Fertility and sterility · 2023
Effects of pulsatile intravenous follicle-stimulating hormone treatment on ovarian function in women with obesity.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Luu Thanh Ha, Kuhn Katherine, Bradford Andrew P, Wempe Michael F, Wittenburg Luke, Johnson Rachel L, Carlson Nichole E, Kumar T Rajendra, Polotsky Alex J
Аннотация
OBJECTIVE: To establish conditions for effective hypothalamic suppression in women with normal and high body mass index (BMI) and test the hypothesis that intravenous (IV) administration of pulsatile recombinant follicle-stimulating hormone (rFSH) can overcome the clinically evident dysfunctional pituitary-ovarian axis in women with obesity.
DESIGN: Prospective interventional study.
SETTING: Academic medical center.
PATIENT(S): Twenty-seven normal-weight women and 27 women with obesity, who were eumenorrheic and aged 21-39 years.
INTERVENTION(S): Two-day frequent blood sampling study, in early follicular phase, before and after cetrorelix suppression of gonadotropins and exogenous pulsatile IV rFSH administration.
MAIN OUTCOME MEASURE(S): Serum inhibin B and estradiol (E2) levels (basal and rFSH stimulated).
RESULT(S): A modified gonadotropin-releasing hormone antagonism protocol effectively suppressed production of endogenous gonadotropins in women with normal and high BMIs, providing a model to address the functional role of FSH in the hypothalamic-pituitary-ovarian axis. The IV rFSH treatment resulted in equivalent serum levels and pharmacodynamics in normal-weight women and those with obesity. However, women with obesity exhibited reduced basal levels of inhibin B and E2 and a significantly decreased response to FSH stimulation. The BMI was inversely correlated with serum inhibin B and E2. In spite of this observed deficit in ovarian function, pulsatile IV rFSH treatment in women with obesity resulted in E2 and inhibin B levels comparable with those in normal-weight women, in the absence of exogenous FSH stimulation.
CONCLUSION(S): Despite normalization of FSH levels and pulsatility by exogenous IV administration, women with obesity demonstrate ovarian dysfunction with respect to E2 and inhibin B secretion. Pulsatile FSH can partially correct the relative hypogonadotropic hypogonadism of obesity, thereby providing a potential treatment strategy to mitigate some of the adverse effects of high BMI on fertility, assisted reproduction, and pregnancy outcomes.
CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT02478775.
DESIGN: Prospective interventional study.
SETTING: Academic medical center.
PATIENT(S): Twenty-seven normal-weight women and 27 women with obesity, who were eumenorrheic and aged 21-39 years.
INTERVENTION(S): Two-day frequent blood sampling study, in early follicular phase, before and after cetrorelix suppression of gonadotropins and exogenous pulsatile IV rFSH administration.
MAIN OUTCOME MEASURE(S): Serum inhibin B and estradiol (E2) levels (basal and rFSH stimulated).
RESULT(S): A modified gonadotropin-releasing hormone antagonism protocol effectively suppressed production of endogenous gonadotropins in women with normal and high BMIs, providing a model to address the functional role of FSH in the hypothalamic-pituitary-ovarian axis. The IV rFSH treatment resulted in equivalent serum levels and pharmacodynamics in normal-weight women and those with obesity. However, women with obesity exhibited reduced basal levels of inhibin B and E2 and a significantly decreased response to FSH stimulation. The BMI was inversely correlated with serum inhibin B and E2. In spite of this observed deficit in ovarian function, pulsatile IV rFSH treatment in women with obesity resulted in E2 and inhibin B levels comparable with those in normal-weight women, in the absence of exogenous FSH stimulation.
CONCLUSION(S): Despite normalization of FSH levels and pulsatility by exogenous IV administration, women with obesity demonstrate ovarian dysfunction with respect to E2 and inhibin B secretion. Pulsatile FSH can partially correct the relative hypogonadotropic hypogonadism of obesity, thereby providing a potential treatment strategy to mitigate some of the adverse effects of high BMI on fertility, assisted reproduction, and pregnancy outcomes.
CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT02478775.