Hormones for women: The benefits of progesterone, the problems with progestin (Provera®)

Hormone replacement therapy can be beneficial. Progesterone is a hormone the female body makes and needs for many health reasons. However, synthetic chemicals (progestins like Provera®) do not have the same benefits. It is vital that women and practicing physicians understand that bio-identical progesterone boosts wellness, and progestins are risky.

Progesterone’s Health Benefits

In women, the hormone estrogen stimulates growth of tissue inside the uterus. To keep the body from producing uterine overgrowth, the hormone progesterone slows this activity and boosts growth elsewhere. (It helps strengthen bone, for example.) Progesterone restricts estrogen synthesis and suppresses the enzymes that promote estrogen production. It blocks estrogen receptors and suppresses the genes that are encoded to promote estrogen production.1

Woman discussing the benefits of progesterone with her doctorWe also know that progesterone is beneficially active upon breast tissue. In fact, progesterone reduces estrogen’s stimulation of breast cancer growth. This was described by the authority in modern gynecological endocrinology, Dr. Leon Speroff, who noted, “Evidence indicates that with increasing duration of exposure, progesterone can limit breast epithelial growth as it does with endometrial epithelium… Human breast tissue specimens removed after patients were treated with estradiol and progesterone indicate that progesterone inhibits in vivo [living humans] estradiol induced proliferation.” 2

Breast Cancer Risk

What’s more, the studies all show that while progesterone lowers breast cancer risk, progestins (synthetic forms of progesterone) do not. It is vital to know the difference between these two if you are considering progesterone hormone supplementation. The alleged “experts” from the American College of Gynecology love to denigrate “so-called” bio-identical progesterone while promoting the use of synthetic progestins.

This doesn’t account for the fact that synthetic progestins promote breast cancer and heart disease, while progesterone beneficially lowers breast cancer and heart disease risk.

Startling Studies

The Women’s Health Initiative reported some startling information in 2002. It revealed that even though some 50 million women had been prescribed synthetic oral estrogen plus progestin therapy for better health (in the belief it would lower heart disease and breast cancer risk) since 1972, it was a mistake.

Prescribing artificial hormones was really an experiment. Nobody knew the long-term effect of these synthetic chemicals. The study reported in the Journal of the American Medical Association (JAMA) showed that Premarin® (a synthetic estrogen) and Provera® (a synthetic progestin) users had increased rates of heart disease and breast cancer, not lower rates.

This study showed that “absolute excess risks per 10,000 person-years attributable to estrogen plus progestin were 7 more CHD events [heart attacks], 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers. The benefits were absolute risk reductions per 10,000 person-years of 6 fewer colorectal cancers and 5 fewer hip fractures.” 3

By the way, the risks attributed to oral estrogen are not at all what we find with bio-identical estrogen when applied transdermally (on the skin). This difference is likely due to the way it is metabolized by the liver.

Hormonal Fear

Women continue to be afraid of progesterone, thinking it is the same as progestin. Don’t be confused here. The Women’s Health Initiative again reported this effect of progestin (not progesterone) in 2009 with a study in the New England Journal of Medicine4 and in 2010 with a study reported in the Journal of the American Medical Association 5 (JAMA) of more than 16,000 postmenopausal women from 40 U.S. clinical centers during 5.9 years. This research showed that progestins plus oral estrogen caused an increase in breast cancer rates. Don’t be alarmed — this was not progesterone that they were using in the study.

Many other studies confirm this distinct difference between progestins (synthetic) and progesterone. Lyytinen, et al. used estrogen and a progestin and found increased breast cancer rates in 3 years.6 The Nurse’s Health Study, which followed 58,000 postmenopausal women for 16 years, found estrogen (oral) alone increased risk for breast cancer by 23 percent, but addition of synthetic progestin resulted in tripling the risk.7

In 2000, Rose, et al. reported a study in which they compared risk for breast cancer between 1,897 postmenopausal women on oral estrogen and synthetic progestin versus 1,637 control women who had never used hormone replacement therapy. They found that progestin increased the risk for breast cancer by 25 percent for every five years of use compared with estrogen alone.8 In addition to these, I have many more such clinical studies I could share with you.

Mistaken Beliefs

You can see that if most physicians and lay people believe progestins to be equivalent to progesterone, they misinterpret these studies to think progesterone is harmful and can promote breast cancer. Progesterone doesn’t do this. Progestins are not the same as progesterone.

So you may wonder if there are clinical studies to prove that progesterone lowers breast cancer. There are eight such studies, each well-designed and with large, impressive numbers to show clear statistical significance.

Better Heart Health

One other important difference between progestins and bio-identical progesterone is their influence on cardiovascular health. Progestins cause potentially harmful vasoconstriction (blood vessels narrow); progesterone stimulates vascular relaxation. Also, lipid profiles (blood fats) are worsened with progestins, but improved with progesterone. There are plenty of studies to show this in the peer-reviewed scientific literature, too.

There are distinct differences between synthetic progestins and real progesterone.

Biochemically, the body does not even make progestins, nor do we know of any enzymes that the body naturally has that can properly metabolize progestins the way it has for progesterone.

Likewise, the enzymes needed to metabolize progesterone properly into either 11-deoxycorticosterone or 17-hydroxyprogesterone requires enzymes that we know the human body has. However, with progestins, we do not know if there are enzymes that will convert it to something safe or to something that is unsafe over time. Once again, this is according to the bible of female hormone metabolism in medical education today, Clinical Gynecologic Endocrinology and Infertility, by Leon Speroff, M.D., and others.

Furthermore, the biochemical structures of several other synthetic progestins have carbon-carbon triple bonds, which are not present in the hormones that humans naturally have. These unnatural synthetic progestins include norethindrone, levonorgestrel and norethindrone acetate.

Hormone Problems

The synthetic hormone problem continues and younger women still receive synthetic progestins for reasons not relating to birth control. Doctors are not acknowledging that the oral contraceptive “pill” (aka OCP) has a link to breast cancer in later years, too. Most studies of OCP and new breast cancers in women before age 40 (the worst ones) show a definite link between cancer and the use of the OCP for long durations. Women who began using the OCP as teenagers (younger than age 20) have a 20 percent relative increased risk for breast cancer. It seems to be related more to the duration of exposure to progestins than the dose for shorter periods of time.9

All of these facts represent information about progestins and progesterone that most doctors don’t know. But with this knowledge, you can look upon bio-identical progesterone very differently than synthetic progestins. In my next article I’ll share the benefits of natural (bio-identical) progesterone and transdermal estrogen (different safety profile than oral estrogen) for you to consider.

To your best health,

Michael Cutler, M.D.
Easy Health Options

1 Speroff L, Glass R, Kase N. Clinical Gynecologic Endocrinology and Infertility. 7th Edition, Lippencott Williams and Wilkins, Baltimore, MD, 2005. p.130.
2 Speroff L, Glass R, Kase N. Clinical Gynecologic Endocrinology and Infertility. 7th Edition, Lippencott Williams and Wilkins, Baltimore, MD, 2005. p.599.
3 “Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women” JAMA. 2002;288(3):321-333.
4 Chlebowski RT, et al. “Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women.” N Engl J Med 2009; 360:573-587.
5 Chlebowski, RT, et al. “Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women.” JAMA. 2010;304(15):1684-1692.
6 Lyytinen H, Pukkala E. et al. “Breast cancer risk in postmenopausal women using estradiol-progestogen therapy.” Obstetrics and Gynecology 2009;113(1):65-73.
7 Colditz GA, Hankinson SE, Hunter DJ, et al. “The use of estrogens and progestins and the risk of breast cancer in postmenopausal women.” N Engl J Med 1995;332(24):1589-1593.
8 Ross RK, Paganini-Hill A, et al. “Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.” J Natl Cancer Inst 2000;92(4):328-332.
9 Speroff L, Glass R, Kase N. Clinical Gynecologic Endocrinology and Infertility. 7th Edition, Lippencott Williams and Wilkins, Baltimore, MD, 2005. p.896.


Dr. Michael Cutler

By Dr. Michael Cutler

Dr. Michael Cutler is a graduate of Tulane University School of Medicine and is a board-certified family physician with more than 20 years of experience. He serves as a medical liaison to alternative and traditional practicing physicians. His practice focuses on an integrative solution to health problems. Dr. Cutler is a sought-after speaker and lecturer on experiencing optimum health through natural medicines and founder of the original Easy Health Options™ newsletter — an advisory on natural healing therapies and nutrients. His current practice is San Diego Integrative Medicine, near San Diego, California.