Menopause: The Transition

Menopause is an obvious marker of ovarian aging. Chronological age is a poor predictor of when menopause occurs, and women vary widely in their menopausal transition. Last month I mentioned that the North American Menopause Society (NAMS) defines menopause as 12 months after the final menstrual period (FNP). In 2011 a multidisciplinary, multinational consensus workshop, The Stages of Reproductive Aging Workshop (STRAW), divided the menopausal transition into two premenopausal and two post- menopausal time frames. The importance is how these time frames relate to the symptoms patient’s experience and how those symptoms might be managed medically. The EARLY PRE-MENOPAUSE transition’s time frame is variable and defined by the persistent difference of 7 days or more in cycle length on consecutive cycles. The LATE PRE-MENOPAUSE transition typically lasts 1-3 years and is characterized by cycles interspersed by 60 consecutive days (or longer) of not bleeding. In the early pre-menopause transition extra eggs can be recruited mid cycle which can lead to an overproduction of estrogen which may result in breast pain, migraine, and heavy bleeding. These wide fluctuations in hormone levels may also be one of the triggers that lead to hot flashes and night sweats (which can occur during the day).

The final menstrual period is always determined by looking backwards 12 months. This is the beginning of an EARLY POST-MENOPAUSE that typically lasts for 2-3 years. Vasomotor symptoms are most likely occurring by this time if not already starting in late pre-menopause. The end of the EARLY POST-MENOPAUSE is about 3-6 years after the FNP and is typically when estradiol levels are low and stabilize. The LATE POST-MENOPAUSE begins 5-6 years after the FMP and continues for your remaining life span. Further changes in reproductive endocrine function are limited, and somatic aging predominates. This phase can be marked by increasing genitourinary symptoms (burning, dryness, painful intimacy, and bladder infection like symptoms), which may not end, unlike hot flashes, which for most women may only last 6-7 years.

The Women’s Health Initiative (WHI) was one of the largest U.S. prevention studies including ~161K menopausal women. It was the first (and probably last) randomized controlled study intended to look and the benefits (reduction in hot flashes and genitourinary symptoms) and risk (breast cancer and stroke) of hormone replacement therapy compared to placebo. Launched in 1991 with the first results released in 2002, the WHI ( focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. Since the trial ended in 2005, more than 115K WHI participants have continued providing health information that is being used to investigate a variety of key women’s health questions. More then 90K of these women are still alive and in active follow-up across all 50 states.

In July 2002, one component of the WHI, which studied the use of estrogen (E) + progesterone (P) in a woman who had a uterus, was stopped early because the health risks exceeded the health benefits. The main reason for stopping the E+P study was because of a 26% increase in the risk for breast cancer.  In March 2004, a second component of the WHI, which studied estrogen-only therapy in women who no longer had a uterus (prior hysterectomy), was stopped early. This was primarily because of an increase risk for strokes. What women heard around the world for the first time was that this elixir called hormone replacement therapy (HRT) obtained from the fountain of youth was potentially harmful. Overnight the majority of postmenopausal women stopped their HRT cold turkey out fear that it was harmful. This memory still rings loud and clear when I ask women about their first impression when I say the words hormone replacement therapy.

Yes it was true; this was the first time since HRT had been promulgated in Robert A. Wilson MD’s 1968 book Feminine Forever (supported by Wyeth, a drug company making Premarin/Provera that was sold to Pfizer pharmaceuticals in 2009), post-menopausal hormones may be hazardous to your health. Ten years has elapsed since the WHI trial was closed allowing more nuanced conclusions. The current NAMS consensus on HRT use is based on the age of the patient and when in her menopausal transition she started HRT. I won’t give away the ending of the story if I say that HRT should be offered only to those women who are having symptomatic hot flashes or genitourinary changes.  NAMS is dedicated to helping clinicians and menopausal patients understand the significant benefits and small but reasonable risks in the women who choose to take HRT. I will delve into these nuances next month so stay tuned.

Dr. Timothy Leach

You Might Also Enjoy...