Menopause Hormone Therapy Still Divides Physicians

 Rachel Weinerman, MD, a reproductive endocrinologist at Case Western Reserve University and University Hospitals in Cleveland, explains why menopause hormone therapy remains controversial more than 20 years after the landmark Women's Health Initiative (WHI) trial.

She discusses what clinicians have learned about hormone replacement therapy since then, which patients may benefit the most, and how different formulations may alter the risk-benefit balance.

Menopause hormone therapy, or hormone replacement therapy, is essentially a way to give women a combination of either estrogen and progestin or some sort of progestin activity, it's called progesterone, or estrogen alone, depending on whether or not she has a uterus. And the goal is to alleviate the symptoms that occur during menopause when a woman's ovaries stop producing the hormones estrogen and progesterone.

That time period actually could be a while. It could be 5 to 10 years. The hormones are fluctuating as the ovaries stop producing those hormones, and that can cause very bothersome symptoms. So giving back the hormones that the ovary naturally produces -- specifically estrogen and progesterone -- can alleviate those symptoms. And that really was a prevailing view for many, many years in the healthcare community, that we should be giving women hormone replacement therapy. It helps them feel better, and it probably would help them long-term, and that's what smaller studies showed.

However, the Women's Health Initiative study was a large randomized controlled trial, and that demonstrated that giving women hormonal replacement therapy did not help prevent some of the long-term outcomes like cardiovascular disease problems, but it did increase the risk of breast cancer. So for that reason, the trial actually was stopped earlier than planned. And once that was published, many physicians and patients totally turned around and said, "Wait a second, we shouldn't be giving this hormone therapy to women because it's dangerous."

In the 20 years since that study has come out, we have learned a lot. Age matters and indication matters. So in that study, women were started on hormone replacement therapy at all ages, and what we've since learned is that women who start hormone replacement therapy under the age of 60 or within 10 years from the onset of menopause, have a much more favorable risk-to-benefit profile.

The other thing that we learned is that the reason for starting hormone replacement therapy, or the indication, matters. So for women who start hormone replacement therapy because they have significant symptoms like hot flashes or vaginal dryness, that actually is more beneficial than women who are starting it in an attempt to prevent the long-term complications of having low estrogen.

The formulations that we used have also changed. In that study, the estrogen that was used is actually something called Premarin [conjugated estrogens]. It was an estrogen that we had at the time, and we still have, but it's not a hormone that is naturally produced by women. It was actually a combination of horse estrogens. And the progestin that we used in that study was a synthetic progesterone that we call a progestin. And there were some health risks that were found with that combination.

Now we use what's called bioidentical hormone, so we use a combination of estradiol -- it's the same hormone that's naturally produced by women's ovaries -- and natural progesterone. Those hormone combinations may be more similar to what's actually produced by women's ovaries and may give different health risks. And that combination has not been studied as significantly as the WHI.

So the WHI is still a very important study that should guide treatment going forward. One of the most important things that we learned from the WHI study is that it's not so clear-cut that giving estrogen therapy or a combination of estrogen and a progestin therapy to women is always going to be beneficial. There are definite risks that come from giving hormone replacement therapy, specifically for women who have a high risk of breast cancer. We see that in that study, a combination of estrogen and progestin increased the risk of breast cancer. So for women who have risks, it may not be the best therapy for them.

Additionally, it didn't improve cardiovascular health in the way that we expected. So what we have learned from that study is that we should be careful about who we give hormone replacement therapy to. It is indicated for many women, but not all. And I think the enduring lesson of the WHI study is that menopause hormone therapy can be a very effective and important treatment for women, but it has to be an individualized decision between a woman and her physician based on her own specific needs and risk factors.

There's a difference in safety between what we call systemic hormone therapy and vaginal or local hormone therapy. So we can give very low-dose estrogen therapy to women vaginally, and that can help relieve many of the symptoms that come from low estrogen, specifically sexual dysfunction and vaginal atrophy that can lead to painful urination and painful intercourse. And we can give that therapy very safely, even to women who don't want to take on the risks of having what we call systemic hormone therapy, which is higher-dose hormone therapy that they would take either by mouth or by a skin patch.

It is a very important topic. All women are going to experience menopause at some point in their lives, and it's a problem that I'm happy is coming to the forefront of our conversation, and I really hope that we can improve the lives and health of women going forward.

https://www.medpagetoday.com/obgyn/hrt/116842