American College of Physicians: Internal Medicine — Doctors for Adults ®


Annual Session keynote address

The key to understanding gender-based biology

From the May 2001 ACP-ASIM Observer, copyright 2001 by the American College of Physicians-American Society of Internal Medicine.

By Phyllis Maguire

Daniel D. Federman, MACP, claims he learned a valuable lesson during his 45 years of practice in endocrinology: “Never bet against evolution.”

During his keynote speech, “Women’s Health: A Modest (Evolutionary) Proposal,” at Annual Session Opening Ceremony, he explained that the best advice he can give physicians is simple: “Always go back to how evolution set up basic physiology.”

When it comes to gender differences, for instance, evolution made three key decisions, explained Dr. Federman, senior dean for alumni relations and clinical teaching at Harvard Medical School.

First, it gave women and men different reproductive strategies. While women have hormonal and fertility cycles, he said, men are constantly fertile and hormonally acyclic.

The second big evolutionary choice was to use two different sets of hormones—androgens and estrogens—to express sexual differences. Dr. Federman said that a logical route would have been for male genes to produce only androgens and for female genes to produce only estrogens.

“That would have been the purest genesis of women’s health and men’s health as discrete specialties,” Dr. Federman pointed out. Instead, estrogen cannot be produced independently and must be synthesized by androgen. As a result, both hormones are present in both genders.

What distinguishes the genders is the relative predominance of one or the other hormone, Dr. Federman said.

Dr. Federman points out that sexual differences affect every organ and system in the body.

In determining that predominance, evolution opted for two regulatory controls: how much androgen to make and how much androgen to convert to estrogen. Dr. Federman explained that women produce 300 micrograms of androgen a day and convert 50% of it to estrogen, while men produce 7,000 micrograms but convert only a quarter of 1% to estrogen.

The third major evolutionary decision was to not segregate sex hormones to sexual organs and functions, but to spread them throughout the body as somatic hormones.

“Every organ and system in the body has some capacity to respond to sexual differences,” Dr. Federman said, pointing out that sexual hormones play a role in cardiovascular, autoimmune, endocrinological, neurological and musculoskeletal conditions. “Sexual differences are involved in the etiology, pathogenesis and clinical presentation and management of diseases throughout internal medicine.”

Dr. Federman applauded the leaders of women’s health for raising awareness about the role of gender in disease and launching the emerging science of gender-based medicine. However, he went on to propose that internists, regardless of their specialties, learn about the full spectrum of gender-related biology in order to bring the best care to all patients.

“Isn’t providing the best care that is guided by newly emerging science what this specialty is all about?” he asked.


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