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UTSW Research: Female sex hormones, adrenal hyperplasia, and more

Studies investigate monthly cycle fluctuations, trial results reducing excess androgens, transcranial magnetic stimulation to treat depression, and liver regeneration

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Sex hormones fluctuate in women taking oral contraceptives

For decades, researchers have assumed that women taking oral contraceptives have stable levels of sex hormones over each monthly cycle. However, a new study in the American Journal of Physiology-Endocrinology and Metabolism led by Yasin Dhaher, Ph.D., Professor of Physical Medicine & Rehabilitation and Orthopaedic Surgery at UT Southwestern Medical Center, shows that the opposite is true.

Using a method called liquid chromatography with tandem mass spectrometry, the researchers tested hormone levels every other day over a 28-day cycle in 16 women who were taking what’s known as combination monophasic oral contraceptives. Results showed that blood concentrations of both exogenous and endogenous sex hormones fluctuated significantly over the cycle. These findings could have significant implications for clinical studies involving women and the potential for more precise and personalized methods of dosing oral contraceptives to reduce unwanted side effects. They also suggest options for the treatment of medical conditions affected by sex hormones, such as musculoskeletal and neurological problems.

Noelle Williams, Ph.D., Professor of Biochemistry; Luis Rodriguez, a Ph.D. candidate in the Joint Biomedical Engineering Graduate Program of UT Dallas and UT Southwestern; and Eric Crossley, B.S., Senior Analytical Chemist, contributed to the study.

Phase 3 trial shows promise for congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of genetic conditions that limit the amount of hormones produced by the adrenal glands, which are the triangular-shaped organs above the kidneys. Without feedback from these hormones, the adrenal glands overproduce androgens such as testosterone. CAH is typically treated with glucocorticoids – synthetic versions of adrenal hormones – often requiring doses far above what the body makes naturally. However, these high doses can cause obesity, insulin resistance, hypertension, decreased bone density, and other side effects.

In results of a phase three clinical trial reported in the New England Journal of Medicine, scientists at 54 centers, including UT Southwestern, tested an experimental drug called crinecerfont, which helps reduce and control excess adrenal androgens through a glucocorticoid-independent mechanism. At the end of the 24-week trial, patients taking crinecerfont were able to reduce their glucocorticoid doses by an average of 27.3%, allowing 62.7% of the group to have levels of adrenal hormones more similar to those produced by healthy individuals. These findings bring crinecerfont closer to U.S. Food and Drug Administration approval.

Oksana Hamidi, D.O., Associate Professor of Internal Medicine in the Division of Endocrinology at UT Southwestern, contributed to the study. Dr. Hamidi also serves as a consultant for Neurocrine Biosciences.

Transcranial magnetic stimulation can improve treatment-resistant depression 

When patients with major depressive disorder (MDD) don’t respond to antidepressant drug treatments, their doctors have several options. They can try a different antidepressant, augment the current antidepressant with an additional drug, or recommend an additional treatment known as transcranial magnetic stimulation (TMS), which uses magnetic fields to stimulate brain cells involved in mood control. Which choice has the best chance of successfully improving treatment-resistant MDD has been unclear. 

To answer that question, UT Southwestern researchers and their colleagues divided a group of 278 patients with treatment-resistant MDD into thirds, assigning each subgroup to one of these three interventions. Their findings, published in Molecular Psychiatry, showed that patients who received augmentation with either TMS or an additional drug experienced significantly greater symptom improvement compared with switching to a different antidepressant for particular measures of MDD symptoms. The researchers suggest that this intervention be considered early in the treatment of MDD patients who don’t improve on an antidepressant alone. 

UTSW researchers Madhukar Trivedi, M.D., Professor of Psychiatry and in the Peter O’Donnell Jr. School of Public HealthManish Jha, M.D., Associate Professor of Psychiatry; and Thomas Carmody, Ph.D., Professor of Public Health and Psychiatry, contributed to this study.

Insights into how the liver heals itself

Unlike most organs, the liver is regenerative, with the capacity to grow new tissue to heal damage. However, the process through which this occurs has been unclear. A team including researchers from UT Southwestern’s Acute Liver Failure Study Group reported in Nature that this process relies on liver cells that migrate to close open wounds before other cells multiply to make new tissue. 

Using samples provided by the study group of human livers damaged by overexposure to acetaminophen or through a type of hepatitis, the researchers identified a population of migratory cells adjacent to wounded areas. These cells produced a protein called ANXA2 that appears to be pivotal to their motion. Using genetic techniques to reduce an analogous protein in mice prevented similar cell migration after liver injury. Additional experiments showed that cell multiplication to make new liver tissue took place after wound closure. These findings eventually could lead to new treatments that facilitate liver healing.

UTSW researchers William M. Lee, M.D., Professor of Internal Medicine, and Jody Rule, Ph.D., Clinical Research Manager with the study group, contributed to the research.

About UT Southwestern Medical Center  

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.