Progesterone and ovulation across stages of the transition to menopause

Abstract

Objective-Detailed characterization of progesterone and ovulation across the menopausal transition provides insight into conception risk and mechanisms of reproductive aging.Design-Participants (N=108, aged 25-58 years) collected daily urine specimens for six month intervals in each of five consecutive years. Specimens were assayed for pregnanediol-glucuronide (PDG), LH, FSH and estrone-glucuronide (E1G). Reproductive stage was determined using cycle length variance. A hierarchical algorithm was used to identify ovulation. Linear mixed-effects models estimated: 1) the frequency and day of ovulation by age and stage; 2) differences in FSH, LH, and E1G levels between ovulatory (O) and anovulatory (AO) cycles; and 3) total PDG levels and PDG levels in ovulatory cycles by age and stage.Results-The probability of AO cycles increased across the perimenopause (p<.0001); reproductive stage was a stronger predictor than age of the probability of anovulation. Most cycles in late perimenopause were anovulatory (>60%), but one quarter of cycles longer than 60 days were ovulatory. Average day of ovulation was later in the late perimenopause (mean (SD) cycle day 27 (25)) compared to the premenopause. FSH and LH levels were higher, and E1G levels lower, in AO than O cycles (p<.0001 for each). Total PDG decreased in the late perimenopause, but 95 th percentile PDG in ovulatory cycles declined steadily across the transition.Conclusions-Exposure to the risk of conception in women experiencing cycles long enough to classify them as late perimenopausal is far from negligible. Reproductive stage is more informative than age about PDG levels and the likelihood of anovulation.

Endocrinology of the Menopause

“…7,39 Prior to the complete loss of ovarian follicles, consistently increased FSH levels drive follicle development and estrogen synthesis and secretion to levels that may be many times higher than ever seen in normal cycles. 65 In the year before the FMP, 60% to 70% of cycles are either anovulatory or have prolonged follicular phases 69,70 consistent with hormonal data indicating that a significant number of increases in estradiol are not followed by an LH surge and an increase in progesterone. Generation of a preovulatory surge requires a highly specific pattern of increasing estrogen levels over an adequate duration, 71,72 both of which are likely to be altered in the face of asynchronous FSH and ovarian function.…”

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

“…In this age group the incidence of anovulatory cycles increases and plasma progesterone levels are lower compared with younger women (24,25). At this age follicle-stimulating hormone levels increase due to diminished ovarian reserve and contribute to a transient increase in plasma estradiol levels (26), thus potentially stimulating PR expression in target tissues, but it is unclear how this process might be present within leiomyoma and not in myometrium beside it.…”

Reproductive aging patterns in primates reveal that humans are distinct

“…In theory, this limitation on reproductive lifespan would constrain reproduction for any mammal whose lifespan routinely exceeded the hypothetical maximum "shelf-life" of mammalian primary oocytes (but see ref. 24). These constraints may have kept reproductive lifespan constant over human evolutionary history even as somatic lifespan increased (see also ref.…”