Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women
Richard W Browne, Torie Comeaux Plowden, Neil J Perkins
Rose G Radin, Lynne C Messer, Kara A Michels, Sunni L Mumford, Enrique F Schisterman, Karen C Schliep, Lindsey A Sjaarda, Jean Wactawski-Wende, Shvetha M Zarek, Jonathan Schmelzer
Author affiliations (5)
University at Buffalo, State University of New YorkROR
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentROR
Evidence is growing that the equilibrium between reactive oxygen species and antioxidants plays a vital role in women's reproductive health.
Objective
The objective of this study was to evaluate variations in serum antioxidant concentrations across the menstrual cycle and associations between antioxidants and reproductive hormones and anovulation among healthy women.
Methods
The BioCycle Study, a prospective cohort, followed 259 women aged 18-44 y for up to 2 menstrual cycles. Serum fat-soluble vitamin and micronutrient (α-tocopherol, γ-tocopherol, retinol, lutein, lycopene, and β-carotene), ascorbic acid, and reproductive hormone concentrations were measured 5-8 times/cycle. We used weighted linear mixed models to assess associations between antioxidants and hormone concentrations, after adjustment for age, race, body mass index, parity, sleep, pain medication use, total energy intake, concurrent hormones, serum cholesterol, F2-isoprostanes, and other antioxidants. Generalized linear models were used to identify associations with anovulation.
Results
Serum antioxidant concentrations varied across the menstrual cycle. Retinol and α-tocopherol were associated with higher estradiol [RR: 1.00 pg/mL (95% CI: 0.67, 1.34 pg/mL); RR: 0.02 pg/mL (95% CI: 0.003, 0.03 pg/mL), respectively] and testosterone [RR: 0.61 ng/dL (95% CI: 0.44, 0.78 ng/dL); RR: 0.01 ng/dL (95% CI: 0.001, 0.01 ng/dL), respectively]. Ascorbic acid was associated with higher progesterone (RR: 0.15 ng/mL; 95% CI: 0.05, 0.25 ng/mL) and with lower follicle-stimulating hormone (RR: -0.06 mIU/mL; 95% CI: -0.09, -0.03 mIU/mL). The ratio of αto γ-tocopherol was associated with an increased risk of anovulation (RR: 1.03; 95% CI: 1.01, 1.06).
Conclusions
These findings shed new light on the intricate associations between serum antioxidants and endogenous hormones in healthy premenopausal women and support the hypothesis that concentrations of serum vitamins affect steroidogenesis even after adjustment for oxidative stress.
serum antioxidants reproductive hormones, antioxidant menstrual cycle variation, oxidative stress ovulation, carotenoids reproductive hormones women, vitamin E estradiol progesterone, antioxidant anovulation risk, BioCycle Study antioxidants, reactive oxygen species reproductive health, selenium reproductive hormone association, antioxidant luteal phase function
PMID 26581679 26581679 DOI 10.3945/jn.115.217620 10.3945/jn.115.217620
Cite this article
Mumford, S. L., Browne, R. W., Schliep, K. C., Schmelzer, J., Plowden, T. C., Michels, K. A., Sjaarda, L. A., Zarek, S. M., Perkins, N. J., Messer, L. C., Radin, R. G., Wactawski-Wende, J., & Schisterman, E. F. (2016). Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women. The Journal of nutrition, 146(1), 98-106. https://doi.org/10.3945/jn.115.217620
Mumford SL, Browne RW, Schliep KC, Schmelzer J, Plowden TC, Michels KA, et al. Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women. J Nutr. 2016;146(1):98-106. doi:10.3945/jn.115.217620
Mumford, S. L., et al. "Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women." The Journal of nutrition, vol. 146, no. 1, 2016, pp. 98-106.
Attention-Deficit/Hyperactivity Disorder (ADHD) in girls and women is under-recognised and under-researched, despite increasing awareness of clinical challenges and unmet needs. This review by the Eunethydis Special Interest Group on Female ADHD, addresses current knowledge and identifies research gaps for future work. Issues in women with ADHD across the lifespan such as late diagnosis, pubertal development, sexual health, hormonal birth control, executive function difficulties, and gynaecological disorders associated with ADHD are highlighted. The review synthesises existing literature and self-reported experiences of women with ADHD to explore the impact of hormonal fluctuations [puberty, menstrual cycle, pregnancy, (peri)menopause] on ADHD symptoms and mood disturbances. It examines the interplay of oestrogen and progesterone with dopaminergic pathways, when periods of lower oestrogen may affect cognition, as well as the manifestation of executive function deficits, and the intersection of ADHD with reproductive health. Hormonal transitions exacerbate ADHD symptoms and mood disturbances, yet pharmacological research and tailored treatments are lacking. Executive function deficits manifest differently in girls and women with ADHD and are influenced by neuropsychological and neurobiological profiles. Diagnostic practices and sociocultural factors contribute to delayed diagnoses, increasing the risk of comorbidities, impaired functioning, and diminished quality of life. Undiagnosed women have increased vulnerability to premenstrual dysphoric disorder, postpartum depression, and cardiovascular disease during perimenopause. Longitudinal, sex-specific studies incorporating hormonal status and lived experience are needed. Individualised interventions should be developed to address the unique needs of girls and women with ADHD. Addressing these gaps will advance more equitable diagnosis, management, and support for girls and women with ADHD, improving outcomes across the female lifespan.
Insulin resistance and hyperinsulinaemia significantly influence female hormone regulation and reproductive health. Despite increasing research, the complex pathways by which nutritional and metabolic signals regulate reproductive function remain poorly understood. Sex hormone-binding globulin (SHBG) is a key protein whose function is modulated by hyperinsulinaemia, liver function, and metabolic status, thereby influencing the active signalling of circulating sex steroids and intracellular signalling, which in turn, impacts endocrine and reproductive physiology. Consequently, SHBG serves as a valuable biomarker for understanding the metabolic-hormonal interactions within the endocrine axis. Ketogenic diets have demonstrated efficacy in reversing insulin resistance, resolving markers of liver disease, and improving metabolic health. In this study, we investigated the impact of suppressing ketosis (hypoketonaemia) on biomarkers of female reproductive and endocrine function in the Ketosis Suppression and Ageing cohort. Ten lean (BMI, 20.52 kg/m2 ± 1.39), healthy, premenopausal women (mean age, 32.30 ± 8.97 years), who maintained nutritional ketosis for an average of 3.9 years (± 2.3), participated in a 21-days of baseline data-collection in euketonaemia, 21-days of hypoketonaemia, and 21-days return to euketonaemia. Suppression of ketosis resulted in a significant 0.67-fold decrease in SHBG levels (p = 0.0015). SHBG was significantly and inversely associated with insulin (p = 0.0010), insulin resistance score (HOMA-IR; p = 0.0012), glucose ketone index (GKI; p = 0.0183), leptin (p = 0.0016), insulin-like growth factor-1 (IGF-1; p = 0.0172), free T3 (p = 0.0001), and gamma-glutamyl transferase (GGT; p = 0.0024). A significant positive association between SHBG and GLP-1 (p = 0.0295) was observed. Menstrual cycle phase was a statistically significant predictor of follicle-stimulating hormone (FSH) levels, with higher FSH levels during ovulation than during the follicular phase (p = 0.0097). SHBG is a sensitive biomarker of metabolic-endocrine status, with broader implications for cancer, and reproductive function. Chronic hypoketonaemia negatively affects SHBG production and hormonal balance. The implications of sex-hormone regulation for cancer prevention and therapy are discussed.
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.