Last month’s column ended with a reference to 2012 Hormone Therapy Position Statement of The North American Menopause Society (NAMS). The intent of that statement was to clarify the benefit-risk ratio of estrogen therapy (ET) vs. estrogen-progestogen therapy (EPT) of menopause-related symptoms and disease prevention. NAMS acknowledged that no single trial data could be extrapolated to all women. However, because the Women’s Health Initiative (WHI) was the first randomized controlled trial (RCT) of post-menopausal women using hormone therapy (HT), these findings were given prominent consideration. A randomized controlled trial (RCT) is considered the gold standard for scientific studies because subjects are randomly assigned to either a treatment group or a placebo group. The two groups respective outcomes are then compared for a specific question (i.e. breast cancer risk in HT users vs. HT non users). Prior to the WHI, most studies looking at the benefit-risk of HT were largely observational studies. This means that a group of women using HT were “observed” over time and outcomes were evaluated. Observational studies have limitations and conclusions not infrequently disputed when a RCT asks the same question.
NAMS pointed out that the WHI RCT had several characteristics that limit generalizing the findings to all post-menopausal women. These include the use of only one route of administration (oral), only one formulation of estrogen (conjugated equine estrogen “premarin”), and only one progestogen (medroxyprogesterone acetate “Provera”). Current HRT preparations use different estrogens and come in transdermal, transvaginal products at many different dosages. Observational studies of HT often focused on symptomatic, recently postmenopausal women, whereas the WHI enrolled healthy postmenopausal women aged 50 to 79 years in a prevention trial. While different studies have the strengths and weaknesses, RCT’s are generally given more weight as to the strength of their conclusions.
SWAN (Study of Women’s Health Across the Nation swanstudy.org) started in 1994 with the intention of being a multi-site, observational, longitudinal epidemiologic study designed to examine the health of women during their middle years.
The goal of SWAN's research is to help scientists; health care providers and women learn how mid-life experiences affect health and quality of life during aging.
Most women equate the duration of their menopause to the time period they are having hot flashes. The SWAN study helped clinicians understand what many patients already knew, and that is hot flashes can last on average up to 7.5 years, of which many of those years occur before their final menstrual period. Interestingly, SWAN also found that race or ethnic background does make a difference. Women of African American descent on average could expect up to 10 years of hot flashes compared to Hispanic women who had more then Caucasian women.
The NAMS 2012 position statement said that estrogen therapy (ET) with or without a progestogen is the most effective treatment of menopause-related hot flashes and their potential consequences, such as diminished sleep quality, irritability, difficulty concentrating, and subsequently reduced quality of life (QOL). Treatment of moderate to severe vasomotor symptoms remains the primary indication for initiating HT. Progestogen alone also reduces hot flashes but not as effectively as estrogen does.
Since the WHI trial, newer transdermal formulations and lower dose options have become available. Most clinicians are comfortable using transdermal estrogen (available in patch, gel, cream, mist) as they are felt to have greater efficacy with less cardiovascular risk. I tell patients that estrogen has the potential to reduce hot flashes by ~80% within 4-6 weeks. Relizen is a botanical product used extensively in Europe for the treatment of hot flashes. European and North American studies on Relizen, demonstrate a 60% reduction in hot flashes after 3 months and most importantly, no reduction in the efficacy of tamoxifen in breast cancer patients. In Europe this product requires a doctors prescription but in the USA, it is considered a botanical and thus able to be purchased over the Internet. Relizen is different compared to other OTC products, in that individual pills come with lot numbers and expiration dates to guarantee purity and safety. I am not endorsing this product and only pass along information published in peer-reviewed journals. In future columns I will share other benefit-risk ratio of ET & EPT (genitourinary symptoms, sexual function, osteoporosis, QOL, etc.) and the significance of when a woman starts taking hormones: the timing hypothesis.