% CI 0.31-0.33), P = .02, respectively] during menses and also throughout the luteal phase (P < .01 for all). Women with higher T had elevated AMH concentrations, increased reporting of a history of acne requiring medical treatment, but not increased hirsutism.
Conclusions
Mechanisms of androgen-related ovulatory dysfunction that characterize PCOS in women with menstrual disturbances may occur across a continuum of T concentrations, including in eumenorrheic women without clinical hyperandrogenism.
PMID 24606085 24606085 DOI 10.1210/jc.2013-3781 10.1210/jc.2013-3781
Cite this article
Sjaarda, L. A., Mumford, S. L., Kissell, K., Schliep, K. C., Hammoud, A. O., Perkins, N. J., Weck, J., Wactawski-Wende, J., & Schisterman, E. F. (2014). Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype?. The Journal of clinical endocrinology and metabolism, 99(6), 2208-2216. https://doi.org/10.1210/jc.2013-3781
Sjaarda LA, Mumford SL, Kissell K, Schliep KC, Hammoud AO, Perkins NJ, et al. Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype?. J Clin Endocrinol Metab. 2014;99(6):2208-2216. doi:10.1210/jc.2013-3781
Sjaarda, L. A., et al. "Increased androgen, anti-Müllerian hormone, and sporadic anovulation in healthy, eumenorrheic women: a mild PCOS-like phenotype?." The Journal of clinical endocrinology and metabolism, vol. 99, no. 6, 2014, pp. 2208-2216.
Although adequate luteal hormone production is essential for establishing pregnancy, luteal phase deficiency (LPD) is poorly characterized among eumenorrheic women. We assessed the prevalence and overlap of two established short luteal phase duration less than10 days (clinical LPD) and suboptimal luteal progesterone of 5 ng/mL or less (biochemical LPD) and their relationship with reproductive hormone concentrations.
Design, Setting, We conducted a prospective study in western New York (2005-2007) following 259 women, aged 18-44 years, for up to two menstrual cycles. Among ovulatory cycles with recorded cycle lengths (n = 463), there were 41 cycles (8.9%) with clinical LPD, 39 cycles (8.4%) with biochemical LPD, and 20 cycles (4.3%) meeting both criteria. Recurrent clinical and biochemical LPD was observed in eight (3.4%) and five (2.1%) women, respectively. Clinical and biochemical LPD were each associated with lower follicular estradiol (both P ≤ .001) and luteal estradiol (P = .03 and P = .02, respectively) after adjusting for age, race, and percentage body fat. Clinical, but not biochemical, LPD was associated with lower LH and FSH across all phases of the cycle (P ≤ .001). Clinical and biochemical LPD were evident among regularly menstruating women. Estradiol was lower in LPD cycles under either criterion, but LH and FSH were lower only in association with shortened luteal phase (ie, clinical LPD), indicating that clinical and biochemical LPD may reflect different underlying mechanisms. Identifying ovulation in combination with a well-timed luteal progesterone measurement may serve as a cost-effective and specific tool for LPD assessment by clinicians and researchers.
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects. Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS. The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs). Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85). Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin. PROSPERO CRD42021283275.
Reproductive EndocrinologyMenstrual Cycle
Open Access
Stress is known to be associated with adverse health outcomes. The COVID-19 pandemic and its associated lockdowns are examples of chronic stressors. Lockdown measures inadvertently caused significant psychological distress and became a powerful source of anxiety/stress, sleep disturbances, nutritional changes and weight gain. Stress is known to impact women's health specifically, through hypothalamic-pituitary-gonadal (HPG) axis dysfunction and resultant ovulatory dysfunction. Such dysfunction may manifest in menstrual irregularities and/or infertility due to hypothalamic hypogonadism. Here, we review the key physiological mediators of stress and associated ovulatory dysfunction. The kisspeptinergic system is comprised of sets of neurons located in the hypothalamus, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC). This system links nutrition, reproductive signals and stress. It plays a key role in the function of the HPG axis. During chronic stress, the kisspeptinergic system affects the HPG axis, GnRH pulsatility, and, therefore, ovulation. Leptin, insulin and corticotrophin-releasing hormone (CRH) are thought to be additional key modulators in the behavioral responses to chronic stress and may contribute to stress-related ovulatory dysfunction. This mini-review also summarizes and appraises the available evidence on the negative impact of chronic stress as a result of the COVID-19 pandemic lockdowns. It proposes physiological mechanisms to explain the observed effects on women's reproductive health and well-being. The review suggests areas for future research.