FRI420 Prevalence Of Ovarian Hormone Suppression Is High Among Regularly Cycling Reproductive-aged Women With Overweight Or Obesity
Authors: Caldwell Annie , Polotsky Alex J , Bradford Andrew P , Smyth Heather , Kuhn Katherine , Siegart Jamie , Santoro Nanette F , Catenacci Victoria A 
Published: October 2023

Disclosure: A. Caldwell: None. A.J. Polotsky: None. A.P. Bradford: None. H. Smyth: None. K. Kuhn: None. J. Siegart: None. N.F. Santoro: Advisory Board Member; Self; Astellas Pharma, Menogenix Inc., Que Oncology, Project Ember/Amazon. Grant Recipient; Self; Menogenix Inc. Other; Self; Ansh Labs Scientific Consultant. V.A. Catenacci: None.

Endo Abstract Background: The prevalence of ovarian hormone suppression in regularly cycling, pre-menopausal women with overweight or obesity (termed relative hypogonadotropic hypogonadism of obesity) is not fully appreciated, as there are no overt symptoms aside from subfertility in women trying to conceive. In addition to impacting fertility, ovarian hormones play an important role in energy homeostasis and fat distribution. Other states characterized by ovarian hormone suppression (polycystic ovarian syndrome, PCOS and menopause) are associated with increased cardiometabolic disease risk. It is therefore critical to have a better understanding of the prevalence of ovarian hormone suppression in women with overweight or obesity. Methods: We compared cycle length and ovarian hormones in pre-menopausal women (age 18-40) who had regular menstrual cycles, no history of PCOS or diabetes, and were not using hormonal birth control (currently or in the past 3 months) and were either with overweight or obesity (OW/O, BMI 27-40 kg/m2, n=23) or healthy weight (HW, BMI 18-25kg/m2, n=15). Both groups provided daily, first-morning voided urine samples over a complete menstrual cycle. Progesterone and estrogen metabolites were assayed (pregnanediol-3-glucuronide [Pdg], estrone-1 conjugates [E1c]; Centaur CP; Siemens) and adjusted for creatinine. Hormones were assessed using whole cycle area under the curve (AUC) measurement. Ovarian hormone suppression was defined a priori as Pdg AUC &lt; 25th percentile of the HW control group. T-tests and Spearman correlations were used to compare groups and examine associations between hormones and BMI. Mean±SD are presented. Results: Cycle length was not different between groups, but BMI (OW/O: 34.3±5.3, HW: 21.6±1.3 kg/m2) and age (OW/O: 34.6±5.3, HW: 29.2±4.2 years) were (p &lt; 0.01), thus all analyses controlled for age. Pdg was significantly lower (p&lt;0.01) in OW/O (AUC = 21.29±13.98 ug/mg Cr) relative to HW (AUC = 39.13±22.20 ug/mg Cr) and the majority (82.6%) of the OW/O women exhibited ovarian hormone suppression. E1c was also significantly lower (p&lt;.0001) in the OW/O (AUC = 384.8±211.4 ng/mg Cr) group relative to HW (AUC = 1740.00±627.20 ng/mg Cr). Across the full sample, there were negative correlations between BMI and Pdg AUC (rpartial = -0.34, p = .03) and BMI and E1c AUC (rpartial = -0.61, p &lt; .0001). Conclusion: Ovarian hormone suppression was observed in a majority of our sample of pre-menopausal women with overweight or obesity. Despite the difficulty of identifying this phenotype clinically, it may have important implications for weight management and cardiometabolic disease risk, in addition to fertility, and warrants further investigation to improve women’s health during the reproductive lifespan and beyond.

Presentation: Friday, June 16, 2023