Related Topics: Bioidentical Hormones, Features, HRT

Don’t Monkey With My Hormones!

Animal studies are showing that combining bioidientical natural progesterone and estrogen provides a safe form of HRT. Here Dr Dach focuses on why progestins are not the answer and can increase breast cancer risk.

Dr Jeffrey Dach

Hormone Studies from the Primate Center at Winston Salem are quite revealing and allow us to answer questions about different effects of various hormone formulations.

I often quote the 2008 French Cohort Study by Fournier demonstrating safety of bioidentical hormones.  This study showed that bioidentical hormone users in France (using Estradiol and Progesterone) had same breast cancer risk as non-hormone users.  In other words, there was no increased risk of breast cancer with this combination of bioidentical hormones.

Adding MedroxyProgesterone (MPA)

When the added progestin is  Medroxyprogesterone (MPA), there is increased breast cancer risk.  However, there is no increased risk with the addition of progesterone.  Confirmatory findings were seen in the WHI study (First Arm) which also showed increased invasive breast cancer with the combination of Premarin and Medroxyprogesterone   also called Prempro.

Now that we have the 11 year follow-up data of the Second Arm, Premarin-Alone (CEE horse estrogen) study of the Women’s Health Initiative, we can ask some more questions.  The Premarin-Alone Arm showed a 20-27% decrease in breast cancer compared to placebo.

Why Less Cancer with Premarin-Alone, and More with Estradiol Alone?

One might ask the obvious question, “Why is Premarin-Alone associated with decreased breast cancer risk compared to non-hormone users, while Estradiol-alone (bioidentical) is associated with a 29% increase in invasive breast cancer in the French Cohort study?

The answer comes from Dr Wood at the primate center in Winston Salem in a 2008 report using Macaque monkeys. They compared Premarin and Estradiol in a monkey model, and found a highly significant 259-330% increase in breast cell proliferation in Estradiol treated monkeys compared to controls. The Premarin treated monkeys however, had far less cell proliferation, only 75% was noted using the KI-67 antigen test of cell proliferation.

This difference in cell proliferation, indicating a stonger estrogenic effect with Estradiol, explains why estradiol alone  is associated with increased breast cancer risk, while Premarin   is not.  Premarin has less proliferative effect on breast tissue than does Estradiol as demonstrated in monkeys, and in the differing breast cancer rates in human studies.

Why It’s Important to Add Progesterone

So this underscores the importance of adding progesterone to an estradiol-alone regimen. Post-menopausal women given an estrogen-alone regimen because of prior hysterectomy may be at increased risk of breast cancer and would do better to either add progesterone to their program, or switch to a bioidentical Estrogen/Progesterone combination.  We preferentially use a combined cream to make sure both hormones are taken together in the proper ratio to prevent endometrial hyperplasia and reduce breast proliferation.  We also make sure every hormone-user takes Iodine supplements, which are breast cancer preventive.

Protective Effects of Progesterone Compared with Harmful Effects of Medroxyprogesterone – Breast Cell Proliferation

Another question we might ask is:

“How can we explain why Medroxyprogesterone  causes increased breast cancer, while (bioidentical) progesterone does not”

Dr. Wood published a primate hormone study in 2007 in which Medroxyprogesterone (MPA) was compared to Progesterone, finding Estradiol plus Medroxyprogesterone (MPA) significantly increased breast cell proliferation using Ki67 markers.  However,  Estradiol with Progesterone did not increase cellular proliferation.    Previous primate studies by Cline in 1998 showed the same increased breast cell proliferation with addition of Medroxyprogesterone   to Premarin treated monkeys.

Dr Cline’s conclusion:

“These findings indicate that progestogens  may exacerbate, not antagonize mammary gland proliferation induced by estrogen (Premarin) replacement therapy

This protective effect of Progesterone (bioidentical) was confirmed in two double blind human studies by Chang and Foidart in which addition of Progesterone reduced the proliferative effects of estrogen, thereby explaining its cancer preventive effect.(19,20)  Breast proliferation is the underlying factor in increasing cancer risk.  Inhibiting breast proliferation prevents breast cancer.


Armed with this information about Estriol, we can now confidently say that the a combination with Progesterone is the safest HRT regimen one can possibly devise.

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician.  More information on Jeffrey Dach and his work at his website:

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