Urine for the analysis of pregnanediol was collected weekly for 3 months from 209 menstruant women aged 11-24 years who lived with their parents and from 59 women aged 17-23 years who had left the parental home. Menstrual cycles were classed as ovulatory if the 24-h pregnanediol output in the 12 days preceding menstruation was greater than or equal to 5 mumol on a single occasion or if the total excreted on 2 days, 1 week apart, was greater than or equal to 7 mumol. In the first group, ovulatory incidence increased with menarchal age. Unfailing ovulation occurred in 22.9, 25.0, 44.8, 42.9, 63.2, 71.8 and 82.6% of those who were less than 1, 1- less than 2, 2- less than 3, 3- less than 4, 4- less than 5, 5-8 and 9-12 years from menarche. Comparable figures for the women who lived in flats and hostels were 40.0% (menarchal age, 5-8 years) and 78.6% (9-12 years). It is concluded that a regular pattern of ovulatory menstrual cycles is established in most young women within 5 years of the menarche, and that departure from the family home is often associated with a regression to a juvenile pattern of anovulatory menstrual cycles.

The excretion of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogens and pregnanediol was measured in weekly urine samples collected for 14-87 weeks (median, 43 weeks) from thirty-one perimenopausal women aged 36-55 years (median, 50 years). The results were compared with those found in twenty-two postmenopausal women aged 55.4 +/- 5.4 years (mean +/- SD), and in twenty premenopausal women aged 44.4 +/- 3.4 years with regular, ovulatory, menstrual cycles. Women classed as perimenopausal had a recent history of irregular menstrual cycles following regular cyclicity. The hormone patterns observed in the perimenopausal women varied widely, both between individuals and from time to time in the same individual. They ranged from ovulatory cycles with low premenopausal levels of FSH, to transient episodes indistinguishable from those found in postmenopausal women with high levels of FSH and LH. Between these extremes were patterns rarely seen at other times in reproductive life: namely, (1) in fourteen women on thirty-two occasions lasting 2-9 weeks, postmenopausal levels of FSH and LH occurred in association with high oestrogen levels; (2) in eighteen women on thirty occasions lasting 2-8 weeks, there was an elevation of LH (but not FSH) into the postmenopausal range; (3) in thirteen women on twenty-six occasions lasting 1-2 weeks, there was an elevation of FSH (but not LH) into the postmenopausal range. These patterns were not seen in any of the premenopausal women. Typically, the approach of the menopause was marked by an increased incidence of high postmenopausal levels of FSH and LH. Ovulatory cycles were observed at all stages in the perimenopause, and occurred within 16 weeks of the last menstrual period in seven of the thirteen women who became postmenopausal during the study. It is concluded that the appearance of high levels of FSH and LH is characteristic of the perimenopause and often precedes the sustained loss of sex hormone secretion by the ageing ovary. Postmenopausal biochemical parameters are no guarantee of the postmenopausal state.

In normal women the menopausal transition starts typically with a sudden break in regular menstrual cyclicity: gonadotrophin levels escape from the cyclical pattern characteristic of fertile women and increasingly rise into the postmenopausal range. An investigation was undertaken to determine whether this rise precedes the first appearance of ovarian dysfunction. Weekly urine samples for the measurement of FSH, LH and pregnanediol were collected from 100 women, all of whom had regular 20- to 35-day menstrual cycles (504 samples from 48 women aged 20-39 years and 620 samples from 52 women aged 40-48 years; 96.8% of these cycles were shown to be ovulatory). Excretion rates of FSH in excess of 5 i.u./24 h occurred more often in women aged greater than or equal to 40 years than in younger women (incidence, 31.5 cf. 19.5%; P less than 0.001). The difference was greatest at the time of the perimenstruum (7-day incidence, 32.5 cf. 13.9%) and declined to insignificance during the mid-cycle gonadotrophin surge (7-day incidence, 44.2 cf. 34.8%). Examination of the rank correlation between age and gonadotrophin excretion confirmed the age-related rise in FSH and identified a lesser but significant perimenstrual rise in LH. For both FSH and LH these changes were small compared with the increases observed in nine women presumed to have reached the menopausal transition during the trial (incidence FSH greater than or equal to 5 i.u./24 h, 60.6%; incidence LH greater than or equal to 5 i.u./24 h, 48.6%). It is concluded that in fertile women there is evidence of an age-related rise in FSH which is distinct from the changes occurring at the start of the menopausal transition.

SummaryUrine was collected at weekly intervals at weekly intervals for three or more months from 139 menstruant women aged 40–55 years. Menstrual cycles were classed as ovulatory if the 24-hr pregnanediol output was > 5 μmol on a single occasion, or if the total excreted on 2 days 1 week apart was > 7 μmol. Of the 81 women who reported no change in menstrual frequency, 95% ovulated in every cycle. Only 34% of the 53 with a recent history of oligomenorrhoea ovulated without fail. Ovalation occurred in 93% of all 21–35-day menstrual cycles, in 55% of 36–50-day cycles, in 40% of 51–75-day cycles and in 17% of those lasting > 76 days. Pregnanediol increases suggestive of ovulation and followed by menstruation were observed on 31 occasions after amenorrhoea of from 2 to 6 months' duration.

The excretion of FSH, LH, oestrogens and pregnanediol was monitored once weekly in urine samples collected from eight peri-menopausal women aged 44-55 years (median, 52 years). Observations were commenced between 5 and 15 weeks before the menopause and were continued for 22-30 weeks after final menstruation. Amenorrhoea of greater than 2 years duration in association with a persistent elevation in gonadotrophin output was considered proof of the post-menopausal state. No clear hormonal change occurred at the time of the menopause. During the peri-menopause there is a transition from the regular ovulatory cycles of pre-menopausal women to the unvarying high gonadotrophin and low oestrogen excretion which is generally regarded as being characteristic of post-menopausal women. In the group studied, post-menopausal levels of FSH and LH were common before and episodes of high oestrogen excretion were not uncommon after final menstruation. Menstrual failure appeared to occur spontaneously at some stage during the transition from the pre- to the post-menopausal state, and not to be associated with its conclusion. From the hormonal point of view the immediately post-menopausal period could not be distinguished from the long cycles of peri-menopausal women. This suggests that an endometrial rather than a hormonal event might determine the time at which menstruation stops during the menopausal transition.