Related Topics: Bioidentical Hormones, Breast Cancer, Features

3 Myths About Bioidentical HRT And Cancer Risks

With 5 years now being recommended as the maximum time on conventional HRT it is time to look at some of the reasons to go bioidentical that are backed up by research.

AnnA Rushton

Sorting through the facts relating to hormone replacement can be cumbersome and confusing to patients as well as practitioners.

More than a decade has passed since the halting of the CEE/progestin arm of the Women’s Health Initiative (WHI), and there has been little clarification on the subject from mainstream medical sources. There are however, several glaring misconceptions relating to bioidentical HRT) especially as it relates to cancer risk, which should be cleared up.

1: Mind your ‘P’s: Progestins, progestogens and progesterone

Progestogen or progestin (it is the same thing, just different names in different countries) is a very general name for molecules that have a core structure that is similar to progesterone but are synthetic and have very different actions to the natural hormone. These molecules are most commonly found in contraception and conventional HRT.

Many, many medical sources – including studies published in reputable medical journals will not only use these words interchangeably, but also consider them one and the same.

THIS IS NOT TRUE; it is imperative to read the methods section of these studies, and not just the abstract or the headlines. In the infamous WHI study, where an increased risk of breast cancer and cardiovascular disease was found, the study subjects were being given medroxyprogesterone acetate (a progestin), NOT progesterone.
Unfortunately, the message extrapolated from that study has lead to many reports of progesterone increasing the risk of breast cancer. In studies where progestins and progesterone have been compared head to head the progestins have repeatedly been found to increase breast cell proliferation while progesterone has not.


• Murkes D, Conner P, Leifland et al. Effects of percutaneous estradiol-oral progesterone versus oral conjugated equine estrogens-medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women. Fertil Steril. 2011 Mar 1;95(3): 1188-91.

• Murkes D, Lalitkumar PG, Leifland et al. Percutaneous estradiol/oral micronized progesterone has less-adverse effects and different gene regulations than oral conjugated equine estrogens/medroxyprogesterone acetate in the breasts of healthy women in vivo. Gynecol Endocrinol. 2012 Oct;28 Suppl 2:12-5.

• Fournier A, Berrino F, Riboli E et al. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer. 2005; 114(3): 448-54.

• Chang KJ et al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril. 1995; 63(4):785-91.

• Wood CE, Register TC, Lees CJ et al. Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys. Breast Cancer Res Treat. 2007 Jan;101(2):125-34.

• Campagnoli, C., Abbà, C., Ambroggio, S., & Peris, C. (2005). Pregnancy, progesterone and progestins in relation to breast cancer risk. J Steroid Biochem, 97(5), 441-450.

2: Oral vs. topical progesterone and the endometrium

Historically, one of the primary reasons for including any progestogen in an HRT prescription is to protect the endometrium from uncontrolled growth that may lead to to endometrial or uterine cancer. Even among prescribers who know to recommend progesterone rather than a progestin, there is a common misconception that only oral progesterone will protect the endometrium.

This myth is likely rooted in concern that topical progesterone does not raise serum levels to adequately counteract the proliferative effects of estrogen. When histologic analysis of the endometrium (endometrial biopsy) is used for analysis, both topical and vaginal progesterone provide sufficient protection to the endometrium.


• Stanczyk FZ, Paulson RJ, Roy S. Percutaneous administration of progesterone: blood levels and endometrial protection. Menopause. 2005 Mar;12(3) 232-7.

• Anasti J, Leonetti H, Wilson K. Topical progesterone cream has antiproliferative effect on estrogen-stimulated endometrium. Fertil. Steril. 2003 Jan;79(1):221-2.

• Sendag F, Terek MC, Karadadas N. Sequential combined transdermal and oral postmenopausal hormone replacement therapies: effects on bleeding patterns and endometrial histology. Arch Gynecol Obstet. 2001 Nov;265(4):209-13.

• Leonetti HB, Landes J, Steinberg D, Anasti JN. Transdermal progesterone cream as an alternative progestin in hormone therapy. Altern Ther Health Med. 2005 Nov-Dec, 11(6):36-8.

3: Bioidentical hormones are “natural” and “safe”

Bioidentical simply means that the hormone matches the chemical and molecular structure of hormones that are produced by the human body. These products are typically produced by modifying a compound that comes from soy or yam; however, this conversion does not happen in vivo and must be done in a laboratory. Thus, while the sources of the hormone are natural, and its role in the body is natural, the molecule itself is synthesized.

Oestrogen is a proliferative hormone and a woman’s exposure to it over her lifetime can increase her risk of breast cancer, regardless of whether or not the hormone is produced by her own body, taken in the form of a synthetic oestrogen or administered in a bioidentical form. Similarly, exposure to oestrogen-like compounds such as those found in some plasticizers and pesticides can increase cancer risk.

The relative safety of Bioidentical HRT vs. conventional HRT is due to the combination of hormones given and the importance of prescribing progesterone instead of a progestin (see #1 above).


• Holtorf, K. (2009). The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med, 121(1), 73-85.

• L’hermite M, Simoncini T, Fuller S, Genazzani AR. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. Maturitas. 2008 Jul-Aug;60(3-4):185-201.

• Fournier, A., Berrino, F., & Clavel-Chapelon, F. (2008). Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Tr, 107(1), 103-111.

• Fournier, A., Fabre, A., Mesrine, S., Boutron-Ruault, M.-C., Berrino, F., & Clavel-Chapelon, F. (2008). Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer. J Clin Oncol, 26(8), 1260-1268.

• Markey, C., Luque, E., Munoz-de-Toro, M., Sonnenschein, C., & Soto, A. (2001). In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod, 65, 1215-1223.

• Jobling S, Reynolds T, White R, et al. (1995). A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect, 103:582-587.

Helpful information:

These are just a few of the common misconceptions surrounding hormone replacement, particularly for women with a family history of breast cancer who wrongly believe they can’t use bioidentical hormones. If you are considering using bioidentical HRT then it’s important to have a clear understanding of the pros and cons.

Progesterone is known to be protective of the breast and used and recommended by bioidentical doctors for women with menopausal symptoms and a history of breast cancer treatment and/or risk and who cannot use oestrogen.

This article is reproduced by courtesy of Labrix Clinical Services

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Please feel free to discuss this article in the comments section below, but note that the author cannot respond to queries made there.
Comments 7
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Kathleen | 6:49 pm, February 10th, 2017

this has been very helpful to me i have been on Bio-Identical Hormones Estradiol/Progesterone and Testosterone for 10 years now and just tuned 70 and was wondering if I should be getting off of them but it sounds like the benefits out way any the bad so I guess I will stay on them. Thank You.

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dgqa | 7:56 pm, April 30th, 2014

For women who are post-menopausal, accepting and experiencing the usual symptoms as part of the ageing process, versus any form of hormone replacement, seems to be the safest way to confront their situation. Confronting the many hormonal-disruptors that are present in food and drinks via any form of plastics, food sources subjected to pesticides, herbicides, or growth-hormones, by becoming proactive against their consumption, will go a long way toward achieving hormonal-balance and well being.
Even if all of the above is followed, some sort of detoxification regimen is also of great importance, since air pollution (via utilities and other industries including areas as far away as China, geo-engineered atmospheric spraying, plus vehicular emissions and agricultural spraying) all takes a considerable toll on our bodies, and many of those forms of pollutions play a part in hormonal disrupting for both women and men.

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jr | 5:56 pm, April 30th, 2014

Yes, without progestin/progesterone. :-)

WHI found a similar increase, maybe 2%, but much smaller than in the Prempro arm. I still can’t figure out though why WHI found a slightly lower BC risk in the Premarin-alone arm, despite the fact that breast density, breast pain and abnormal mammograms were all increased. It could just be that Premarin takes a long time to cause breast cancer, ie 10-15 years.

As for TS Wiley/Suzanne Somers, it is beyond me why anyone in the field would ever give them the time of day. The “protocol” is quite dangerous IMHO and probably poses the same risk that the Ortho Evra birth control patch does (more clots and strokes). Pregnancy only lasts 9 months, whereas this regimen probably puts a woman’s body into a state mimicking chronic pregnancy.

All this proves to me is that there really is no such thing as estrogen “deficiency” (or at least not in the U.S. where obesity is rampant), except in rare circumstances where a woman is starving or emaciated.

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Dr. S | 3:37 am, April 30th, 2014

To jr: Wow, thanks for your additional data. I had never seen these details.
Just to make sure I have the data straight: the 1.2% increase in breast density with premarin was _without_ progestin/progesterone?
With pregnancy’s raised clot risks, probably not a good idea to raise estrogen levels to pregnancy levels like The Wiley protocol does, eh?

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jr | 12:19 am, April 30th, 2014

Oral estrogen does incite inflammation and clots, more so than transdermal. But estradiol is a more potent estrogen than estrone. Clinical trials have shown that estradiol without progesterone/progestin caused an increase in breast density by nearly 5% whereas Premarin caused only a 1.2% increase. The recent KEEPS trial also found that women randomized to estradiol vs. Premarin or a placebo had more abnormal mammograms, though this is yet unpublished. Transdermal estradiol, while less harmful in terms of clots and gallbladder disease, leads to higher sustained blood levels than pills do, so this is potentially problematic. Also, let’s not forget that pregnancy (endogenous estrogen) raises clot risk more than pills.

I do agree that progesterone is without a doubt the safest hormone to take under any circumstances. It has benefits that progestin does not (for sleep, sleep apnea, blood pressure and traumatic brain injury) and none of its risk (breast cancer). However, the evidence for a safety and efficacy advantage of estradiol over Premarin is still not supported by randomized trials.

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Dr. S | 4:45 pm, April 29th, 2014

To jr: No, actually Premarin is likely worse since the main estrogen they share with humans is estrone, one of the more inflammatory estrogens. The other estrogens in Premarin don’t naturally occur in humans, so have uncertain effects. Also taking estrogens by mouth leads to more inflammatory metabolites since they are absorbed in the gut and go straight to the liver where they get metabolized before they make it to the rest of the body.
Otherwise, yes.

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jr | 7:10 pm, April 26th, 2014

Definitely agree. Progesterone vs. progestin is probably the only valid pro-BHRT argument. Estrogen is estrogen and any kind has risks. If anything, estradiol is possibly WORSE than Premarin because it is more potent and, especially when delivered transdermally in patch or gel form, causes a sustained elevation in blood levels.

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