The ovaries produce three types of estrogen: 17 beta-estradiol, estrone, and estriol. Premenopausally, the predominant estrogen produced by the ovary is 17-beta estradiol, or E2. It is converted back and forth to estrone, E1, which is made in the fat and is the predominant estrogen postmenopausally. All of the patches, and several oral formulations such as Estrace, are E2. When E2 is taken orally, much of it is converted to E1 in the gut. E1 and E2 essentially are equivalent in their level of estrogenic activity. Estriol, E3, is the weakest of the three estrogens and is predominantly made in the placenta during pregnancy. It is not conventionally prescribed and is available only through compounding pharmacies. Estriol is the predominant form of estrogen in Tri-Est and Bi-Est. Estriol, Tri-est, and Bi-est are frequently used and recommended by the alternative medicine community.
Conjugated equine estrogens are composed of more than 10 different molecules extracted from the urine of pregnant mares. This is a natural product but is not bioidentical or native. In addition to animal conjugated equine estrogen, a synthetic version, such as Cenestin, is available.
It is difficult to draw conclusions regarding options for the use of these hormones. The reasons for this are listed in Table 13.10.
Table 13.10 Reasons for Difficulty in Drawing Conclusions Regarding Use of Hormones
Drawing conclusions regarding options for the use of these hormones is challenging for a variety of reasons: 1.
It is essential to reinforce to patients that all hormones are not created equal. Different hormones have different effects. For example, estriol is often promoted as a hormone that does everything that conjugated equine estrogen does but with none of the risks. Given that it is a significantly weaker estrogen than conjugated equine estrogen, this is dubious and is not based in scientific evidence.
2.
Native or bioidentical hormones are rarely included in research protocols. The Women’s Health Initiative studied only conjugated equine estrogen (Premarin) and MPA (Provera). The Postmenopausal Estrogen-Progestin Intervention (PEPI) used only conjugated equine estrogen, but did compare it with micronized progesterone (and showed micronized progesterone to be as effective as medroxyprogesterone acetate at protecting the endometrium and better than medroxyprogesterone acetate at protecting the lipid benefits of estrogen).
3.
All forms of hormone therapy frequently are clumped together as one entity. The distinctions between the types of hormones studied are rarely made in the media and often not clear even in the medical literature. The coverage of the Women’s Health Initiative is a perfect example, as the media generalized its findings to hormone therapy, and even most information released by and for doctors did not clarify that the findings were regarding one specific form of estrogen combined with one specific form of progestin.
Progestins Bioidentical progesterone is available either through compounding pharmacies or through retail pharmacies as micronized progesterone, natural progesterone, or progesterone USP (brand name Prometrium). Medroxyprogesterone acetate (MPA) is a nonbioidentical progestin (i.e., its molecular structure is foreign to the body).
Bioidentical Estrogens E2, or 17 beta-estradiol, often is used interchangeably with conjugated equine estrogen. It is effective in relieving vasomotor symptoms, helps maintain bone, and improves the lipid profile. It is most bioidentical when delivered in the form of the patch because its oral form is converted to estrone in the gut. (The patch bypasses the liver and is not as beneficial in its effects on high-density lipoprotein and low-density lipoprotein, but it increases triglycerides to a lesser extent.) No comprehensive long-term data regarding its use are available.