Androgens in Health and Disease.pdf - E Library

Chapter 7/Androgen Excess Disorders in Women 127
even virilization that occurs during pregnancy has its own unique differential, including
benign ovarian sources such as hyperreactio luteinalis (i.e., gestational ovarian theca–
lutein cysts) or luteomas. Even more rare are such fetoplacental sources such as aromatase
deficiency resulting in androgen excess and even virilization in the mother, because of
the placental inability to convert precursor androgens into estrogens.
HIRSUTISM
Mechanisms of Hirsutism
The pilosebaceous unit (PSU) is the common skin structure that gives rise to both hair
follicles and sebaceous glands and are found everywhere on the body except the palms
and soles. The density is greatest on the face and scalp (400–800 glands/cm2 ) and lowest
on the extremities (50 glands/cm2 ). The number of PSUs does not increase after birth
(about 5 million), but they can become more prominent through activation and differentiation.
Before puberty, the body hair is primarily fine, unpigmented, vellus hair. After
puberty and stimulated by the increased androgens, some of these hairs (mainly midline
hair) are transformed into coarser, pigmented, terminal hairs. A similar mechanism may
explain the increase in acne with puberty with increased sebum production by the sebaceous
glands. One of the central paradoxes is that androgens can exert opposite effects (vellus
to terminal, terminal to vellus), depending on the site of the hair follicle (see Fig. 3).
Hirsutism is defined as excess body hair in undesirable locations, and, as such, it is
a subjective phenomenon that makes both diagnosis and treatment difficult. Hirsutism
should be viewed much as polycystic ovaries, as a sign rather than a diagnosis (6). Most
commonly, hirsutism is associated with androgen excess, or what is referred to as androgen-dependent
hirsutism. This tends to be a midline predominant hair growth. It is
important to note that factors other than androgen action may contribute to the development
of hirsutism. Hyperinsulinemia, which accompanies many benign forms of virilization,
can also stimulate the PSU directly, or indirectly by contributing to
hyperandrogenemia. Although insulin resistance is not one of the diagnostic criteria for
PCOS, women with PCOS appear to be uniquely insulin resistant (7). Insulin resistance
in the periphery, primarily skeletal muscle, which utilizes approx 85–90% of circulating
insulin, is compensated for by excess insulin section by the β-cells of the pancreas. The
compensatory hyperinsulinemia may contribute to androgen excess by directly stimulating
androgen production in the adrenal glands and ovaries, as well as suppressing the
production of key binding globulins such as SHBG (with corresponding increased bioactivity
of circulating androgens) or IGF-binding globulins (leading to increased IGF
action in key target tissues such as the ovary). Insulin also has myriad effects on cellular
metabolism, including amino acid and electrolyte transport, stimulating lipogenesis, and
serving as a mitogenic factor. Overall, the net effects are storage of energy in the form
of carbohydrate, protein, and fat.
Differential Diagnosis of Hirsutism
The differential diagnosis of hirsutism includes the disorders of androgen excess
included in the virilization section, but, more commonly, it involves PCOS, NC-CAH,
or idiopathic cases. Idiopathic hirsutism was coined to identify the presence of hirsutism
in a eumenorrheic women with normal circulating androgens, but this may reflect our
limited ability to assess androgen action in the peripheral compartment. When thor-