Midlife and Menopause

A Brief History of Hormone Treatment

The two primary sex hormones found in a woman’s body are estrogen and progesterone. Testosterone also naturally occurs in women’s bodies. “Hormone therapy” is the term that has been used to describe certain drugs that are prescribed to women at menopause. It can refer to the use of estrogen alone or to a combination of estrogen and a progestogen or a combination of estrogen and an androgen (a form of testosterone). (The term progestogen refers to a class of substances that includes the natural progesterone in our bodies and synthetic progestins used in hormone treatment.)

Until very recently, this treatment was called “hormone replacement therapy,” but the word “replacement” has been dropped. Hormone treatment never literally raised postmenopausal women’s hormones to premenopausal levels. Also, medical research has shown that taking estrogen after menopause will not replace the function that estrogen played in the body before menopause and is not necessary for optimal health. Indeed, it confers risk of harm. The concept of estrogen replacement was a clever marketing idea that was never backed up by good evidence. Because the term therapy is usually used in medicine when there is a disease or condition that requires therapy and the menopause transition is a normal physiological process, this chapter will use the more neutral term “hormone treatment” instead of “hormone therapy.”

Estrogen has been used since the 1930s to treat hot flashes and other physical changes that women experience at menopause. But starting in the 1960s, the list of reasons that women were advised to take hormones began to grow. In 1966, the book Feminine Forever became a best seller with its claim that “menopause is completely preventable.”¹ The book’s author, Robert A. Wilson, wrote that because the estrogen level in a woman’s body dropped after menopause, postmenopausal women who didn’t receive treatment were no longer truly female. Wilson traveled the country, lecturing on this topic and promising that with the help of estrogen therapy, “Every woman alive today has the option to remain feminine forever.” But soon after, reporters at The New Republic and The Washington Post disclosed that Dr. Wilson’s lecture tour and work were being supported by a company that manufactured estrogen for hormone treatment.² When this issue was raised again in 2002 by Wilson’s own son, the company responded that it could not confirm the account because it was so far in the past and the company had no record of any such financial arrangement.³

During the decades that followed, drug companies promoted and doctors prescribed hormones to women to prevent and treat an increasingly broad range of ailments and experiences associated with aging, from wrinkles and general aches and pains to Alzheimer’s disease, depression, and heart attack. The FDA had initially approved hormone treatment for hot flashes and other problems associated with menopause, not for disease prevention. However, in the late 1980s and the 1990s, several observational studies suggested that hormone treatment might improve women’s quality of life and, most significant, protect women against heart disease. In 1986, the FDA reviewed the evidence and found that hormone treatment was effective for treatment of osteoporosis. In 1990, the FDA found that the research done to date was not adequate to support adding heart disease prevention to the list of approved uses. But doctors are allowed to prescribe drugs for uses that are not approved by the FDA. Encouraged by the research suggesting that hormone treatment might be helpful for new uses, as well as by extensive drug company marketing efforts, many health care providers did just that. Such off-label prescribing is common practice in medicine when research to support new claims has not been completed, though in many cases it means that people are taking drugs that haven’t been adequately proven to be safe or effective for the purposes for which they are being used.

Some women’s health advocates became concerned that using hormone treatment might actually be harmful to women’s health. A few had raised warning flags as early as the 1950s,⁴ and the concern grew more intense in the mid-1970s when two studies linked estrogen to endometrial cancer.⁵ But researchers soon discovered that adding a progestogen to estrogen (“combined treatment”) reduced this risk. After that, doctors began prescribing combined hormone treatment to women who still had a uterus and thus were at risk of endometrial cancer, while women who had undergone hysterectomy continued to take estrogen alone.

In 1977, Barbara Seaman’s book Women and the Crisis in Sex Hormones alerted women to evidence that taking hormones could cause breast cancer, strokes, and blood clots and warned against the overpromotion of hormones for the treatment of menopause.⁶ Like Feminine Forever, Seaman’s book became a best seller, educating a generation of women about the health risks of hormones. But the effort to sell hormone treatment as a pill to make you healthy, happy, and beautiful continued unabated, supported by multimillion-dollar advertising campaigns. Against a background of seemingly conflicting data, with some research suggesting benefits and other studies indicating dangers,⁷ hormone treatment soon became the most prescribed drug in the country.*

The first major study to challenge the theory that hormone treatment was beneficial for heart disease was the HERS study, published in 1998, which found that women with heart disease who used hormone treatment had worse outcomes than those who didn’t take hormones.⁸ But hormone treatment proponents discounted the HERS results, saying that they didn’t apply to healthy women. The widespread use of hormone treatment did not change significantly until 2002, when a large-scale research study of hormone treatment known as the Women’s Health Initiative (WHI) revealed evidence that taking hormones did not protect healthy women against heart disease and stroke. In fact, the first publicly released results of the WHI showed that women who took the combination of estrogen and progestin had increased their risk for breast cancer, stroke, heart attack, and blood clots. This led to a swift and significant drop in the number of hormone prescriptions worldwide, as many women stopped taking hormones. Some women later resumed hormone treatment because they were experiencing hot flashes or other menopausal changes that they found problematic, but research has shown that about half the women who stopped taking hormones did not have that problem.⁹

* This overprescription of hormones based on an incomplete and preliminary understanding of their effects underscores the problem with relying on observational studies to guide medical practice. (For more information on different types of research studies, see page 23.) The observational studies of hormone treatment found an association between hormone treatment and lower levels of heart disease, but this type of study cannot prove that a treatment prevents a disease. Still, pharmaceutical companies promoted this sort of evidence, which supported a larger market for their products.

End of excerpt
Excerpted from Chapter 7: Hormone Treatment in Our Bodies, Ourselves: Menopause  © 2006 Boston Women's Health Book Collective

2. Gary Null and Barbara Seaman, "Wilson Versus Living Decay," For Women Only! Your Guide to Health Empowerment (New York: Seven Stories Press, 1999), 751. [back to text]

3. Gina Kolata and Melody Peterson, "Hormone Replacement Study: A Shock to the Medical System," New York Times (July 10, 2002): A1; see also Amanda Spake, Susan Headden, Katy Kelly, The U.S. New library staff, and Nancy Cohen, "The Menopausal Marketplace," U.S. News & World Report 133, no. 19 (November 18, 2002):42. [back to text]

4. Madeline Gray, The Changing Years: What to Do about the Menopause, 1951, cited in Barbara Seaman, The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth (New York: Hyperion, 2003), 110. [back to text]

5. D. C. Smith, R. Prentice, D. J. Thompson, and W. L. Herrmann, "Association of Exogenous Estrogen and Endometrial Carcinoma," New England Journal of Medicine 293, no. 23 (December, 1975):1164-67; H. K. Ziel and W. D. Finkle, " Increased Risk of Endometrial Carcinoma among Users of Conjugated Estrogens," New England Journal of Medicine 293, no. 23 (December 1975):1167-70; T. M. Mack, M. C. Pike, B. E. Henderson, R. I. Pfeffer, V. R. Gerkins, M. Arthur, and S. E. Brown, "Estrogens and Endometrial Cancer in a Retirement Community," New England Journal of Medicine 294, no. 23 (June 1976):1262-67. [back to text]

6. Barbara Seaman and Gideon Seaman, Women and the Crisis in Sex Hormones  (New York: Bantam, 1977). [back to text]

7. Nancy Kreiger, Ilana Löwy, Robert Aronowitz, Judyann Bigby, Kay Dickersin, Elizabeth Garner, Jean-Paul Gaudillière, Caroline Hinestrosa, Ruth Hobbard, Paula A. Johnson, Stacey A. Missmer, Judy Norsigian, Cynthia Pearson, Charles E. Rosenberg, Lynn Rosenberg, Barbara G. Rosenkrantz, Barbara Seaman, Carlos Sonnenschien, Ana M. Soto, Joe Thornton, George Weisz, "Hormone Replacement Therapy, Cancer, Controversies, and Women's Health: Historical, Epidemiological, Biological, Clinical and Advocacy Perspectives," Journal of Epidemiology and Community Health, 59 (August 2005): 740-48. [back to text]

8. Stephen Hulley, Deborah Grady, Trudy Bush, Curt Furberg, David Herrington, Betty Riggs, Eric Vittinghoff, for the Heart and Estrogen/Progestin Replacement Study (HERS) Research Group, "Randomized Trial of Estrogen plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women," JAMA 280, no. 7 (August 1998):605-13. [back to text]

9. Judith K. Ockene, David H. Barad, Barbara B. Cochrane, Joseph C. Larson, Margery Gass, Sylvia Wassertheil-Smoller, JoAnn E. Manson, Vanessa M. Barnabei, Dorothy S. Lane, Robert G. Bryski, Milagros C. Rosal,  Judy Wylie-Rosett, and Jennifer Hays, "Symptom Experience after Discontinuing Use of Estrogen + Progetin," JAMA 294, no. 2 (July 2005):183-93. [back to text]

Excerpted from Our Bodies, Ourselves: Menopause, © 2006, Boston Women's Health Book Collective.