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Estrogen priming may improve HPO axis function in women with obesity
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In ovulating women with obesity, estrogen priming appears to yield improvements in hypothalamic-pituitary-ovarian axis function and proinflammatory profiles, according to recent findings.
Alex J. Polotsky, MD, MS, of the University of Colorado School of Medicine, and colleagues evaluated 21 women with regular menstrual periods, 11 with obesity and 10 who were normal weight (controls), to determine the effects of estrogen priming on the hypothalamic-pituitary-ovarian (HPO) axis.
The main outcome measures were defined as blood luteinizing hormone and follicle-stimulating hormone (FSH) concentrations before and after gonadotropin-releasing hormone (GnRH) stimulation and urinary estrogen and progesterone metabolites.
The researchers found that after administration of transdermal estrogen, augmented luteinizing hormone pulse amplitude response to GnRH increased from 1.1 IU/L to 1.6 IU/L in the group with obesity, whereas there was a decrease from 2.7 IU/L to 2.2 IU/L in controls (P = .048).
After GnRH stimulation, estrogen priming at month 3 appeared to induce opposite changes in FSH response from month 1 in the controls vs. obesity group; controls demonstrated an average negative 24% change in mean FSH vs. 18% increase in the obesity group (P = .02).
After estrogen administration, oral progesterone was needed to stimulate menstruation in six controls and five participants with obesity because they did not have menstrual bleeding after 40 days of transdermal estrogen. After estrogen was primed at month 3, all controls and seven participants with obesity were ovulatory.
Baseline levels of the proinflammatory cytokines interleukin-6, IL-10, transforming growth factor-beta (TGF-b) and IL-12 were higher in the obesity group vs. controls (P < .05 for all). Retesting of these values at month 3 revealed a decrease in nine of 10 cytokines in the obesity group with decreases in IL-1b (–6%), IL-8 (–5%), TGF-b (–5%) and IL-12 (–5%) reaching statistical significance.
According to the researchers, these findings suggest that estrogen priming induces improved HPO axis function in conjunction with improved proinflammatory profiles in women with obesity.
“Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility,” the researchers wrote. “Given the public health implications of maternal obesity, future studies should address medical or nutritional strategies directed at decreasing chronic inflammation and alleviating the burden of obesity on reproductive fitness.” – by Jennifer Byrne
Disclosure: One of the researchers reports investigator-initiated grant funding from Bayer and stock options in Menogenix.
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