A Brief History Of Hormone Replacement Therapy

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Due to today’s longer life spans, women can expect to spend a third of their life — or more — in their postmenopausal years.

While the women of yesteryear were forced to “grin and bear it” when it came to hot flashes, night sweats, irritability, and mood swings, the arrival of hormone replacement therapy (HRT) in the 1960s liberated millions of women from “l’enfer des femmes” (a woman’s hell). 

The Early Promise of Estrogen

In 1966, Robert A. Wilson, M.D.’s book, Feminine Forever, informed women that “menopause is completely preventable” and advised them to take estrogen. The promise of remaining “feminine forever” was met with enthusiasm, and synthetic estrogen became the standard therapy for women undergoing “the change.”

When it later became obvious that estrogen encourages the growth of the uterine lining, which could increase the risk of cancer, the medical community suggested progesterone to protect the uterus. But rather than combine natural, bioidentical progesterone (which is identical to the progesterone produced in the body) with estrogen, pharmaceutical companies added progestin, a synthetic form of progesterone that was patentable. 

Synthetic Hormones Hit the Scene

As a result, Prempro was born. It combined synthetic progesterone (progestin) with Premarin, a drug composed of three estrogens (estrone, equilin, and equilenin) that are derived from horse urine. These horse estrogens (also called CEE) are natural but not bioidentical to those found in the human body.

While the drugs relieved menopausal symptoms for millions of women, the long-term effects were unknown. That changed in 2002  when the results of the Women’s Health Initiative (WHI) came out.

The study, which included over 16,000 postmenopausal women, found the combination of non-bioidentical estrogen and progestin to significantly increase the risk of breast cancer and heart attack.1 It also found an increased risk of stroke in non-bioidentical estrogen users.2

Here is a summary of other findings:

  • The risk of dying from breast cancer almost doubled among Prempro users in comparison to those taking a placebo. 
  • Among those taking estrogen plus progestin, the death rate from breast cancer almost doubled in comparison with the placebo group.3
  • Overall, there was a 25 percent increase in the risk of invasive breast cancer in non-bioidentical HRT users.
  • The use of CEE was associated with a reduced risk of hip fractures. 
  • Estrogen/progestin users had a reduced risk of hip fracture and colorectal cancer in comparison with users of a placebo. 

Because of these study results, female hormone replacement therapy became a sinking ship that women began abandoning in droves. However, the WHI’s findings have recently been called into question. 

Bioidentical Hormones Are a Safer Option

Bioidentical hormones, which have the same molecular structure as the hormones produced in the body, have actually been shown to have a protective effect against some diseases, including those whose risk is increased by non-bioidentical hormones. 

In a study, women who used non-bioidentical estrogen and progestin had a 69% greater risk of developing invasive breast cancer over an eight-year period in comparison with non-HRT users. Those who used bioidentical estrogen and progesterone experienced a similar risk as non-HRT users.4 


1. JAMA. 2002 Jul 17;288(3):321-33.
2. JAMA. 2004 Apr 14;291(14):1701-12.
3. JAMA 2010; 304(15):1684–1692.
4. Breast Cancer Res Treat. 2008 Jan;107(1):103-11.

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