[ Editorials | Departments and Series | Index ]

Menopause Matters

The Perimenopausal Transition

Gerson Weiss, MD

In addition to raising the specter of aging, perimenopause is often fraught with uncertainty because of the fluctuations in hormone levels, menses, and menopausal symptoms. Given the difficulty of predicting menopausal timing, however, what can the clinician do?

Reproductive aging in women is a long process, ending in menopause. Initial aging changes begin in the midreproductive phase with a decreased ability to conceive. In most women, this change occurs in the mid-30s. Subsequently, there are slight elevations in follicle-stimulating hormone (FSH) throughout the menstrual cycle well before any alterations in cycle length.

back to top

DEFINITIONS

Perimenopause occurs later in this continuum. It begins with changes in the menstrual cycle—usually shortening, but also irregularity or lengthening. This is not a well defined point, and recognition largely depends on the woman’s awareness. Perimenopause ends at the onset of menopause, which is defined as 1 year after the final menstrual period (FMP).

Perimenopause is subdivided into early and late phases, with the late phase comprising the year after the FMP. Perimenopause has also been described as the period of greater irregularity and missed menses, with > 60 days of amenorrhea. However, many women do not fit into these definitions and continue to menstruate regularly until menses cease.

During perimenopause, roughly 20% of women will have anovulatory cycles interspersed with ovulatory cycles. Some anovulatory women have unresponsive ovaries, so that even with an estrogen peak followed by a normal surge of luteinizing hormone (LH), ovulation does not occur. Other women have an estrogen elevation sufficient to trigger an LH surge, but the surge does not occur and they do not ovulate. In a third scena-rio, the woman has a failure of negative feedback wherein the estrogen levels are adequate to suppress gonadotropin, but fail to suppress both LH and FSH.1 There is currently no way to predict these patterns, and they in turn cannot predict future hormone secretion or time to menopause. Nonetheless, because LH surges and high gonadotropin secretion can occur without ovulation, LH surge detection is a poor indicator of ovulation for women in this age group.

To address the need for better staging of female reproductive aging, the Stages of Reproductive Aging Workshop (STRAW) was held in Park City, Utah in July 2001. The product of this meeting was the STRAW staging system (Figure), which shows this process as a continuum from menarche through menopause and late postmenopause. The STRAW system focuses on phases rather than age or time periods because timing is extremely variable.2

Figure not available online

Stages of Reproductive Aging Workshop staging system. Adapted with permission from Soules MR, Sherman S, Parrott E, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril. 2001;76(5):874-878

back to top

HORMONAL AND CYCLE PATTERNS

Even with the STRAW system, however, some women do not fit the pattern. Women can sometimes regress in the menopausal progression, go directly from regular cycles to menopause, or have long periods of amenorrhea and then begin cycles again.3 In addition, ovulatory cycles in perimenopausal women may have different characteristics than cycles in younger women. Generally, the gonadotropin levels are higher than in younger women—especially FSH. Estrogen levels are generally comparable to or higher than those in younger women. Progesterone secretion in the older group has a lower peak and shorter duration.4 Overall, menses become longer and more infrequent as menopause approaches.

There is no certain way to predict when menopause will occur in any given woman. It is assumed that the higher the FSH level and the older the woman, the more likely it is that menopause is imminent. Generally, if the FSH level is > 40 mIU/mL during the early follicular phase (days 2 to 5), conception is extremely unlikely. This is when the FSH value is highest, except for the unpredictable midcycle FSH surge that accompanies the LH surge. Taffe and Dennerstein5 have shown that for women older than age 45 years, the time remaining to the FMP from the point at which the cycles are 42 days is related to both FSH levels and the woman's perception. The median number of months remaining ranged from 11 for those with FSH levels > 20 mIU/mL who felt they were in transition, to 21 months for those with lower FSH values who reported little evidence of transition. Another model for predicting age at menopause incorporates parity, body mass index (BMI), history of breast surgery, and presence of two gene polymorphisms.6 This formula may be too complicated for broad application, though. Bastian et al7 found that after considering age, the greatest positive predictors for the menopausal transition were self-assessment, hot flashes, night sweats, vaginal dryness, and high FSH and low inhibin levels; they expressly discouraged relying on laboratory results. Overall, FSH levels are not helpful in defining the exact stage of the transition or time to FMP.

back to top

FACTORS AFFECTING MENOPAUSE

The "normal" age of menopause is any time from 40 years or older. Multiple factors contribute to this wide variability. A report from the Framingham Heart Study8 suggests that at least 50% of individual variability is attributable to genetic causes. In addition, cigarette smoking has been shown to shorten the time to menopause by 1 to 3 years. There may be ethnic differences in hormone secretion; for example, Chinese American and Japanese American women have lower total cycle estrogen excretion than do white, black, or Hispanic women. Secretion of estradiol, dehydroepiandrosterone, sex hormone-binding globulin, and testosterone also vary by ethnicity and BMI.9 However, it is not clear what effect (if any) this has on age at FMP.

back to top

SYMPTOMS

Approximately 20% of perimenopausal women are symptom-free, whereas another 20% to 30% are significantly affected by symptoms. The remainder have manageable symptoms. The major symptom in the United States is vasomotor instability, which is more common in late perimenopause than after menopause. Other symptoms are more prominent in other countries. Some women experience symptoms throughout perimenopause, and others have them only in the late phase. In addition, breast fullness or enlargement is a frequent early to mid-perimenopausal symptom. Very obese women have an increased risk of hot flashes compared with normal-weight women,10 but weight loss can be difficult to achieve in this population.

Perimenopausal women may also experience a decline in sexual function.11 This may be due in part to the partnerÍs inability to perform, or disinterest. Past functioning and the strength of the relationship are more important factors in this setting than hormonal measurements.12

back to top

THERAPY

While there is a massive body of literature on hot flashes in postmenopausal women, few studies have focused on perimenopausal women. Hormone therapy would seem inappropriate in this group because estrogen is at normal or higher-than-normal levels. Moreover, the risks and benefits of estrogen use have not been clearly defined in this population. Cycles are frequently unpredictable in perimenopause, so that symptom patterns change. Many women fluctuate between later and earlier stages, and it is not unusual to have periods with intense symptoms interspersed with asymptomatic episodes. Hence, it is difficult to determine the efficacy of any therapy, as a positive affect could be due to either the therapy or to natural fluctuations in hormone levels.

Women who are troubled by menses that are irregular or too frequent can consider using low-dose oral contraceptives. Cyclic progesterone may be used as well to deal with anovulatory bleeding. Flow can be decreased with a progesterone-containing intrauterine device.

Control of weight, exercise, and smoking cessation can be helpful in the perimenopausal woman with periodic symptoms. Estrogen can be considered 1 year after the FMP. Psychological support is crucial, and the patient should be reassured that this is a phase and symptoms are transient.

back to top

CONCLUSION

Predicting the timing of menopause—or even confirming the FMP—remains maddeningly elusive. The problem is compounded by the variable and irregular nature of menses and symptoms in perimenopause, which also contributes to the patient's anxiety during this uncertain period. The clinician can do much to give reassurance, tracking the patient's symptoms and providing guidance throughout these transitional years.

back to top

Gerson Weiss, MD, is professor and chair, Department of Obstetrics and Gynecology and Women's Health, New Jersey Medical School, Newark.

References

1. Weiss G, Skurnick JH, Goldsmith LT, Santoro NF, Park SJ. Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA. 2004;292(24):2991-2996.
2. Soules MR, Sherman S, Parrott E, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril. 2001;76(5): 874-878.
3. Mansfield PK, Carey M, Anderson A, Barsom SH, Koch PB. Staging the menopausal transition: data from the TREMIN Research Program on WomenÍs Health. Womens Health Issues. 2004;14(6):220-226.
4. Santoro N, Lasley B, McConnell D, et al. Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of WomenÍs Health Across the Nation (SWAN) Daily Hormone Study. J Clin Endocrinol Metab. 2004;89(6):2622-2631.
5. Taffe J, Dennerstein L. Time to the final menstrual period. Fertil Steril. 2002;78(2):397-403.
6. Hefler LA, Grimm C, Bentz EK, Reinthaller A, Heinze G, Tempfer CB. A model for predicting age at menopause in white women. Fertil Steril. 2006;85(2):451-454.
7. Bastian LA, Smith CM, Nanda K. Is this woman perimenopausal? JAMA. 2003;289(7):895-902.
8. Murabito JM, Yang Q, Fox C, Wilson PW, Cupples LA. Herita- bility of age at natural menopause in the Framingham Heart Study. J Clin Endocrinol Metab. 2005; 90(6):3427-3430.
9. Randolph JF, Sowers M, Gold EB, et al. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. J Clin Endocrinol Metab. 2003;88(4): 1516-1522.
10. Gallicchio L, Visvanathan K, Miller SR, et al. Body mass, estrogen levels, and hot flashes in midlife women. Am J Obstet Gynecol. 2005;193(4):1353-1360.
11. Dennerstein L, Dudley E, Burger H. Are changes in sexual functioning during midlife due to aging or menopause? Fertil Steril. 2001;76(3):456-460.
12. Dennerstein L, Lehert P, Burger H. The relative effects of hormones and relationship factors on sexual function of women through the natural menopausal transition. Fertil Steril. 2005;84(1):174-180.

back to top