Progesterone and ovulation across stages of the transition to menopause.
OBJECTIVE
Detailed characterization of progesterone and ovulation across the menopausal transition provides insight into conception risk and mechanisms of reproductive aging.


METHODS
Participants (n = 108, aged 25-58 y) collected daily urine specimens for 6-month intervals in each of 5 consecutive years. Specimens were assayed for pregnanediol glucuronide (PDG), luteinizing hormone (LH), follicle-stimulating hormone (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 O cycles by age and stage.


RESULTS
The probability of AO cycles increased across the perimenopause (P < 0.0001); reproductive stage was a stronger predictor than age of the probability of anovulation. Most cycles in late perimenopause were AO (>60%), but one quarter of cycles longer than 60 days were O. Average day of ovulation was later in the late perimenopause (mean [SD] cycle day, 27 [25] d) compared with the premenopause. FSH and LH levels were higher and E1G levels were lower in AO than O cycles (P < 0.0001 for each). Total PDG decreased in the late perimenopause, but 95th percentile PDG in O 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.
O'Connor
Kathleen A
KA
Department of Anthropology, University of Washington, Seattle, WA 98195, USA. oconnork@u.washington.edu
Ferrell
Rebecca
R
Brindle
Eleanor
E
Trumble
Benjamin
B
Shofer
Jane
J
Holman
Darryl J
DJ
Weinstein
Maxine
M
D000328:Adult; D000375:Aging / Q000502:physiology; D000858:Anovulation; D015992:Body Mass Index; D004970:Estrone / Q000652:urine; D005260:Female; D005640:Follicle Stimulating Hormone / Q000652:urine; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000652:urine; D008593:Menopause / Q000502:physiology*; D008598:Menstruation; D008875:Middle Aged; D010060:Ovulation / Q000502:physiology*; D011276:Pregnanediol / Q000652:urine; D011374:Progesterone / Q000097:blood*; D055703:Reproductive Physiological Phenomena; D013997:Time Factors
D037101:Luteinizing Hormone, beta Subunit; D004970:Estrone; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D011276:Pregnanediol