Contents
Hyperandrogenism is a condition that involves the excessive secretion of androgens in women. It is characterized by the weakening of the features typical of mature menstruating women with the simultaneous appearance of symptoms of masculinization (male features) and metabolic changes. Androgens are mainly responsible for the development of male sexual characteristics and reproductive organs.
Hyperandrogenism – definition
Hyperandrogenism is the excessive secretion of androgens in women, manifested by defeminization, i.e. weakening of the features typical of mature menstruating women, with a simultaneous increase in masculinization symptoms and metabolic changes. In girls in the period before the first menstruation (menarche), hyperandrogenism may be one of the hallmarks of precocious puberty (pubertas praecox).
Symptoms of defeminization
1) menstrual disorders associated with the disappearance of cyclic changes in gonadotropin secretion, leading to anovulation;
2) disappearance of secondary sexual characteristics (mammary glands and the distribution of adipose tissue typical of women).
Symptoms of masculinization (virilization)
1) excessive body hair in a male type – hirsutism,
2) skin lesions with seborrhea,
3) acne,
4) male pattern baldness,
5) increase in muscle mass with a change in body shape,
6) dark keratosis (acanthosis nigricans) that may suggest insulin resistance accompanying masculinization,
7) clitoral hypertrophy (clitoridomegaly),
8) lowering the tone of the voice,
9) mental changes (depressive syndromes),
10) increase or decrease in libido.
These changes may be accompanied by disorders typical of the metabolic syndrome, i.e. hyperinsulinism resulting from insulin resistance, where the maintenance of normal blood glucose levels requires more insulin synthesis through the islets of the pancreas. In the later stages, the risk of impaired glucose tolerance and the development of type 2 diabetes increases. Moreover, lipid disorders (typically elevated triglycerides and decreased concentration of high-density lipoproteins (HDL) and obesity (especially of the central type) occur.
ANDROGEN METABOLISM IN WOMEN
The androgens present in the serum of women are steroid hormones; they come from the ovary, adrenal glands and the peripheral conversion from proandrogens. Androgens are steroids that can bind the androgen receptor, and the resulting androgen-receptor complex is biologically active. The main androgens present in the blood of women are:
- testosterone,
- dihydrotestosteron (DHT),
- androstendion,
- dehydroepiandrosteron (DHEA),
- Dehydroepiandrosterone Sulfate (DHEAS).
Table 16.1 shows their relative androgenic activity, serum concentrations, and source of origin. The most important androgen in healthy women is testosterone, mainly because of its potency and relatively high concentration. In healthy premenopausal women, approximately 50% of the blood testosterone comes from the peripheral conversion of androstenedione and to a lesser extent. DHEA. The remaining 50% is secreted in approximately the same proportions by the ovaries and adrenal glands. Under the influence of the enzyme 5? –alpha -reductase in many tissues sensitive to the action of androgens, such as hair follicles and sebaceous glands, there is a conversion of testosterone to DHT. The mechanism of hirsutism and acne formation is shown in Figure 16.1.
Dig. 16.1. The mechanism of hirsutism and acne in hyperandrogenism; GnRH gonadoliberin; PCOS, polycystic ovary syndrome; LH – lutropin; FSH – follitropin; 3′-beta-HSD – 3′-beta-hydroxysteroid dehydrogenase; 17? -HSD. 17β-beta-hydroxysteroid dehydrogenase; T – testosterone; DHT – dihydrotestosterone.
Histurism and acne
Hirsutism and acne often coexist in the same patient, but they do not have to occur simultaneously or they appear in different intensities. This is because while both conditions are androgen dependent, certain parts of the hair follicle may show differential sensitivity to testosterone and DHT. With the dominant sensitivity to DHEA, there is a greater tendency to develop acne, while with the predominant sensitivity to testosterone – a greater tendency to develop hirsutism. Activity changes 5? –alpha-reductases may affect the androgenic activity of testosterone. Activity 5? –alpha-reductase is the resultant of the action of two isoenzymes. 5 identified? –alpha-type 1 and type 2 reductase S. are two different enzymes encoded by two different genes located on two different chromosomes. Activity 5 was found in hair follicles and genital skin? –alpha– type 2 reductase, the activity of 5 is predominant in the sebaceous glands? –alpha-type 1 reductase.
Androstendion – unlike testosterone and DHT – it comes primarily from the adrenal glands and ovaries. It is a relatively weak androgen, with 10-20% biological activity compared to that of testosterone, but it can be converted to testosterone and DHT in androgen-sensitive target tissues. Thus, increased production and secretion of androstenedione may play a significant role in the development of hirsutism.
Dehydroepiandrosterone and its sulphate (DHEAS) – they are poorly acting androgens with low biological activity. The main source of DHEA and DHEAS are the adrenal glands. Circulating 17-hydroxysteroids are primarily (80%) bound to sex hormone binding globulin (SHBG), 20% are loosely bound to albumin and only 1-2% remain free or biologically active. SHBG is a universal globulin and has the ability to bind various sex hormones, but the affinity for it is not the same. If the testosterone binding capacity is taken as 100%, the analogous value for estrogens is 30%, and for DHT – 250%. The concentration of SHBG increases under the influence of estrogens and decreases under the influence of androgens. As a result, more than 70% of women with hirsutism have increased levels of free testosterone, although only 40% have an increase in total testosterone levels. The normal concentration of total testosterone, often found in patients with elevated levels of free testosterone, results from the decrease in SHBG levels due to testosterone.
The causes of hyparandrogenism
The definition of hyperandrogenism is based on laboratory evidence of elevated serum levels of androgens and their precursors. Functional hyperandrogenism is diagnosed only when there is no organic cause responsible for the overproduction of androgens. Disorders may concern the ovaries – functional ovarian hyperandrogenism (FOH), adrenal glands – functional adrenal hyperandrogenism (FAH), and less frequent peripheral conversion of estrogens to androgens (e.g. in adipose tissue in obese people). On the basis of additional hormonal and imaging tests, it is often possible to detect the overlap between ovarian and adrenal type of hyperandrogenism. The causes of hyperandrogenism are presented in Table 16.2, and the incidence of hirsutism according to Rittmaster, depending on the causes – in Table 16.3.
Source: A. Cajdler-Łuba, S. Mikosiński, A. Sobieszczańska-Jabłońska, I. Nadel, I. Salata, A. Lewiński: “FUNCTIONAL DIAGNOSTICS OF HORMONAL DISORDERS WITH ELEMENTS OF DIFFERENTIAL DIAGNOSTICS; Czelej Publishing House