Women around the world are united by menopausal upheaval. It’s that phase in every woman’s life when her menstrual cycle comes to an end, her ovaries stop producing estrogen and progesterone, and she subsequently starts experiencing disconcerting physical and emotional changes. With this hormonal diminution, menopausal changes start to surface, and they fall into two categories: short-term changes like hot flashes, vaginal dryness, difficulty to fall asleep and mood swings, and long-term changes such as bone loss and coronary heart disease. The most common menopausal symptoms are vasomotor symptoms (hot flashes and night sweats) and vaginal dryness.
The average age of menopause in the United States is 51, but that varies from one woman to another. There are specific factors that influence the natural age of menopause, such as smoking, chemotherapy, ovarian surgery and ethnicity. For example, women undergoing chemotherapy or ovarian surgery, those of Hispanic and African-American descent, and women who smoke have an earlier onset of menopause.
For decades, healthy postmenopausal women have been using menopausal hormone therapy, or MHT, to ease the symptoms following menopause. In her well-researched book, “The Estrogen Elixir,” Elizabeth Siegel Watkins narrates the interplay between society and science in determining women’s perspective towards MHT, and in turn their use of MHT in the enduring pursuit to fight aging using the “wonder hormone,” estrogen. There are two forms of MHT: estrogen plus progestogen therapy in women with an intact uterus, and estrogen-only therapy, or ET, in hysterectomised women. Estrogen alone stimulates the uterine lining (the endometrium) to proliferate, whereas progesterone opposes the estrogenic stimulatory action and acts as a checkpoint to prevent excessive proliferation (endometrial hyperplasia) and the subsequent risk of developing uterine cancers (endometrial cancers). That’s why a progestogen (either as an isomer of progesterone or a synthetic progestin) is usually given to women with an intact uterus.
[See: 11 Changes Women Go Through in Menopause.]
Despite the accumulative literature, controversy spans MHT, and women are left conflicted. It’s imperative to recognize that controversies are foreseen in light of several major studies that have different populations and different combinations of MHT, and each draws conclusions based on that with regards to risks and benefits of MHT. Such controversies are opportunities in disguise, but only if we connect the dots and successfully define and seize the window of opportunity” in MHT. That’s the period in every postmenopausal woman’s life where she can harness the most favorable benefit-risk ratio of MHT against major diseases.
Defining and Seizing the “Window of Opportunity”
The North American Menopause Society, the National Institute for Health and Care Excellence, the Endocrine Society and the International Menopause Society all released consensus and position statements to better guide women on MHT. In general, all seem to agree that women within the first 10 years after menopause (younger than 60 years), with no contradictions to MHT use, derive benefits from ET of MHT in regards to reductions in cardiovascular disease, osteoporotic fractures, colorectal cancer, Type 2 diabetes and overall mortality. Women older than 60 have a less favorable benefit-risk ratio. Benefit-risk perspective toward EPT is debatable, probably because of the type of progestogen used.
The story unfolds differently for MHT and breast cancer. Numerous studies, including the famous Women’s Health Initiative clinical trials, have shown that women at five years or more after menopause derive benefit from estrogen with dramatic decreases in breast cancer incidence and breast cancer-related mortality BCM. For the EPT regimen and its association with breast cancer risk, the progestogen used seems to be one of the major players in determining benefits or risks. Leading by example, the WHI trial and their follow-up showed that postmenopausal women with a uterus on EPT have an increased breast cancer incidence and BCM. The progestin used in the WHI trial was medroxyprogesterone acetate, which increases the risk of breast cancer, whereas a recent Finnish study published in Menopause showed that women on EPT had a decrease in BCM. Two out of the three progestins studied in the Finnish study are: norethisterone acetate and dydrogesterone, both of which were shown to decrease the risk of breast cancer compared to MPA.
The window of opportunity for unified osteoporosis and cardiovascular benefits, which goes hand-in-hand with protection against breast cancer, lies around 55 to 60 (five years after menopause and under 60 years).
[See: What to Eat and Drink During Menopause.]
The “Timing Effect” and Breast Cancer
The “timing effect” between menopause and the initiation of MHT remains crucial to harness benefits over risks. Women given ET in five years or less after menopause have a greater risk of breast cancer, whereas women given MHT at 10 years or more after menopause have a greater risk-benefit ratio in regards to other diseases (i.e. cardiovascular diseases).
In general, the duration of MHT is not specified, but it’s advised not to be long term. According to the Food and Drug Administration and the North American Menopause Society, MHT is given in the form of the lowest doses and at the shortest intervals aimed at moderate to severe menopause-symptom relief. The Endocrine Society and NAMS algorithm even suggested screening women for the risk of cardiovascular disease and breast cancer before the onset of menopause, when considering MHT for the treatment of moderate to severe hot flashes. Women on MHT are advised to have regular visits to see the doctor and decide whether they still need MHT or not. For breast cancer risk and the duration of MHT, the WHI trials had an average of six years for the ET regimen and five years for the EPT regimen, whereas the Finnish study showed that BCM was reduced in all MHT users with exposure for, at most, five years.
Every Woman Has a Choice
In the late 1960s, the use of estrogen became very popular with the erroneous concept that it would make women “young forever.” After 1988, its use was further increased when it was approved by the FDA for the prevention of osteoporosis. By the 1990s, its use peaked even more as observational studies showed that MHT reduces coronary heart disease and the risk of Alzheimer’s disease. However, estrogen consumption declined after the WHI trial released their conclusions that a MHT of ET and MPA (as EPT) increased the risk of coronary heart disease and breast cancer. This shows the “domino effect” of data and awareness.
The wise thing to do is not to completely disregard MHT as a whole, but rather explore the reason behind the evident harm and provide “safer EPT” regimens or safer MHT approaches, which in turn optimizes MHT and still benefits women. Every woman has a choice to make with her physician on the timing to start MHT, the duration of use and the combinations of MHT. It’s important to make smart choices based on the latest guidelines and what has proven to be safe. For example, women should use low-dose transdermal estrogen instead of oral administration, which has a lower risk of venous thrombosis and strokes. Women have a choice in the fine yet crucial details; knowledge equals safer choices.
Estrogen: a Phoenix From the Ashes
Estrogen has become like a “Phoenix from the Ashes.” It was once feared and abandoned after the WHI trials, and now it has been proven to be very favorable and beneficial as a component of MHT. Studies from Denmark, Finland and the United States all confirm that ET is definitely favorable in MHT. A 20 to 40 perent reduction in all-cause mortality in women using ET was noted in several observational studies. Also, a Bayesian meta-analysis based on several observational and randomized clinical trials showed a 28 percent mortality reduction. This is only noted within the first 10 years after menopause. Nonetheless, women should take a progestogen while taking estrogen to prevent the development of endometrial cancers. Therefore, it’s safer to choose a progestogen hand in hand with the estrogen, but what’s really paramount is the choice of a safe progestogen.
[See: What Not to Say to a Breast Cancer Patient.]
ET and EPT: It Takes Two Flints to Make a Fire
Women can be given ET and a “safe EPT.” This is advised with the lowest effective doses, for the least time (In the case of breast cancer risk, MHT duration has not exceeded five years for EPT and six years for ET), and at the appropriate age after menopause within the “window of opportunity,” if women wish to harness the highest benefit-risk ratio during their biological lives. Indeed, ET and EPT are the two flints to improve women’s health in preventing osteoporosis and cardiovascular diseases while protecting against breast and endometrial cancers.
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Menopausal Hormone Therapy: Controversy or Opportunity? originally appeared on usnews.com
