High testosterone, dihydrotestosterone linked to adverse metabolic phenotype in patients with PCOS

Patients with polycystic ovary syndrome who have a high testosterone to dihydrotestosterone ratio appear to be more likely to have an adverse metabolic phenotype, according to recent findings.

In the study, researchers evaluated 275 premenopausal women aged 16 to 48 years with PCOS and 35 BMI-matched, premenopausal, health women aged 21 to 50 years as controls. The researchers recorded anthropometric data for all participants, including height, weight, waist circumference and hip circumference.

Researchers recorded systolic and diastolic blood pressure measurements and calculated BMI. Fasting blood samples were taken to evaluate basal hormone serum levels. Additionally, an oral glucose tolerance test was performed, and blood samples were collected at 30, 60 and 120 minutes to determine glucose and insulin concentrations.

A routine method for liquid chromatography/mass spectrometry was used to determine total testosterone (T), total dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA).

The researchers found that patients with PCOS had significantly higher levels of total T (P<.001), free testosterone (P<.001) and free DHT (P<.001) vs. healthy controls. Additionally, patients with PCOS had a significantly higher total T/DHT ratio (P<.001). No difference was found between PCOS and control participants in terms of total DHT levels (P=.072).

An analysis of just patients with PCOS revealed a significantly higher total T/DHT ratio in patients with obesity (P<.001) as well as those with metabolic syndrome (P<.001), impaired glucose tolerance (P<.001) or insulin resistance (P<.001).

The researchers also found significant association between total T/DHT ratio and various adverse anthropometric, hormonal, lipid and liver measures, and measures of glucose tolerance.

“This correlation was only found in PCOS patients, suggesting the [total] T/DHT ratio is a new biomarker for an adverse metabolic phenotype in PCOS patients,” the researchers wrote. “Nevertheless, future studies and larger trials are needed for the evaluation of results.”

PCOS increased risk for CVD, obesity.

In a case-control study, researchers found that young women with polycystic ovary syndrome have a higher prevalence of cardiovascular disease risk factors, including hypertension, obesity and metabolic syndrome, compared with controls. The researchers also found significantly lower levels of lipoprotein apolipoprotein A-I and observed a significant reduction in efflux capacity.

  • “Given the available data, there is evidence to suggest that women with PCOS are at an increased risk for developing CV-related outcomes,” Andrea Roe, MD, of the department of obstetrics and gynecology in the division of reproductive endocrinology at the University of Pennsylvania, and colleagues wrote. “These data strongly support educating all PCOS patients about the associated risk of dyslipidemia and need for frequent lipid screening.”

The researchers evaluated women aged 18 to 50 years with PCOS (n=124) and geographically matched controls (n=67). The patients with PCOSdemonstrated higher BMI and blood pressure, but similar HDL and LDL levels compared with controls, according to data.

The mean ApoA-I levels were lower and ApoB to ApoA-I ratio was greater among patients with PCOS compared with controls (P<.01), researchers wrote.

In addition, women with PCOS displayed an 11% decrease in normalized cholesterol efflux capacity compared with controls (P<.05). The cholesterolefflux capacity was correlated with BMI, ApoA-I, HDL and presence of metabolic syndrome, researchers wrote.

Multivariable regression model data indicated that PCOS was significantly associated with less cholesterol efflux (beta level, –0.05; 95% CI, –0.1 to –0.009).

After adjustments for age and BMI, PCOS was also significantly associated with an atherogenic profile, including an increase in large VLDL particles, size and small LDL particles (P<.01).