Characterization of reproductive hormonal dynamics in the perimenopause.

Abstract

Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.

Assessing menstrual cycles with urinary hormone assays

“…The additional participant burden imposed by weekly blood sampling was believed to be beyond what the participants would tolerate. Second, previous investigators have reported similar relationships between urinary pregnanediol glucuronide and serum progesterone in older women compared with younger women in the age groups we have studied herein (31). These data imply that there are not large changes in serum-to-urine steroid hormones that would render the Kassam algorithm less valid in the sample we have studied.…”

“…Glycerol-preserved specimens were used for all assays, because this has been reported to permit measurement of LH and FSH over long storage intervals (20) and does not interfere with E1c or Pdg assay (29,31). Samples were all normalized for the amount of creatinine in each specimen and are expressed per milligram creatinine (36).…”

“…In the cycles of women who are in their 40s, follicular phase shortening is often observed, along with increased FSH levels, especially in the early follicular phase of the cycle (16,18,(31)(32). The presumption that progesterone production follows ovulation and that corpus luteum function is Fig.…”

“…Correction of the urinary hormone value with creatinine excretion reduces within women variations in hormone concentrations, which can be considerable (25). Preservation of urine with glycerol is required to maintain gonadotropin activity in some (31) but not all (35) assays.…”

Assistierte Reproduktion bei Frauen mit einer beginnenden Perimenopause

“…Die Konzentration für Inhibin-B steigt in der Follikelphase, während die für Inhibin-A in der Lutealphase ansteigt [17]. Mit zunehmendem reproduktionsbiologischem Alter wird der Anstieg für Inhibin-B und Inhibin-A geringer [18]. [29].…”