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Menopause Medley - Your Questions Answered

I received quite a few questions over the holidays so I thought I'd address a few of them in this post.


1."My doctor told me that hormone therapy causes breast cancer and blood clots. Why would anyone take it?"


Good question. It's likely that the doctor in question is referring to findings from the Women's Health Initiative (WHI) study and is relying on outdated talking points. The bottom line is that the information provided by the doctor is incorrect. Let's delve into what the doctor should have told you.


The WHI, among the largest women's health studies ever conducted, offered valuable insights. However, widespread media coverage of select data points without adequate context led to a rapid decline in the use of Menopausal Hormone Therapy (MHT). Despite good intentions, the study's design and findings have faced criticisms over the years:


As a reminder, MHT includes estrogen alone (ET) or estrogen with a progestogen (EPT). The women in the WHI study were given oral conjugated estrogens and methoxprogesterone acetate.. Current prescriptions for MHT more often include 17-beta-estradiol which is identical to the structure of estradiol produced by the ovaries, and micronized progesterone, which is structurally identical to the progesterone produced by the ovaries. Additionally, studies have concluded that any increased blood clot risk can be ameliorated by delivery of estrogen transdermally instead of orally.


The WHI predominantly focused on women starting MHT after age 60 or 10-20 years post-menopause. Only 30% of participants were less than 60, but results were generalized to all ages. When data from women aged 50-59 was analyzed separately, it was clear that the risks of using MHT in that population were not as significant. Current guidelines recommend initiating MHT under age 60 and/or within 10 years of menopause.


The study presented relative risks instead of absolute risks. Stick with me because this is important. If there's a 0.37% incidence of cardiovascular disease in 10,000 women taking MHT, it means 37 women have cardiovascular disease. Comparatively, if the non-MHT group has an incidence of 0.30%, the total women with cardiovascular disease is 30. Therefore, the actual increase in cardiovascular disease among MHT users is an extra 7 in 10,000 women or a 0.07% increase in absolute risk. Unfortunately, the WHI study authors reported that there was a 29% increase in relative risk, which seems high, instead of reporting the equally accurate 0.07% increase in absolute risk, which is incredibly low.

Media hype often centered on data that was not statistically significantly different between MHT and non-MHT users. For instance, a 26% increase in relative risk of invasive breast cancer in the MHT group was cited repeatedly, even though it did not represent a statistically different risk than non-MHT users.


Subsequent research and re-evaluation in studies with women under 60 have led to different conclusions about the WHI data and new MHT recommendations from major women's health medical societies.


MHT is associated with an increased absolute risk of less than 10/10,000/yr (rare) for blood clots (if estrogen is given orally) and gallbladder disease. EPT also confers a rare risk of stroke and breast cancer. Note, however, that the absolute risks of all-cause mortality, fracture, and diabetes (and breast cancer for women who take ET) are reduced in women younger than 60 who take MHT.


MHT is FDA-approved to treat hot flashes, prevent osteoporosis in menopausal women, and to treat genitourinary symptoms (GSM). Off-label uses of MHT include addressing sleep disturbance and sexual dysfunction. Estradiol also can have positive effects on skin moisture and thickness and reduce wrinkles. Data exists that it can alleviate joint pain and stiffness.


In summary, the risks of MHT in women less than 60 have been overstated, causing many women to endure unnecessary suffering from menopause symptoms. Women age 50-59 experiencing menopause symptoms are generally suitable candidates for MHT. For those who cannot or prefer not to take MHT, non-hormonal options are increasingly available. Women should consult a menopause specialist for personalized advice and make informed decisions about their treatment. The directory of The Menopause Society is a valuable resource for finding a specialist in your area.


2. "I read that estrogen with progesterone has a higher risk that estrogen alone. And I understand that most bothersome symptoms are the result of low estrogen. Why, then, should I use progesterone?"


It's likely that you've come across information about the WHI study, which indicated that women using Menopausal Hormone Therapy (MHT) containing both estrogen and progestogen (EPT) faced a slightly increased risk of breast cancer compared to those using MHT with only estrogen (ET). To put this increased risk into perspective, the likelihood of developing breast cancer caused by use of EPT is only marginally higher than the risk associated with drinking one glass of wine per day. It's less risky than consuming two glasses of wine daily and roughly equivalent to the risk associated with being obese.


Importantly, women with a uterus are advised to take a progestogen along with estrogen to prevent uterine hyperplasia. This precaution is essential because, in the absence of progestogen, continuous estrogen use can lead to a buildup of uterine tissue, potentially resulting in cancer. Although some doctors recommend daily progestogen alongside estrogen, it is equally effective to take it only for two weeks each month. However, due to the challenge of remembering specific weeks, many women opt for daily intake. It's important to note that women without a uterus can safely take estrogen without progestogen.


Beyond preventing uterine hyperplasia, progestogens offer various benefits. Menopausal women experience a significant decrease in their progesterone level, which is important since natural progesterone improves pain tolerance, alleviates joint pain, and provides relief from anxiety. Progesterone also plays a crucial role in bone health by reducing the rate of bone absorption and minimizing calcium loss in urine. Additionally, it has a calming effect on the brain, promoting anti-anxiety responses. Micronized progesterone is often prescribed to menopausal women to help with joint pain, brain fog, anxiety, and disrupted sleep. There also is evidence that progesterone alone, without estrogen, can improve symptoms like hot flashes and night sweats and reduce irregular bleeding in peri-menopausal women. You can read more about progesterone here.


It's worth mentioning an exception to the general rule about the need for progestogen use in women with a uterus who are taking estrogen. The new drug Duavee is composed of conjugated estrogen and bazedoxifene (a selective estrogen receptor modulator or SERM). Bazedoxifene acts as an estrogen antagonist in the uterus, eliminating the need for additional progestogen to protect the uterus during its use.


As is always my recommendation, women should talk with their doctors to determine the right treatment for their specific situation.



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