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Articles on HRT & Synthetic Hormones

Safety and Efficacy of Bioidentical Hormones Versus
Synthetic Hormone Replacement Therapy


Clinical studies compared bioidentical and nonbioidentical hormones focusing on 3 key areas 1) clinical efficacy,
2) physiologic actions on breast tissue, and 3) risks for breast cancer and cardiovascular disease.



1)     Symptomatic Efficacy of Synthetic Progestin versus Progesterone

Four studies of patients using HRT, including either progesterone or synthetic progestins, compared efficacy, patient satisfaction, and quality of life. Women in all 4 studies reported greater satisfaction, fewer side effects and improved quality of life when they were switched from synthetic progestins to progesterone replacement.


The effect of progesterone compared to synthetic progestins included a 30% reduction in sleep problems, a 50% reduction in anxiety, a 60% reduction in depression, a 30% reduction in somatic symptoms, a 25% reduction in menstrual bleeding, a 40% reduction in cognitive difficulties, and a 30% improvement in sexual function. Overall, 65% of women felt that hormone replacement with progesterone was better hormone replacement with synthetic progestins.


2)     Differing Physiological Effects of Bioidentical Progesterone and Synthetic Progestins

Studies compared the physiological differences in breast tissue of those on progesterone with those on synthetic progestins found that synthetic progestins can significantly increase estrogen-stimulated breast cell mitotic activity and proliferation. In contrast, progesterone inhibits estrogen-stimulated breast epithelial cells. Natural Progesterone is breast protective. Synthetic Progesterone can raise breast cancer risk.

3)     Breast Cancer and Cardiovascular Disease Risks


Risk for Breast Cancer with Synthetic Progestins: The Women’s Health Initiative (WHI), a large randomized clinical trial, revealed that synthetic progestins significantly increase the risk for breast cancer.
The Nurses’ Health Study followed 58,000 postmenopausal women for 16 years and found that, compared with women who never used hormones, use of synthetic estrogen from ages 50-60 years increased the risk for breast cancer by the age of 70 by 23%. The addition of synthetic progestin to the estrogen replacement resulted in a tripling of the risk for breast cancer (67% increased risk).


Risk for Breast Cancer with Bioidentical Progesterone: Studies have consistently shown a decreased risk for breast cancer with progesterone. Chang et al examined the effects of estrogen and progesterone on women prior to breast surgery in a double-blind, placebo-controlled study in which patients were given placebo estrogen or placebo transdermal progesterone. Others were given actual estrogen or transdermal progesterone for 10-13 days before breast surgery. Estrogen increased cell proliferation rates by 230% and progesterone decreased cell proliferation rates by 400%. Women with low progesterone have significantly worse breast cancer survival rates than those with more optimal progesterone levels.


Estriol and the Risk for Breast Cancer:  Estriol is less likely to induce proliferative changes in breast tissue compared to other estrogens. There fore estriol has been associated with a reduced risk of breast cancer. Estriol and progesterone levels dramatically increase during pregnancy. This increased exposure to progesterone and estriol during and after pregnancy confers a significant long-term reduction in the risk for breast cancer. If these substances were cancer-causing, it would be expected that pregnancy would increase the risk for breast cancer rather than protect against it. And this is not the case.

Cardiovascular Risk with Synthetic Progestins versus Progesterone:

Synthetic progestins produce negative cardiovascular effects and negative cardio-protective effects of estrogen. Bioidentical Progesterone, in contrast, has the opposite effect because it maintains and augments the cardio-protective effects of estrogen, thus decreasing the risk for heart attack and stroke. Synthetic progestins negate the positive lipid effects of estrogen and show a consistent reduction in HDL, the most important readily measured determinant of cardio-protection, while bioidentical progesterone maintains and augments estrogen’s positive lipid and HDL effects.

As a side note: synthetic progestins can significantly increase insulin resistance, when compared with bioidentical estrogen and progesterone use.  This is why so many women gain weight on synthetic hormones.


Bioidentical hormones have been associated with lower risks of breast cancer and cardiovascular disease, and are more efficacious than their synthetic counterparts. Bio-identical hormones remain the safest method of hormone replacement.




© Postgraduate Medicine, Volume 121, Issue 1, January 2009