Are Bioidentical Hormones Safe?
In 2009 Kent Holtorf, MD published a paper in Postgraduate Medicine to answer the question are bioidentical hormones safe and efficacious? He reviewed nearly 200 studies that focused on clinical efficacy, physiologic actions of hormones on breast tissue, and the risks of hormones on breast cancer and cardiovascular disease comparing the differences between bioidentical and non-bioidentical hormones in these three areas.
We will summarize some of Dr. Holtorf’s paper here, but encourage you to read his paper for yourself.
Bioidentical hormones have unique, and in some cases, opposite physiologic effects on tissue than non-bioidentical hormones. We highlighted some of those opposite effects in our previous article Pharmaceutical Companies and Non-bioidentical hormones when we compared the effects of bioidentical progesterone to medroxyprogesterone acetate (MPA).
Progesterone versus MPA
In comparison to non-bioidentical MPA, bioidentical progesterone showed greater efficacy, higher patient satisfaction, and better quality of life in Dr. Holtorf’s literature review.
Bioidentical progesterone was associated with a 30% reduction in sleep problems, 50% reduction in anxiety, 60% reduction in depression, 30% reduction in somatic symptoms, 25% reduction in menstrual bleeding, 40% reduction in cognitive problems, and a 30% improvement in sexual function in comparison to MPA.
Breast Tissue Effects of Progesterone versus MPA
Bioidentical progesterone is antiproliferative and anti-carcinogenic effects on the breast. Synthetic MPA has pro-carcinogenic (tumor producing) effects on breast tissue.There at least 3 different progesterone receptors in breast tissue: PRA, PRB, and PRC. In healthy breast tissue the ratio of PRA:PRB is 1:1. Breast cancer cells have an altered ratio of PRA:PRB. Synthetic progestins like MPA alter that ratio providing a mechanism for increased risk of breast cancer in MPA users.
Also, synthetic progestins increase the conversion of weaker estrogens into more potent estrogens possibly increasing breast cancer risk as well. Progesterone does not have this effect on estrogen. Progesterone downregulates estrogen-receptor-1 and induces breast cancer cell apoptosis (programmed cell death of cancer cells). Thus, bioidentical progesterone protects against breast cancer and studies show lower risk of breast cancer in women receiving bioidentical progesterone compared to women receiving synthetic progestins.
Progestins and Heart Disease
As we’ve already discussed in the second article in this series it was progestin that was responsible for the increase in heart attacks seen in the Women’s Health Initiative (WHI). Progestins alter a women’s cardiovascular risk profile by increasing body weight, increasing blood pressure, raising the bad LDL cholesterol and lowering the good HDL cholesterol, and negate the beneficial effects of estrogen on the heart. Progestins also cause vasoconstriction and spasm of coronary arteries predisposing to heart attacks.
Estriol and Breast Cancer Risk
There are two estrogen receptors on tissues: estrogen receptor-alpha (ER-α) and estrogen receptor-beta (ER-β). ER-α promotes breast cell proliferation or growth while ER-β inhibits proliferation and prevents breast cancer development. So when it comes to breast cancer ER-α is bad and ER-β is good.
There are three main estrogens: estrone (E1), estradiol (E2), and estriol (E3).
Estradiol activates both ER-α and ER-β equally and thus has a neutral effect of breast cancer. Estrone activates ER-α at a 5:1 ratio. Estriol which is a weak estrogen but it activates ER-β at a ratio of 3:1. So when it comes to lowering the risk of breast cancer estriol is good and estrone is bad. Guess which hormone is dominant in post-menopausal women? Estrone. Therefore, estriol should be considered in post-menopausal women to offset the adverse effects of estrone. But, it is too weak an estrogen to provide other health benefits and should be given with estradiol.
Progestins downregulate (decrease) ER-β – another mechanism by which synthetic progestins raise breast cancer risk. Premarin and other conjugated estrogens (non-bioidentical) also downregulate ER-β.
Pregnancy is associated with dramatic increases in progesterone and estriol and postpartum continue to produce higher levels of progesterone and estriol in comparison to women who never been pregnant. Women who have pregnant have lower rates of breast cancer than women never pregnant.
HRT and Blood Clots
Conjugated estrogens are associate with higher rates of venous thrombosis or blood clots. Transdermal bioidentical estrogens and bioidentical progesterone are not. One study showed a four-fold increase in blood clots in women on synthetic progestins.
Are Bioidentical Hormones Safe?
The reason most women seek HRT is for symptomatic relief from post-menopausal symptoms. And, in that regard non-bioidentical and bioidentical hormones are both effective, but bioidentical hormones have a safer risk profile. One thing should be clear from this discussion and our previous articles. Synthetic progestins should be avoided by women interested in receiving HRT. Most of the negative effects from HRT that women have heard over the years are related to synthetic progestins, though conjugated estrogens (Premarin) are associated with higher risks of stroke and blood clots while having a neutral on cardiovascular health (WHI study).