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Menopause Matters

Menopause Transition
Evidence of Three Distinct Stages

Nancy Fugate Woods, RN, PhD, FAAN; Ellen Sullivan Mitchell, PhD, ARNP

Menopause is the permanent cessation of menstruation. During the years before menopause, women experience a variety of changes in their menstrual cycles. Some may notice that their periods are lighter or heavier, others may notice fewer days of menstrual bleeding and days of spotting before and after periods, and still others may notice that their periods occur 1 or 2 days earlier or later than they had in the past.*

Few studies have examined the natural history of the menopause transition and the physiologic changes linked to changing menstrual patterns. Evidence of a distinct progression of menstrual cycle changes before menopause has been detailed in the Seattle Midlife Women's Health Study.² Three distinct menopause transition stages-based on menstrual cycle calendars and comparisons with past cycles-were identified:

• Early stage, defined as changes in menstrual flow amount, duration, and/or cycle length in the presence of regular menstrual cycles for one calendar year
• Middle stage, defined as at least one episode of menstrual cycle irregularity ( > 7-day difference between consecutive cycle lengths), with no skipping of periods during a calendar year; irregular cycles persist until late stage occurs
• Late stage, defined as at least one skipped period (ie, the usual cycle length is at least doubled) during a calendar year; skipping of periods persists until menopause occurs.

This study also showed that the menopause transition, rather than being a single event, consists of various developmental stages that are often associated with different hormone levels and clinical symptoms. For example, urinary follicle-stimulating hormone (FSH) levels obtained from women during the late menopause-transition stage or after menopause were significantly higher than those obtained in women in the early or middle stage of the menopause transition. Urinary estrone levels were higher in women in the early, middle, or late stage than in postmenopausal women. In addition, hot flashes were significantly more prevalent among women in the late stage than in women in the early or middle stage.³

For many women, menstrual cycle changes similar to those seen in the middle or late stage of the menopause transition may occur as early as 4 to 8 years before menopause.⁴ These changing menstrual cycle patterns are probably caused by a decrease in ovulation frequency, by alterations in ovarian hormone levels, and by variations in serum FSH and luteinizing hormone levels.

Previous studies have shown that during the menopause transition, midcycle circulating levels of estrogen may be normal or increased,⁵ whereas androgen levels may be normal or decreased.⁶ Despite the high estrogen levels, FSH levels are frequently not suppressed, which may lead to overproduction of estradiol and, hence, hyperestrogenemia. It has been hypothesized that elevated estradiol levels may lead to symptoms such as fluid retention, irritability, and mastalgia, whereas fluctuating estradiol levels are associated with hot flashes, and falling estradiol levels are associated with urogenital symptoms such as vaginal dryness.

Many clinicians rely on a combination of menstrual cycle changes, vasomotor symptoms, and elevated FSH levels to confirm that the menopause transition has begun. However, these indicators may not be accurate. Validation of menstrual cycle changes requires patient self-reports, which are frequently inaccurate or incomplete. Serum FSH levels are so variable during the menopause transition that a single measure is not meaningful.

The key to identifying the stages of the menopause transition is the accurate collection of data on menstrual cycle changes-that is, alterations in flow amount or duration, alterations in cycle length, cycle irregularities, and skipped periods. (It is not necessary to measure FSH levels or ascertain vasomotor-symptom status.) Questionnaires on menstrual cycle changes and menstrual calendars can help women to record this information. Clinicians' careful instructions and follow-up can help to ensure accuracy.

The ramifications of these stages on clinical practice are not yet clear. Thus, deciding whether a particular woman has started the menopause transition-especially if she is younger than 45-remains a challenge. To aid clinicians in this regard, researchers are undertaking further efforts to identify the hormonal profile, symptoms, menstrual bleeding patterns, and duration for each menopause-transition stage, along with development of a practical classification schema. As more information becomes available, clinical applications of these data will become more apparent.

*Irregular uterine bleeding during the menopause transition is a normal, natural phenomenon. It is sometimes difficult to distinguish from abnormal uterine bleeding, which is a more serious concern requiring further investigation. Clinicians are advised to read the March 2000 Menopause Matters column¹ for more information about identifying and evaluating uterine bleeding during the menopause transition.

References

1. Archer DR. Perimenopausal uterine bleeding: keys to evaluation. The Female Patient. 2000;25:50,55.
   
2. Mitchell ES, Woods NF, Mariella A. Three stages of the menopausal transition from the Seattle Midlife Women's Health Study: toward a more precise definition. Menopause. 2000;7:334-349.
   
3. Mitchell ES, Woods NF. In preparation.
   
4. McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Fertil Steril. 1992;59:1-5.
   
5. Santoro N, Brown JR, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81:1495-1501.
   
6. Rannevik G, Jeppsson S, Johnell O, et al. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density. Maturitas. 1995;21:103-113

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