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.

Patterns of LHbetacf among women in health and disease.

Urine based gonadotropin assays provide a practical means of analyzing hormone secretion patterns. While research protocols have revealed pulsatile patterns of gonadotropins such as LH in the blood, these assays are of limited clinical use since daily venipuncture sampling is not feasible outside of a research environment. However, collection of several urine samples provides a method to achieve the same visualization of gonadotropin patterns in patients using a convenient and generally applicable technique based on analysis of the highly stable hLHbetacf for monitoring LH and hCGbetacf for monitoring pituitary hCG. We demonstrated that two different sampling techniques for analyzing these gonadotropin metabolites yielded the same information on their excretory patterns, either sampling of spot urines or collecting first morning void urines for several days. Next, we studied the core excretory patterns in several populations: menstruating and postmenopausal women from the general population, and two populations of women from a fertility center, one of which had polycystic ovaries (PCO). The PCO population was also subdivided into those with and without insulin resistance (IR). It was found that our hLHbetacf assay did not measure the form of the LH core (v-hLHbetacf) produced in subjects who were homozygous for a variant form of LH (v-LH). None of our patients tested were homozygous for the variant form of LH. It was also found that in most non-PCO (NPCO) patients, the hLHbetacf peak lasted for 7-9 days while among the PCO patients this peak frequently lasted for less than 7 days and an erratic pattern tended to appear. The overall differences in patterns between the PCO and NPCO patients were confirmed by spectral statistical methods. The prevalence of certain characteristic hLHbetacf patterns may be higher among women with PCO with a more severe clinical presentation. Use of urinary analysis of gonadotropin metabolites, especially hLHbetacf, may supplement subjective ultrasound studies with more sensitive biochemical measurements.

Urinary beta-luteinizing hormone and beta-follicle stimulating hormone immunoenzymometric assays for population research.

OBJECTIVE: We developed assays for measurement of urinary betaLH and betaFSH under collection and storage conditions typical of non-clinical research settings. DESIGN AND METHODS: IEMAs for free betaLH and total betaFSH were validated by standard methods. Stability of urinary betaLH and betaFSH was tested across freeze-thaws and stored long term at 4 degrees C or -20 degrees C, or short term at room temperature, and with heating to dissociate the subunits. RESULTS: The IEMAs exhibited acceptable parallelism, specificity, recovery (averaging 100% for betaLH, 97% for betaFSH), imprecision (maximum within-run and between run CVs, respectively, 4.8% and 25.7% for betaLH, 5.6% and 17.0% for betaFSH), and minimum detectable dose (2.5 pmol/L for betaLH, 6.8 pmol/L for betaFSH). Urine and serum measures were highly correlated (r=0.95 for LH, 0.86 for FSH). There was no consistent decline with any storage type. Dissociation of subunits by heating was needed for betaLH, but not betaFSH. CONCLUSION: These IEMAs measure free betaLH and total betaFSH, overcoming inter-individual variability in, and collection and storage effects on, subunit dissociation, without the need for urine preservatives.