Estrogen-Only Hrt

A recent study in Lancet Oncology looking at data from the Women’s Health Initiative (WHI) reported that the use of estrogen (Premarin) alone was NOT associated with an increased risk of breast cancer and the use of estrogen-progestin (Prempro) increased the risk of breast cancer.

At first glance this may seem contradictory since estrogen has been traditionally associated with increased breast cancer.  Here’s a possible explanation.  The Million Women Study in England and the French E3N cohort study have reported that the timing for when estrogen is first started after menopause is a critical factor in determining breast cancer risk.  Women who started estrogen in the first 3-5 years after menopause had a higher risk of breast cancer than those starting estrogen AFTER 5 years. So starting estrogen more than 5 years after onset of menopause is considered a long gap time while starting estrogen immediately after menopause is considered a short gap time.

This is a complex issue so let me first give you some background to make it easier to understand. Most invasive breast cancers are the end result of a decades long evolution of increasingly abnormal premalignant cells. Estrogen is thought to promote breast cancer NOT by causing new cancer cells but rather by accelerating the growth of small, premalignant cells so they become detectable on clinical exam or mammogram. When breast tissue is deprived of estrogen at menopause for many years, it causes shrinkage of these premalignant cells.

Correlating this to the WHI study, recall that the WHI participants who were started on Premarin had been menopausal on NO estrogen for an average of 8 years.  Some of them were 20 years post menopause and had NEVER taken estrogen!  So you would expect to see less breast cancer because after so many years of being without estrogen whatever premalignant cells they had would have died off.  So that’s exactly what was seen with women in WHI.

Now if we’re postulating the TIMING as an explanation, why would you see increased breast cancer risk with the combination hormone pill called Prempro?  By the way, this increased risk of breast cancer with combined synthetic estrogen/progestin is a consistent finding in many studies.  A possible mechanism could be the addition of a daily progestin like the Provera found in Prempro that turns off apoptosis, a protective mechanism of the body that destroys early cancer cells. Another study reported another harmful effect of a daily progestin:  increased productions of RANKL, a protein molecule that stimulates breast cells to multiply and not die when they should.

So what does a woman do who’s considering HRT? Does she have to suffer miserably from hot flashes for 5 years to decrease her risk of breast cancer and then start estrogen?  Does she have a hysterectomy so she doesn’t have to worry about taking a progestin??  ABSOLUTELY NOT!!  First of all by depriving yourself of estrogen for 5 years, not only are you likely to be having the typical low estrogen symptoms like hot flashes but you’re also subjecting yourself to an increased risk of heart disease, osteoporosis, Alzheimer’s, sexual dysfunction and a poor quality of life!

The French E3N study in 53,000 women reported that women who took estrogen + progesterone had NO increased risk of breast cancer when they started HRT within 3 years of menopause.  So the take-home message from these studies is to avoid synthetic progestins and opt for natural hormones like estradiol and progesterone.  You can avoid the increased heart attacks and strokes seen in WHI by choosing topical estrogen in the form of patches, gels, creams and mists that are available at any drug store. It’s important for women to know that these pharmaceutical natural hormones (also called bioidentical hormones) are superior to compounded bioidentical hormones because they are required to meet higher standards for quality control and efficacy.

Women need to know there’s a window of opportunity of 10 years from menopause when they will get the most protection from estrogen against heart disease, osteoporosis and Alzheimer’s.

The majority of women who go through menopause, get the classic symptoms: hot flashes, night sweats, insomnia, anxiety, depression, sexual dysfunction, and brain fog. For those who still have their uterus, menopause is easier to recognize because their periods stop. When a young woman in her 30’s or 40’s has a hysterectomy and has her ovaries removed, she will likely have severe symptoms.  However, for those women who have had a hysterectomy and still have their ovaries, the loss of estrogen may occur so gradually they don’t notice it.  Some of the subtle signs associated with estrogen loss can be:  weight gain especially around the waistline, crying spells for no reason, not being able to multi-task, dry skin, PMS, acne and sexual dysfunction.  Women are often treated with antidepressants and other drugs.  These are all symptoms that often resolve with estrogen therapy so it’s important for women to recognize this so they can ask their physicians about considering HRT.

This information is all explained in detail in my book, “Outliving Your Ovaries.“ My book is based on my review of 450 medical journal articles and supported by 30 years of clinical experience.  I wrote the book to give women a guidebook to sort out the confusion about HRT so they can better participate with their physicians in selecting the best HRT for themselves.




1. Anderson GL, Chlebowski RT, Aragaki AK et al, “Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial,” The Lancet Oncology, Early Online Publication, 7 March 2012, doi;10,1016/S1470-2045(12)70075-X

2. Fournier A, Mesrine A, Boutron-Ruault MC, et al, “Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?” Journal of Clinical Oncology 27: 5138-5143.

3. Leslie Bernstein, “Combined Hormone Therapy at Menopause and Breast Cancer: A Warning—Short-Term Use Increases Risk,” Journal of Clinical Oncology 27: 5116-7


4. Fournier, A, Berrino, F, and Clavel-Chapelon, F, “Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study,” Breast Cancer Research and Treatment, vol 107, no. 1 (2008): pp 1033-1111.


5. Ory K, Lebeau L, Levalois C, et al, “Apoptosis inhibition mediated by medroxyprogesterone acetate treatment of breast cancer cancer,” Breast Cancer Research and Treatment, vol. 68 (2001): pp 187-198.

6. Schramek D, Leibbrandt A, Sigl V, et al, “Osteoclast differentiation factor RANK controls development of progestin driven mammary cancer,” Nature, published online 9/29/10doi:10.1038/nature09387.

7. Beral V, Reeves G , Bull D, and Green J for the Million Women Study Collaborators,
“Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy,” Journal of the National Cancer Institute 2011;103:296–305


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