Oral contraceptives as replacement HT
Dr. Faubion: Would you comment on use of a birth control pill in this circumstance? Would it be optimal to use a postmenopausal HT regimen as opposed to a birth control pill or combined hormonal contraception?
Dr. Kapoor: In this younger population, sometimes it seems like a more socially acceptable decision to be on a birth control option than on menopausal HT. But there are some issues with being on a contraceptive regimen. One is that we end up using estrogen doses much higher than what is really needed for replacement purposes. It is also a nonphysiologic way of replacement in another sense—as opposed to estradiol, which is the main hormone made by the ovaries, the hormonal contraceptive regimens contain the synthetic estrogen ethinyl estradiol for the most part.
The other issue that is based on some weak evidence is that it appears that the bone health outcomes are probably inferior with combined hormonal contraception. For these reasons, regimens that are based on replacement doses of estradiol are preferred.
Dr. Faubion: Right, although the data are somewhat weak, I agree that thus far it seems optimal to utilize a postmenopausal regimen for various reasons. Dr. Kaunitz, anything to add?
Dr. Kaunitz: Yes, to underscore Dr. Kapoor’s point, a common oral contraceptive that contains 20 µg of ethinyl estradiol is substantially more estrogenic than 1.0 or 2.0 mg of micronized oral estradiol.
Also consider that a 20-µg ethinyl estradiol oral contraceptive may increase the risk of venous thromboembolism more than menopausal doses of oral estradiol, whether it be a micronized estradiol or conjugated equine estrogen.
Dr. Faubion: So the risk may be greater with oral combined hormonal contraception as well?
Dr. Kaunitz: One thing we can do is explain to our patients that their ovaries, prior to surgery or prior to induced menopause, were making substantial quantities of estradiol. Whether we prescribe a patch or oral micronized estradiol, this estrogen is identical to the hormone that their ovaries were making prior to surgery or induced menopause.
Breast cancer concerns
Dr. Faubion: Let’s consider a more complicated case. A 35-year-old woman has an identified BRCA1 mutation; she has not had any cancers but has undergone risk-reducing BSO and her uterus remains. Is this woman a candidate for HT? At what dose, and for how long? Dr. Kaunitz, why don’t you start.
Dr. Kaunitz: That is a challenging case but one that I think our readers will find interesting and maybe even provocative.
We know that women with BRCA1 mutations, the more common of the 2 BRCA mutations, have a very high risk of developing epithelial ovarian cancer at a young age. For this reason, our colleagues in medical oncology who specialize in hereditary ovarian/breast cancer syndromes recommend prophylactic risk-reducing—and I would also say lifesaving—BSO with or without hysterectomy for women with BRCA1 mutations.
However, over the years there has been tremendous reluctance among physicians caring for BRCA patients and the women themselves—I use the term “previvors” to describe BRCA carriers who have not been diagnosed with breast or ovarian cancer—to use HT after BSO because of concerns that HT might increase breast cancer risk in women who are already at high risk for breast cancer.
I assume, Dr. Faubion, that in this case the woman had gynecologic surgery but continues to have intact breasts. Is that correct?
Dr. Faubion: That is correct.
Dr. Kaunitz: Although the assumption has been that it is not safe to prescribe HT in this setting, in fact, the reported cohort studies that have looked at this issue have not found an elevated risk of breast cancer when replacement estrogen, with or without progestin, is prescribed to BRCA1 previvors with intact breasts.
Given what Dr. Kapoor said regarding the morbidity that is associated with BSO without replacement of physiologic estrogen, and also given the severe symptoms that so many of these young menopausal women experience, in my practice I do prescribe estrogen or estrogen-progestin therapy and focus on the higher target doses that we discussed for the earlier case patient who had a hysterectomy for abnormal uterine bleeding with adenomyosis.
Dr. Faubion: Dr. Kapoor, do you agree with this approach? How long would you continue therapy?
Dr. Kapoor: First, in this BRCA1 case we need to appreciate that the indication for the BSO is a legitimate one, in contrast to the first case in which the ovaries were removed in a patient whose average risk of ovarian cancer was low. It is important to recognize that surgery performed in this context is the right thing to do because it does significantly reduce the risk of ovarian cancer.
The second thing to appreciate is that while we reduce the risk of ovarian cancer significantly and make sure that these patients survive longer, it’s striking a fine balance in that you want to make sure that their morbidity is not increased as a result of premature estrogen deprivation.
As Dr. Kaunitz told us, the evidence that we have so far, which granted is not very robust but is fairly strong observational evidence, suggests that the risk of breast cancer is not elevated when these patients are treated with replacement doses of HT.
Having said that, I do have very strong discussions with my patients in this category about having the risk-reducing bilateral mastectomy also, because if they were to get breast cancer because of their increased genetic predisposition, the cancer is likely to grow faster if the patient is on HT. So one of my counseling points to patients is that they strongly consider bilateral mastectomy, which reduces their breast cancer risk by more than 90%. At the same time, I also strongly endorse using HT in replacement doses for the reasons that we have already stated.
Dr. Faubion: Continue HT until age 50 or 52?
Dr. Kapoor: Definitely until that age, and possibly longer, depending on their symptoms. The indications for treating beyond the age of natural menopause are much the same as for women who experience natural menopause.
Dr. Faubion: That is assuming they had a bilateral mastectomy?
Dr. Kapoor: Yes.
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