High androgen levels up risk of hypertension in women

Excess androgen in women is associated with increases in blood pressure (BP), claims an expert who presented several studies at the recent Kidney Week 2019 of the American Society of Nephrology.

Dr Licy Yanes Cardozo from the Departments of Cell and Molecular Biology and Medicine/Endocrinology at the University of Mississippi Medical Center shared two cases in which high levels of androgen correlated with elevated BP.

The first case was of a 30-year-old woman diagnosed with polycystic ovary syndrome (PCOS). On her physical exam, she had a BP of 140/90 mm Hg and a body mass index (BMI) of 38 kg/m². Her laboratory test revealed high levels of free (1.57 ng/dL) and total testosterone (120 ng/dL).

“PCOS is recognized as the most common endocrine disorder that affects reproductive age women,” said Yanes Cardozo. “One of the cardinal features of these women is that they can present with elevated levels of androgen.”

Moreover, PCOS is the leading cause of infertility in young women, but women with this condition also have a cluster of cardiovascular risk factors such as elevated BP, Yanes Cardozo added. Of note, up to 40 percent of those with PCOS will have increases in BP.

An epidemiological study by Chen and colleagues showed that characteristic hyperandrogenaemia in young women with PCOS was associated with an elevated BP, independent of age, insulin resistance, obesity or dyslipidaemia. [Hypertension 2007;49:1442-1447]

To prove causation, Yanes Cardozo and her team characterized the metabolic and cardiovascular-renal consequences of hyperandrogenaemia in a female rat model that mimics many of the changes occurring in women with PCOS.

Results showed that hyperandrogenaemic female (HAF) rats demonstrated increases in food intake, body weight, BP and glomerular filtration rate. HAF rats also had insulin resistance with increases in nonfasting glucose and insulin levels, as well as abnormal oral glucose tolerance test. Furthermore, these rats exhibited factors associated with the metabolic syndrome, such as elevations in leptin, cholesterol, peri-renal fat weight and tumour necrosis factor-α. [Gend Med 2011;8:103-115]

In the PCOS model, angiotensin converting enzyme (ACE) inhibitors eliminated androgen-induced obesity and BP, according to Yanes Cardozo, noting however that ACE inhibition did not modify androgen-induced insulin resistance.

Another study in which Yanes Cardozo was a part of highlighted the importance of early detection and treatment of hyperandrogenaemia “to prevent the cardiometabolic derangements found in patients with PCOS… because once cardiometabolic dysregulations have been established, normalization of the androgenic profile may have little beneficial effect.” [J Endocr Soc 2018;2:949-964]

“In clinical scenarios characterized by hyperandrogenaemia in women, prompt normalization of androgen levels may be necessary to prevent their long-lasting cardiometabolic effects,” Yanes Cardozo said.

In her second case, a 41-year-old biological female who identified himself as a male was seeking gender reassignment therapy with testosterone. On physical examination, the transgender patient had a BP of 150/94 mm Hg and a BMI of 41 kg/m².

Two months after administration of testosterone cypionate injections, his free (5.7 ng/dL) and total testosterone levels (540 ng/dL) reached the normal range of those in biological men (free: 4.26–16.4 ng/dL; total: 280–950 ng/dL). However, his BP (160/94 mm Hg) and BMI (51 kg/m²) increased even further despite being counselled about the side effects of testosterone in women.

This finding was consistent with that of a 2018 study, in which testosterone therapy led to an increase in systolic and diastolic BP, as well as an increase in low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol, in transgender men. [Rev Endocr Metab Disord 2018;19:243-251]

Of note, there have been “no clinical trials or long-term prospective studies in the effect of sex steroids and cardiovascular diseases in transgenders,” according to Yanes Cardozo.

In the management of excess androgen, Yanes Cardozo said that the combination of glucagon-like peptide type 1 receptor agonists and ACE inhibitors “could be a promising therapeutic tool to treat hyperandrogenaemia-induced cardiometabolic complications.” [Endocrinology 2019;160:2787-2799]