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Factors Related to Declining Luteal Function in Women during the Menopausal Transition

Department of Obstetrics, Gynecology, and Women’s Health (N.S.), Albert Einstein College of Medicine, Bronx, New York 10461; University of Massachusetts Medical Center (S.L.C.), Worcester, Massachusetts 01655; University of California at Davis/Kaiser (W.L.L., E.B.G.), Davis, California 95616; Rush University (J.L.L., L.P.), Rush-Presbyterian St. Luke’s Medical Center, Chicago, Illinois 60612; University of Pittsburgh (K.A.M.), Pittsburgh, Pennsylvania 15219; University of Michigan (D.M., J.F.R., M.F.S.), Ann Arbor, Michigan 48104; University of California at Los Angeles (G.A.G., S.G.K.), Los Angeles, California 90095; and University of Medicine and Dentistry of New Jersey (G.W.), New Jersey Medical School, Newark, New Jersey 07103

Address all correspondence and requests for reprints to: Nanette Santoro, M.D., Professor and Director, Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Women’s Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Mazer 316, Bronx, New York 10461. E-mail: glicktoro{at}aol.com.

Context: Reproductive hormones are incompletely characterized during the menopause transition (MT).

Hypothesis: Increased anovulation and decreased progesterone accompany progress through the MT.

Design: The Daily Hormone Study (DHS) of the Study of Women’s Health Across the Nation (SWAN) included 848 women aged 43–53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr.

Main Outcome Measures: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables.

Results: Ovulatory-appearing cycles declined from 80.9% at baseline to 64.7% by the third assessment (H3). Cycles presumed anovulatory and not ending with bleeding by 50 d (anovulatory/nonbleeding) increased from 8.4 to 24% by H3 and were associated with progress to early perimenopause [odds ratio (OR) = 2.66; confidence interval (CI) = 1.17–6.04] or late perimenopause (OR = 56.21; CI = 18.79–168.12; P < 0.0001), African-American ethnicity (OR = 1.91; CI = 1.06–3.43), and less than high school education (OR = 3.51; CI = 1.62–7.62). Anovulatory cycles ending with bleeding remained at about 10% from baseline to H3; compared with ovulatory cycles, they were associated with obesity (OR = 4.68; CI = 1.33–16.52) and more than high school education (OR = 2.12; CI = 1.22–3.69; P = 0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pregnanediol glucuronide decreased 6.6% for each year on study. Insulin sensitivity measures did not relate strongly to menstrual cycle hormones.

Conclusions: Anovulation without bleeding represents progression of the MT. A small but detectable decrease in luteal progesterone excretion occurs as women progress through the MT.