Usefulness of monitoring estradiol levels for dosage adjustment
Dr. Faubion: That’s a great point, and again it is important to emphasize that we are aiming to recreate the premenopausal hormonal milieu. If you were to check estradiol levels, that would be aiming for a premenopausal range of approximately 80 to 120 pg per mL. Dr. Kapoor, is there utility in monitoring estrogen levels?
Dr. Kapoor: Great question, Dr. Faubion, and as you know it’s a loaded one. We base this on empiric evidence. We know that if the hormonal milieu in a young patient is changed to a postmenopausal one, her risk for many chronic conditions is increased. So if we were to reinstate a premenopausal hormonal milieu, that risk would probably be reduced. It makes good sense to target an empiric goal of 80 to 120 pg per mL of estradiol, which is the average estradiol level in a premenopausal woman. If you were to ask me, however, are there randomized, controlled trial data to support this practice—that is, if you target that level, can you make sure that the risk of diabetes is lower or that the risk of heart disease is lower—that study has yet to be done, and it may not ever be done on a large scale. However, it intuitively makes good sense to target premenopausal estradiol levels.
Dr. Faubion: When might you check an estradiol level in this population? For example, if you are treating a patient with a 0.1-mg estradiol patch and she still has significant hot flashes, would it be useful to check the level?
Dr. Kapoor: It would. In my practice, I check estradiol levels on these patients on an annual basis, regardless of symptoms, but definitely in the patient who has symptoms. It makes good sense, because sometimes these patients don’t absorb the estrogen well, particularly if administered by the transdermal route.
A general rule of thumb is that in the average population, if a patient is on the 0.1-mg patch, for example, you would expect her level to be around 100. If it is much lower than that, which sometimes happens, that speaks for poor absorption. Options at that point would be to treat her with a higher dose patch, depending on what the level is, or switch to a different formulation, such as oral.
In instances in which I have treated patients with a 0.1-mg patch for example, and their estradiol levels are undetectable, that speaks for very poor absorption. For such patients I make a case for switching them to oral therapy. Most definitely that makes sense in a patient who is symptomatic despite treatment. But even for patients who don’t have symptoms, I like to target that level, acknowledging that there is no evidence as such to support this practice.
Dr. Faubion: Dr. Kaunitz, do you want to add anything?
Dr. Kaunitz: Yes, a few practical points. Although patches are available in a wider array of doses than oral estrogen formulations, the highest dose available is 0.1 mg. It’s important for clinicians to recognize that while checking serum levels when indicated can be performed in women using transdermal estradiol or patches, in women who are using oral estrogen, checking blood levels is not going to work well because serum estrogen levels have a daily peak and valley in women who use oral versus transdermal estradiol.
I also wanted to talk about progestins. Although many patients who have had a BSO prior to spontaneous menopause also have had a hysterectomy, others have an intact uterus associated with their BSO, so progestins must be used along with estrogen. And if we are using higher-than-standard doses of estrogen, we also need to use higher-than-standard doses of progestin.
In that classic 53-year-old woman I referred to who had spontaneous normal menopause, if she is taking 1 mg of estradiol daily, or a 0.05-mg patch, or 0.625 mg of conjugated equine estrogen, 2.5 mg of medroxyprogesterone is fine. In fact, that showed excellent progestational protection of the endometrium in the Women’s Health Initiative and in other studies.
However, if we are going to use double the estrogen dose, we should increase the progestin dose too. In some of my patients on higher estrogen doses who have an intact uterus, I’ll use 5 or even 10 mg of daily medroxyprogesterone acetate to ensure adequate progestational suppression.
Dr. Faubion: Another practical tip is that if one is using conjugated equine estrogens, measuring the serum estradiol levels is not useful either.
Dr. Kaunitz: I agree.
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