Ovulation disturbances and perimenopause

The following will briefly describe the perimenopausal prevalence and incidence of ovulation disturbances while expanding on a previous review (Prior 1998). Cross-sectional data will be reviewed before the prospective and epidemiological data are examined.

The earliest cross-sectional studies of ovulation in 40—50 year old women used non-quantitative basal temperature methods. Collett et al (1954) documented 302 cycles from 146 women aged 17—50 using the basal temperature nadir (assessed visually from graphed data) as the day of ovulation. By these imperfect temperature analysis criteria, 15.1% of cycles in women ages 40—50 were anovulatory. This contrasted with an average of about 2% anovulatory cycles in women aged 25—34. Doring (1969), also using non-quantitative basal temperature methods, showed SLP and anovulatory cycles were more prevalent in cyclic women of increasing age.

Vollman, a Swiss physician, collected basal temperatures for 14 848 cycles in over 500 women and analysed them using an innovative quantitative mean basal temperature (QBT) analysis method (that has subsequently been validated against the midcycle LH peak; Prior et al 1990b). Women were stratified by gynaecological age (years since menarche); the prevalence of ovulation disturbances was documented to be almost 60% in the first year and about 21% in the cycles at highest gynaecological ages (Vollman 1977) (Fig. 3). Results from the three large basal temperature-based data sets differ from those of the majority of smaller cross-sectional studies using hormonal measurements. Four careful studies did not show lower progesterone or PdG levels in older women (Lee et al 1988, Reame et al 1996, Reyes et al 1977, Welt et al 1999). However, two hormone-based cross-sectional studies did show significantly lower progesterone levels or PdG excretions in older women (Ballinger et al 1987, Santoro et al 1996). One study tested PdG from daily overnight urine samples across one cycle in women with regular cycles, contrasting 11 women over age 47 with 11 under 36. The older women had significantly lower PdG levels as well as higher urinary total oestrogen excretions (Santoro et al 1996). Similar results were obtained using weekly serum sampling (Ballinger et al 1987).

Thus cross-sectional studies suggest but do not support the hypothesis that ovulation disturbances are more prevalent in perimenopause. However, in none

TABLE 1 Proposed phases of the perimenopause: clinical and hormonal characteristics

Phase A Phase B Phase C Phase D Phase E

Duration Menstrual cycles

Flow

Menstrual cycle-related symptoms

Regular — cycle length shorter; short FP+. Usually ovulatory

Increased or the same

| breast tenderness, mood swings and swelling before flow*. Dysmenorrhoea +1 Headaches | and/or migraines start

Regular — cycle length shortest; short FP+. Onset of ovulatory disturbances — short luteal phase and anovulation

Often increased in duration and amount

Irregular—alternating short and long cycles, normal ovulation less than 50%

ft with flooding or J,; often alternating breast tenderness, Less cyclic breast, mood swings and mood and fluid swelling before symptoms*, or flow*. present and

Often unpredictable.

ff dysmenorrhoea. Dysmenorrhoea less Headaches in migraine related to flow. May sufferers often severe occur at midcycle or for many days in the cycle

Oligomenorrhoea. Rare normal ovulatory cycles

1 year

Amenorrhoea

Spotting alternating None with flooding is common

Breast tenderness persistent in some women + other premenstrual symptoms*

Breast tenderness, mood and fluid symptoms less*. Sometimes occur without subsequent

Dysmenorrhoea may be flow.

J, or persistent in a Dysmenorrhoea few. Sometimes is usually gone relieved with flow

Vasomotor symptoms

Hormonal characteristics

Often begin. First onset, cyclic before and during flow usually in the night or very early morning hours. May occur at midcycle. Rare daytime VMS | E2 in early FP and premenstrually. FSH normal

LH normal ? Inhibin B J, Inhibin A normal

Cyclic related to flow Night sweats still tend Night and day VMS Night and day VMS

and usually still night sweats during or at the end of sleep. Fewer VMS in midcycle Rare daytime VMS

11 E2 especially with ovulatory disturbances.

FSH intermittently

LH normal.

Inhibin B l

Inhibin A J, with ovulatory disturbances to be cyclic, but less predictable. For some women VMS symptoms J, but others begin to have marked

First daytime VMS

E2 normal alternating with especially around flow no longer predict flow. For some women they may be very severe both day and night, especially in long cycles may become daily and incessant. In others they are rare, have decreased or generally disappear

| FSH more common.

E2 normal except || levels intermittently in long cycles. |FSH

E2 normal or slightly low but intermittently.

Inhibins B and A both below assay sensitivity

|, moderately increased; ||, very high; ?, uncertain; E2, oestradiol; +FP, follicular phase; , premenstrual symptoms; VMS, vasomotor symptoms. Modified from Prior (1998).

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