Trans Women May Require Higher Doses of Estrogens Interview with:

Joshua Safer, MD, Executive DirectorCenter for Transgender Medicine and SurgeryMount Sinai Health SystemSenior Faculty, Medicine, Endocrinology, Diabetes and Bone DiseaseIcahn School of Medicine at Mount Sinai

Dr. Safer

Joshua Safer, MD, Executive Director
Center for Transgender Medicine and Surgery
Mount Sinai Health System
Senior Faculty, Medicine, Endocrinology, Diabetes and Bone Disease
Icahn School of Medicine at Mount Sinai What is the background for this study? What are the main findings?

Response: The standard trans feminizing hormone regimen includes estrogen both to suppress testosterone and so that the individual has sufficient circulating sex hormone in the body for good bone health. After orchiectomy, there is no need to suppress testosterone because the levels are very low and it is common to cut the estrogen dose in half.  Cis women with premature ovarian failure often take about 2 mg of estradiol daily so that dose has seemed reasonable for trans women without testes.  However, when my co-author Sira Korpaisarn and I checked estradiol levels and gonadotropins (pituitary hormones, LH and FSH) as a guide to dosing, we found that based on that testing, trans women may require higher doses of estrogens than the 2 mg that we expected.

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Estrogen Patch in Newly Postmenopausal Women May Reduce Alzheimer’s Risk Interview with:

Kejal Kantarci, M.D. M.S. Professor of Radiology Division of Neuroradiology

Dr. Kejal Kantarci

Kejal Kantarci, M.D. M.S.
Professor of Radiology
Division of Neuroradiology What is the background for this study? What are the main findings?

Response: A rapid decline in estrogen with menopause may be associated with an increased risk of Alzheimer’s disease risk in women. This study was conducted in newly postmenopausal women who received 17β-Estradiol via a skin patch or conjugated equine estrogen orally or placebo.

Those who received 17β-Estradiol patch had reduced β-amyloid deposits, the plaques found in the brains of people with Alzheimer’s disease, three years after the end of the hormone therapies.

In the study, women with APOE e4 — one form of the most common gene associated with late-onset Alzheimer’s disease — who received the 17β-Estradiol patch had lower levels of β-amyloid deposits than those who received placebo.

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Estrogen Therapy In Young Women May Not Increase Breast Cancer Risk

Dr. Clarice R. Weinberg Ph.D Biostatistics and Computational Biology Branch National Institute of Environmental Health Sciences Research Triangle Park, NC Interview with:
Dr. Clarice R. Weinberg Ph.D
Biostatistics and Computational Biology Branch
National Institute of Environmental Health Sciences
Research Triangle Park, NC 27709

MedicalResearch: What is the background for this study?

Dr. Weinberg: Hormone therapy (HT) was commonly prescribed in the U.S. late in the 20th century to help women through the challenges of menopause. Several decades ago, therapy with estrogen alone was shown to cause endometrial cancer, and the combined use of both estrogen and progesterone replaced treatment with estrogen alone. But research published around 2002 had far reaching effects on gynecologic practice. Both the randomized trial component of the US Women’s Health Initiative and the observational European Million Women’s Study reported that postmenopausal women who were older than 50 and were taking the combination HT had an increased risk of breast cancer. Physicians and patients responded quickly, and Hormone therapy use plummeted.

However, it remained unclear whether there were risks of Hormone therapy use in women under age 50. Some factors, for example obesity, have opposite effects on the risk of breast cancer in pre- and post-menopausal women, so one cannot assume risk findings from older women necessarily apply to younger women. We carried out a sibling-based study of 1,419 women with breast cancer diagnosed under the age of 50 ( Each case had a sister (also studied) who had never been diagnosed with breast cancer, who could serve as her control. The study was funded by Susan G. Komen for the Cure, and the National Institutes of Health.

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Estrogen Effects on Metabolism & Weight Gain in Women Studied

It’s no secret that women often gain weight as they get older. The sex hormone estrogen has an important, if underappreciated, role to play in those burgeoning waistlines.

Now, researchers reporting in the October Cell Metabolism, a Cell Press publication, have traced those hormonal effects on metabolism to different parts of the brain. The findings may lead to the development of highly selective hormone replacement therapies that could be used to combat obesity or infertility in women without the risks for heart disease and breast cancer, the researchers say.

“When women approach menopause, they gain weight in fat and their energy expenditure goes down,” says Deborah Clegg of the University of Texas Southwestern Medical Center. Estrogen levels decline and women grow increasingly susceptible to obesity and metabolic syndrome.

Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone’s influence on metabolism, Clegg suspected receptors in the brain.

Others had traced the effects of estrogen on energy balance specifically to estrogen receptor-α (ERα). When her team deleted those receptors from the entire brains of mice, “we got very, very fat mice,” Clegg said. The animals consumed more calories and burned less.

The researchers showed female mice lacking ERα in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERα from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERα receptors in those same neurons also led to various problems in ovulation and fertility.

The findings suggest that drugs developed to specifically target estrogen receptors in the brain might offer a useful alternative to hormone replacement therapies that hit receptors throughout the body. The researchers say they would like to continue to isolate other estrogen-related effects and symptoms, for instance, on hot flashes and cognition.

“The more we know about estrogen’s sites of action, the more likely it is we could develop designer hormone replacement therapies targeting tissue X, Y or Z,” Clegg said.