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Tuesday, October 1, 2013

A better understanding of sex hormones in men

Testosterone is one of the most over-prescribed and poorly understood medications. It is prescribed to millions of men for myriad indications, many of them unproven. Athletes believe it will improve their muscle mass and strength. Older men look to it as an anti-aging remedy. Men with flagging libido hope it will restore their sex drive. Testosterone has developed a mythology of masculinity. This is very similar to the notions we had a generation ago about estrogen being a fountain of femininity before anyone actually studied it.

Part of the difficulty in deciphering the actions of testosterone has been that testosterone is naturally metabolized in men’s bodies to estrogen. The concentration of testosterone in our blood is ten thousand times greater than that of estrogen, but estrogen clearly has important effects in men which are independent of the effects of testosterone. Sorting out which hormone does what has been challenging.

The New England Journal of Medicine (NEJM) published a very cleverly designed study that helps untangle the roles of testosterone and estrogen in middle-aged men.

The study enrolled 400 healthy men between the ages of 20 and 50 who had normal testosterone levels. They all received monthly injections of Zoladex, a medication that shuts off testosterone production in the testes. They were then randomized to 5 different groups. One group applied placebo gel to their skin daily. The next four groups each applied increasing doses of testosterone gel daily, from one quarter the typical testosterone replacement dose to twice the typical dose. That means that these men had their native testosterone production halted, and were replaced with 5 different amounts of testosterone ranging from zero to twice the typical amount.

Half of the men in these five groups were also randomized to receive Arimidex, a medication that blocks conversion of testosterone to estrogen. So these half were deprived of estrogen, regardless of how much testosterone supplement they were receiving. The men receiving Arimidex experienced severe hot flashes from the absence of estrogen.

The men were followed for 16 weeks. They answered questionnaires about their physical function, health status, and sexual function. They did leg presses to measure leg strength. They had CT scans to measure body fat and lean body mass.

By the way, spare a kind thought for the intrepid men who volunteered for such a study. For the reward of only $1,000 and the knowledge that they have served science, they agreed to have their sex hormones altered for 16 weeks. That means the placebo group essentially underwent a temporary castration for the fee of $31.25 per week per testis.

The findings were definitive and surprising. Muscle size and strength were found to be (as expected) due only to testosterone. Estrogen played no role in muscle mass or strength. Interestingly testosterone levels had to get very low before muscle size and strength were affected, suggesting that testosterone supplementation for men with testosterone levels even near the lower limit of normal may not improve their strength. Very little testosterone is all the muscles need.

Body fat turns out to be entirely estrogen dependent, with body fat increasing as estrogen declines. So just as women gain body fat during menopause, men probably gain body fat as their estrogen levels decline with age.

Sexual function was clearly dependent on both testosterone and estrogen. It declined in men deprived of testosterone, but declined even more in men deprived of both hormones.

I know what you’re thinking. “My libido hasn’t been great recently. I should start taking some of my wife’s estrogen supplement.” That’s a terrible idea. The doses your wife takes would likely cause you to grow breasts. Your wife’s reaction to that would likely more than outweigh whatever increase in libido you may experience.

This study doesn’t give us any immediate help in treating patients, but it suggests that checking estrogen levels in men with symptoms of hormone deficiency may be reasonable. And it elucidates which hormones are responsible for which symptoms. The Testosterone Trial is an ongoing study in older men with low testosterone that will help demonstrate the health benefits and harms of testosterone replacement. The results are expected in about a year and will give us much more practical information about who may benefit from treatment.

In the meantime we should remember that masculinity isn’t a molecule. Youth isn’t a medicine. The difference between men and women can’t be prescribed. And even if everyone else is jumping on the latest unproven fad, we are wise to wait for the data. That takes real balls.

Learn more:
Middle-Aged Men, Too, Can Blame Estrogen for That Waistline (New York Times)
Male Sex Drive Depends on Both Estrogen and Testosterone (Bloomberg)
Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men (NEJM article)
Mechanisms of Action of Testosterone — Unraveling a Gordian Knot (NEJM editorial)

Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000. Holding privileges at Cedars-Sinai Medical Center, he is also an assistant clinical professor at UCLA's Department of Medicine. This post originally appeared at his blog.

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Blog log

Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:

Albert Fuchs, MD
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.

And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.

Auscultation
Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.

Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.

Controversies in Hospital Infection Prevention
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Iowa City, IA, with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).

db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.

Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.

DrDialogue
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.

Everything Health
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.

FutureDocs
Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.

Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.

I'm dok
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.

Informatics Professor
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.

David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.

Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.

KevinMD
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.

MD Whistleblower
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.

Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.

Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).

Prescriptions
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.

Reflections of a Grady Doctor
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.

The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.

Technology in (Medical) Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.

Peter A. Lipson, MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.

Other blogs of note:

American Journal of Medicine
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.

Clinical Correlations
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.

Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.

PLoS Blog
The Public Library of Science's open access materials include a blog.

White Coat Rants
One of the most popular anonymous blogs written by an emergency room physician.

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