Revisiting the physiological role of androgens in women

ABSTRACT

Introduction

Extensive research underlines the critical functions of androgens in females. Nevertheless, the precise mechanisms of their action are poorly understood. Here, we review the existing literature regarding the physiological role of androgens in women throughout life.

Areas covered

Several studies show that androgen receptors (ARs) are broadly expressed in numerous female tissues. They are essential for many physiological processes, including reproductive, sexual, cardiovascular, bone, muscle, and brain health. They are also involved in adipose tissue and liver function. Androgen levels change with the menstrual cycle and decrease in the first decades of life, independently of menopause.

Expert opinion

To date, studies are limited by including small numbers of women, the difficulty of dosing androgens, and their cyclical variations. In particular, whether androgens play any significant role in regulating the establishment of pregnancy is poorly understood. The neural functions of ARs have also been investigated less thoroughly, although it is expressed at high levels in brain structures. Moreover, the mechanism underlying the decline of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with age is unclear. Other factors, including estrogen’s effect on adrenal androgen production, reciprocal regulation of ARs, and non-classical effects of androgens, remain to be determined.

KEYWORDS:

• Androgens
• female physiology
• fertility
• hormones regulation
• reproduction

Article highlights

• Despite being the most abundant sex hormones in women, the potential role and precise mechanism of action of androgens in women is poorly understood

• The significant factors that contribute to this ‘knowledge gap’ include a) the difficulty of dosing androgens with standard laboratory methods, b) the difficulty of taking into account the diurnal and cyclical variations in androgen levels for blood sampling, and c) the uncertainty of what is considered normal in serum androgen levels in women of different ages

• Several studies show that androgen receptors (ARs) are broadly expressed in several female tissues (urogenital tissue, mammary gland, nervous systems, bone, cardiovascular system, adipose tissue, and liver), where they mediate crucial functions and, until recently, were thought to be only targets of estrogen

• Androgen levels change with the menstrual cycle and decrease in the first decades of life, independently of menopause

• Amongst the mechanisms that need further investigation, is the potential role of androgens in regulating pregnancy. Another topic to investigate is the function of AR in several structures of the CNS involved in cognitive processes. Furthermore, the molecular mechanisms behind decreasing DHEA and DHEAS levels with advancing age are also unclear

• Other factors, including estrogen’s effect on adrenal androgen production, reciprocal regulation of ARs, and non-classical effects of androgens, remain to be determined

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.