Do Estrogens Cause Cancer?

As Published in TG Forum
and Transgender Community News

Estrogens are the most ubiquitous hormones in the female body and the most sought after by the MTF community. But recently their safety as orally administered preparations have been called into question with recent studies showing cancer producing propensities. The National Institutes of Health this month included Estrogen Therapy in its 10th annual list of potential carcinogens. So the best we can do is understand just what they are and carefully weigh the risks and benefits. My conclusion is that the benefits far outweigh the risks involved, both physically and theoretically. Estrogen derived from the Greek "Oistros, meaning mad desire" and "gennan, to produce" is the generic term for a family of hormones produced naturally in the female and synthetically by the pharmaceutical companies. Six of the top 100 selling prescription drugs are products containing ethinyl estradiol or conjugated equine estrogens. They are marketed for contraception or hormone replacement therapy (HRT). A new preparation, Cenestin is synthetically derived from the plant sterols of Soy and Yam. It contains nine weaker estrogens and it’s effectiveness has not been demonstrated beyond a 3 month study. It is marketed primarily as alternative HRT. Estrogens (Es) belong to the steroid class of hormones derived from Cholesterol and are naturally produced by the ovaries, adrenals and by peripheral fat in the breasts. Es include estradiol-E2, estrone-E1, estriol-E3 and progesterone. 17 beta Estradiol is produced by the ovary in the largest quantity and has the highest affinity for estrogen receptors in the breasts and female reproductive organs. Oral Es are first conjugated in the liver to inactive estrone and estriol, which have diminished potency, but then are excreted into the intestines where they are converted to active Es and reabsorbed into the circulation. This first pass effect stimulates the liver to improve your cholesterol and HDL lipid profile, but also produces binding proteins which carry the active hormones in the bloodstream to the receptors.

Both males and females have estrogens and androgens competing in a delicate balance for these receptors. The amount and time that the hormone is bound to the receptor will determine the tissue response. Two types of estrogen receptors, alpha and beta, have been identified in both males and females. The ovary, uterus, breast and cardiovascular system contain both types. The importance of Es in stimulating breast cell growth and in increasing the risk, albeit small, of breast cancer is well established.

Androgens, male hormones, are thought to inhibit breast development independent of your genetic sex. Pubertal Estradiol rise causes breast development in girls and frequently in boys. In MTFs oral Estrogen therapy stimulates full acinar and lobular breast growth and is indistinguishable under the microscope from female mammary tissue. Supporting the inhibitory role of androgens is the fact that approximately 50% of men on the androgen receptor blocker, Bicalutamide, develop breast enlargement. Conversely androgen use by FTMs leads to breast atrophy with time. Recent experimental data suggest that HRT upsets the normal E-androgen balance in women and promotes unopposed estrogen stimulation of breast tissue increasing the potential for breast cancer. In the normal breast, estrogen stimulates the ductal system and lobular tissue is dependent on progesterone. Therefore MTF feminizing therapy consists of a synthetic estrogen administered either orally or with a Transdermal patch and a progestational agent as MPA, medroxyprogesterone acetate, to stimulate breast development.

Since the only valid studies relating to Breast Cancer and HRT are done in post-menopausal women whose hormonal state is closest to the MTF TS, we must look to these studies for advice. Approximately 60 studies and 5 meta analyses of these studies have produced conflicting evidence in this area. The chance of a post menopausal 50 year old women developing breast cancer on HRT for 10 years is approximately less than 1% greater than if she was not taking HRT. In the most recent study of the Women’s Health Initiative, the increased absolute excess risk over 5 years was 8 additional breast cancers per 10,000 person years. The absolute risk to an individual was very small. This figure is less than one-tenth percent per year. This study only evaluated Prempro, conjugated Es and MPA, and may be different with other Es alone. Nevertheless, this was considered significant and the study with Prempro was stopped. The Transdermal estrogen-progesterone patch, which avoids the liver, appears to be the most physiologic way to deliver these hormones at this time. While the evidence for cardiovascular improvement has disappeared due to the small increased risk of blood clots, stroke and heart attack in the first year of HRT, the improvement in colon cancer risk and osteoporosis still stands. Skin and hair texture improves as well mental functioning. Breast cancer has been reported in the MTF TS, but at no greater incidence than that observed in untreated males, which is exceedingly rare.

So in conclusion, Estrogens give us the opportunity to change what we want at a very small risk. We can still use all the other preventive measures against cardiovascular heart disease that are afforded the general population as we realize that HRT is not the "Prevention Panacea" once proclaimed.

Best Wishes in Your New Future,
Cerise Richards, M.D.