New scientific research on hormone replacement therapy beyond age 65

Information to help women make informed choices

Each year the American Board of Obstetrics and Gynecology selects research articles deemed important to patient care. 

This year an article by Baik and colleagues entitled:

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses expands our understanding of the benefits and risks of HRT over time.  

The study examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular(CV) diseases, and dementia. Outcomes of 11 million women (1.5 million hormone users, 9.5 million nonusers) followed over 13 years was presented. 

The five cancer outcomes included breast, lung, uterine, colorectal, and ovarian cancers. The six CV outcomes included ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, and acute myocardial infarction(heart attack).

For women taking HRT after age 65, the use of estrogen only therapy was associated with significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, congestive heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction and dementia.

For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer, but such risk can be mitigated using a low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer, ovarian cancer, ischemic heart disease, congestive heart failure, and venous thromboembolism, whereas E+ progesterone exhibited risk reduction only in congestive heart failure.

The authors concluded: Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with estradiol rather than conjugated estrogen(horse product).

This article adds to our growing understanding of the risks and benefits of HRT. 

Is estrogen good for the heart?

The answer appears to be yes. Estrogen only HRT showed improved outcomes for most of the cardiovascular problems analyzed in this study. Transdermal and vaginal estrogen showed better results than oral estrogen. When a Progestin or Progesterone is also taken the benefits are reduced.

Does estrogen cause cancer?

Estrogen does not appear to increase cancer risk. It appears to protect users from developing breast, lung and colorectal cancer. The findings confirm those of other studies that came to similar conclusions thus strengthening our knowledge of this benefit.

Does Progesterone increase the risk of breast cancer?

Yes, it appears so. For several years there has been a debate about Progestins(synthetic progesterone) and Progesterone(the natural molecule). Smaller studies concluded Progesterone does not increase breast cancer risk. This very large study suggests it does increase risk. Progestin also increased breast cancer risk except for those women using a low dose of transdermal estradiol or vaginal estrogen.

What is the best way to prescribe estrogen?

Transdermal estrogen appears to be a safer way to prescribe. Lower dose estrogen fared better than higher doses. Not all women tolerate low dose estrogen. Individuality in prescribing is important. Younger women just entering menopause may need higher doses to start with. A strategy of lowering the dose gradually after 60 makes sense.

Does vaginal estrogen work as well as a patch?

No. Vaginal estrogen is a low dose cream women use for dryness causing painful intercourse. The low dose does not treat hot flashes like a patch would. Even at this low dose estrogen had benefits.

This study creates a lot of questions.

If there was a transdermal Progesterone or Progestin how would that impact risk?

The only way to get transdermal Progesterone is to purchase a product developed for fertility(get the insurance company to pay for that when you’re 55) or have a compounded Progesterone cream made. Hopefully someone will bring a transdermal Progesterone cream or patch to market.

There is a commercially available estradiol/levonorgestrel(Progestin) patch. Also there is data on using the levonorgestrel IUD for HRT with estradiol. Because these have not been in use long, time is needed before we may get answers to the questions on cancer and cardiovascular impact.

How does this study help women decide if HRT is right for them?

The data suggests estrogen only HRT has significant benefits. For women who have had a hysterectomy estrogen appears to have a great upside and not a lot of downside. That does not mean you should have a hysterectomy.

I would encourage those women to consider a low dose patch after 50. Not only for the beneficial outcome shown in this study, but also for prevention of bone loss, vaginal dryness and loss of libido. Vaginal estrogen has benefits and helps vaginal dryness but not bone loss.

Women on E+P HRT had benefits, just not quite like women on estrogen only. Because women are living longer and HRT prevents bone loss, they should give it consideration. My patients have told me libido improves when they start HRT. Vaginal estrogen does not require Progesterone and prevents vaginal dryness and pain with intercourse. I would recommend vaginal estrogen at a minimum for the benefits demonstrated in this study

This information could help younger women when deciding between a hysterectomy or a non-hysterectomy procedure for fibroids, ovarian cysts or prolapse. A woman should not have a hysterectomy unless she has had a thorough discussion of the risk and benefits.