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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.

Hyperandrogenism and hypoandrogenism are complex disorders involving multiple-organ systems. While androgen excess is a well-characterized condition, androgen deficiency still needs diagnostic criteria, as there are no specific cutoffs. We highlight the most recent findings on the role of androgens in female pathophysiology, investigating clinically relevant conditions of androgen insufficiency or excess throughout a woman's life, and their possible therapeutic management. Combined oral contraceptives (COCs) should be considered as first-line therapy for the management of menstrual irregularity and/or clinical hyperandrogenism in adolescents with a clear diagnosis of polycystic ovary syndrome (PCOS). There are limited evidence-based data regarding specific types or doses of COCs for management of PCOS in women; however, the lowest effective estrogen dose should be considered for treatment. Despite evidence regarding safety, efficacy, and clinical use, testosterone therapy has not been approved for women by most regulatory agencies for treatment of hypoactive sexual desire disorder (HSDD). The long-term safety for treatments with testosterone is still to be evaluated, and this review highlights the need for more research in this area. [ABSTRACT FROM AUTHOR]

Introduction: Following a historical overview, the ovulation-inhibiting effect of various orally administered estrogen-progestin combinations (combined oral contraceptives [COCs]) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Inhibition of ovulation with progestins alone; estrogens alone; various progestins in combination with ethinyl estradiol; various progestins in combination with natural estrogens (estradiol, estradiol valerate, and estetrol). Expert commentary: The original idea to achieve ovulation blockage through the administration of steroid hormones involved the use a progestogen (both progesterone and its synthetic homologous). The ability of a progestin to inhibit ovulation depends on the type of compound and on its dosage and a difference of more than 20-fold in activity exists between compounds utilized today in COCs. Initially, the estrogenic component was present only because it contaminated the first progestin utilized. It was soon found that an estrogen is necessary for proper cycle control. It was also found that the estrogen acts synergistically in inhibiting ovulation. For almost half a century, most COCs contained ethinyl estradiol. Today, also natural estrogens are being employed. Inhibition of ovulation was complete with all early high dose preparations. Decreasing dosage allowed some ovarian activity to occur, occasionally leading to a mature follicle. Even in this situation, defective corpus luteum formation assured contraceptive protection. [ABSTRACT FROM AUTHOR]

Introduction: The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range. [ABSTRACT FROM PUBLISHER]