Estradiol, Testosterone Trigger Dyslipidemia in Women With Complete Androgen Insensitivity

Mitchel L. Zoler, PhD, for Medscape

February 03, 2022

This study was published in as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Patients with complete androgen insensitivity syndrome (CAIS) developed worsened cholesterol profiles when treated with either estradiol or testosterone. Six months on, either agent alone produced significant increases in both total and low-density lipoprotein (LDL) cholesterol and significant decreases in high-density lipoprotein (HDL) cholesterol.

  • Treatment of patients with CAIS with either estradiol or testosterone also led to a small but significant increase in body mass index, although the changes in cholesterol levels appeared independent of weight changes.

Why This Matters

  • This is the first randomized, controlled study to assess in people with CAIS the metabolic effects of two different treatment options for this disorder.

  • The authors say their findings add valuable information to understanding the action of sex steroids on metabolism in people with CAIS.

  • The observed effects on cholesterol levels may be clinically significant because almost half of the patients with normal LDL-cholesterol levels at baseline developed pathological levels after receiving either of the study regimens.

  • The significant associations of estradiol and testosterone treatments and worsening cholesterol levels were unexpected and resemble effects seen in women with hyperandrogenism.

  • The exact mechanisms responsible for the findings have not been determined.

Study Design

  • Three university medical centers and three specialized treatment centers in Germany collectively enrolled 26 women with CAIS who were 18-54 years old during 2011-2016, and overall averaged about 33 years old.

  • Eight subjects dropped out before the investigational phase of the study began.

  • Enrolled patients received either 1.5 mg/day estradiol or 50 mg/day testosterone administered via transdermal patches. Treatment with each drug continued for 6 months, and then patients crossed over to receive the alternative treatment.

Key Results

  • After 6 months on treatment, patients receiving estradiol had an average 10% increase in total cholesterol from baseline, an average 29% increase in LDL, and an average 16% decrease in HDL. After 6 months on testosterone, patients had an average 15% increase in total cholesterol, an average 39% increase in LDL, and an average 16% decrease in HDL. All differences compared with baseline levels were significant.

  • Among 12 patients who had normal levels of LDL cholesterol at baseline, five developed pathological levels on estradiol treatment. All patients had normal levels of HDL cholesterol at treatment onset, and four developed pathologically low levels on estradiol treatment.

  • Among 13 patients with normal LDL cholesterol levels at the start of treatment, four developed pathological levels on testosterone treatment. All patients had normal levels of HDL cholesterol when starting on testosterone treatment, and five had pathologically low levels while on testosterone.

  • Body mass index increased by an average of 2.7% from baseline after 6 months on estradiol, and by an average of 2.8% over baseline after 6 months on testosterone. Both changes were significant, but neither seemed to be the cause of the observed changes in cholesterol levels.

  • The researchers saw no significant changes in blood pressure, hemoglobin, hematocrit, triglycerides, liver parameters, insulin levels, or glucose levels associated with any treatment.


  • The study cohort was relatively small, in part because of relatively high dropout rates and because the study's power analysis was not run for the study's secondary outcomes. This might have resulted in a bias, but the subjects who dropped out of the study did not differ in their baseline characteristics from those who completed the study.

  • The study may have been underpowered to detect more subtle group effects in several measured parameters.

  • Study participants received a fixed dosage of sex steroid delivered transdermally, but because of high variability in transdermal absorption the functional dose each participant received likely differed.

  • The study may have been underpowered to detect more subtle changes in the investigated outcomes.


  • This study received no commercial funding.

  • None of the authors had disclosures.

This is a summary of a preprint research study, "Metabolic Effects of Estradiol Versus Testosterone in Complete Androgen Insensitivity Syndrome," written by researchers located at seven different German centers, on Research Square provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on


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