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

Abstract

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.

Figure 1

Adjusted mean whole-cycle urinary reproductive hormones by cycle type. The indicated relationship and statistical significance level for each hormone are shown in the upper portion of each panel.

Figure 2

Mean daily patterns of FSH, LH, Pdg, and E1c in cycles without luteal function. •, Anovulatory cycles ending with a bleed; ○, anovulatory/nonbleeding collections. Anovulatory collections that did not end with a bleed were terminated at 50 d.

Figure 3

Adjusted mean whole-cycle urinary reproductive hormones (with CI) by age and elapsed years since baseline, ovulatory cycles only. The P value for each relationship is shown above the trio of bars to which it refers.

Figure 4

Adjusted mean whole-cycle urinary reproductive hormones (with CI) by ethnicity and metabolic syndrome, ovulatory cycles only. Asterisks above each pair of bars indicate statistical significance for metabolic syndrome-related differences. *, P < 0.05.

Figure 5

Adjusted OR for anovulation by baseline serum estradiol. The vertical line in the middle of the figure represents unity (OR = 1). The OR is shown as the middle of each horizontal line, with the outer limits representing the lower and upper CI.