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The relationship between the endocrine characteristics and the regularity of menstrual cycles in the approach to menopause

Burger, Henry G MD1; Robertson, David M PhD1; Baksheev, Lyrissa BSc (Hons)1; Collins, Aila MD2; Csemiczky, Giorgy MD2; Landgren, Britt-Marie MD2

Articles

Objective: There is currently little longitudinal data available on the serum hormonal characteristics of the menstrual cycles observed in women as they approach their final menstrual period (FMP) or menopause. We sought to determine whether the onset of irregular menses, marking the menopause transition, signifies the occurrence of anovulatory, potentially infertile cycles.

Design: We studied 12 subjects, initially aged 45 to 47 years, who provided daily menstrual diaries, and had blood samples collected annually, three times weekly for 4 consecutive weeks, over a period of 36 to 98 months until FMP, for measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, and progesterone. The definition of entry into the early menopause transition was the occurrence of more than two cycles, in any consecutive sequence of 10, where cycle length was less than 23 or more than 35 days. Entry into the late transition was determined from the first observation of either 60-day or 90-day amenorrhea. Cycles were characterized endocrinologically as normal ovulatory, abnormal luteal phase, and anovulatory with evidence of ovarian follicular activity.

Results: The early transition had an average duration of 47 months from onset until FMP. Ten of the 12 subjects had one or more ovulatory cycles during the transition. Anovulatory cycles with ovarian activity were noted in 9 of the 12 subjects, only after entry into early and/or late transition.

Conclusions: Ovulatory cycles occurred both before and after entry into the early and/or late menopause transition in subjects older than 45 years of age, whereas anovulatory cycles were observed only during the transition. The ovulatory cycles were generally associated with normal menses, whereas anovulatory cycles showed long duration and/or abnormal bleeding patterns. The occurrence of cycle irregularity is associated with an increasing frequency of anovulatory cycles, which herald the occurrence of FMP. No conclusion could be drawn regarding the appropriate definition of entry into the late transition. The definition adopted for entry into the early transition merits further validation.

In an intensive 36- to 98-month longitudinal study of 12 normally menstruating women initially aged 45 to 47 years, ovulatory menstrual cycles were observed to continue after entry into the early and/or late menopause transition, whereas anovulatory cycles occurred only after menstrual irregularity began. Menstrual irregularity as women approach menopause does not necessarily signify the end of potential fertility.

From 1Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia; and 2Departments of Clinical Science, Obstetrics and Gynaecology, and Clinical Neurosiences, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.

Received May 24, 2004; revised and accepted July 27, 2004.

This study was financed by the Swedish National Banks Jubilee Foundation, by grants from the Karolinska Institute and The Swedish Medical Research Council (3972, 3529, 12238), and by a Program Grant (983212) from the National Health and Medical Research Council of Australia.

Address correspondence to: Prof. Henry G Burger, Prince Henry's Institute of Medical Research Monash Medical Center, Level 3, Block E 246, Clayton Road, Clayton, Victoria 3168, Australia. E-mail henry.burger@phimr.monash.edu.au.

©2005The North American Menopause Society