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This version published online on February 19, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-2165
A more recent version of this article appeared on May 1, 2008
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Submitted on September 25, 2007
Accepted on February 8, 2008

Factors related to declining luteal function in women during the menopausal transition

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, L Powell, M F Sowers, and G Weiss

Department of Obstetrics, Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY 10461, University of Massachusetts Medical Center, Worcester, MA 01655, University of California at Davis/Kaiser, Davis, CA 95616, Rush University, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612, University of Pittsburgh, Pittsburgh, PA 15219, University of Michigan, Ann Arbor, MI 48104, and University of California at Los Angeles, Los Angeles, CA 90095, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103-2757

* To whom correspondence should be addressed. 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 SWAN, the Study of Women's Health Across the Nation, including 848 women aged 43–53 at baseline who collected daily urine for one cycle or up to 50 days annually for three years.

Main Outcome Measures: LH, FSH, estrone conjugates (E1c) and pregnanediol glucuronide (Pdg). 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 days (Anovulatory/nonbleeding) increased from 8.4% to 24% by H3, and were associated with progress to early (OR=2.66 [1.17,6.04]) or late perimenopause (OR=56.21 [18.79,168.12]), p<0.0001), African-American ethnicity (OR=1.91 [1.06, 3.43]) and <high school education (OR=3.51 [1.62, 7.62]). Anovulatory cycles ending with bleeding remained at about 10% from baseline-H3; compared to ovulatory cycles, they were associated with obesity (OR=4.68 [1.33, 16.52] and >high school education (OR=2.12 [1.22, 3.69], p=0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pdg 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.


Key words: menstrual cycle • menopausal transition • LH • FSH • estrogen • progesterone







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