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Pulsatile Luteinizing Hormone Amplitude and Progesterone Metabolite Excretion Are Reduced in Obese Women

Departments of Obstetrics, Gynecology, and Women’s Health (A.J., A.J.P., G.Z., S.F., B.I., N.S.) and Medicine (D.R., H.N.P.), Albert Einstein College of Medicine, Bronx, New York 10461; Department of Obstetrics and Gynecology (S.L.B., T.L.), Emory University, Atlanta, Georgia 30322; and Department of Surgery (K.G.), Montefiore Medical Center, Bronx, New York 10467

Address all correspondence and requests for reprints to: Nanette Santoro, M.D., Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Women’s Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461. E-mail: glicktoro{at}aol.com.

Context: Female obesity is linked to abnormal menstrual cycles, infertility, reproductive wastage, and deficient LH, FSH, and progesterone secretion.

Objective and Design: To elucidate the reproductive defects associated with obesity, we sampled 18 eumenorrheic (nonpolycystic ovary syndrome) women with a mean ± SEM body mass index of 48.6 ± 1.4 kg/m² with daily, first morning voided urine collections, seven of whom also had early follicular phase 12-h, every 10-min blood sampling to assess LH pulses. Daily hormones were compared with 11 eumenorrheic, normal-weight controls. A separate control group of 12 eumenorrheic, normal-weight women was used for the LH pulse studies.

Main Outcome Measures: Assays for LH (serum and urine) and FSH, and estradiol and progesterone metabolites (estrone conjugate and pregnanediol glucuronide; urine) were performed. Daily hormones were meaned and normalized to a 28-d cycle length. LH pulsations were determined using two objective methods. Group means were compared using t tests.

Results: Reduced whole-cycle mean, normalized pregnanediol glucuronide was observed in obese (38.2 ± 2.1 µg/mg creatine) compared with normal-weight women (181.3 ± 35.1 µg/mg creatine; P = 0.002), without significant differences in LH, FSH, or estrone conjugate. Early follicular phase LH pulse frequency did not differ from normal-weight women, but both amplitude and mean LH were dramatically reduced in obese women (0.8 ± 0.1 and 2.0 ± 0.3 IU/liter) compared with controls (1.6 ± 0.2 and 3.4 ± 0.2 IU/liter; P < 0.01).

Conclusions: A novel defect in the amplitude but not the frequency of LH pulsations appears to underlie the reproductive phenotype of obesity. The deficit in pregnanediol glucuronide appears to exceed the deficit in LH. The patterns of hypothalamic-pituitary-ovarian axis function unique to the obese state differ from other abnormal reproductive states.

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				N. Santoro, S. L. Crawford, W. L. Lasley, J. L. Luborsky, K. A. Matthews, D. McConnell, J. F. Randolph Jr., E. B. Gold, G. A. Greendale, S. G. Korenman, et al. Factors Related to Declining Luteal Function in Women during the Menopausal Transition J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1711 - 1721. [Abstract] [Full Text] [PDF]