Causes and treatment of acne: a gynecologist's view

In the pathogenesis of acne, one of the main links is genetically determined hyperandrogenism, which can be either absolute (increased levels of androgens in the blood) or relative (increased sensitivity of skin receptors to normal or reduced levels of androgens in the body).

Androgens stimulate the hair follicle and sebum production. An increase in the synthesis of androgens in the body leads to hirsutism (increased hair growth) and blockage of the follicle with subsequent infection. These changes in the synthesis of sex steroids are accompanied by disturbances in the menstrual cycle, which can manifest as delayed menstruation (oligomenorrhea) or uterine bleeding. In addition, increased production of androgens can contribute to infertility in women.

Testosterone and dihydrotestosterone, the most active androgens, play a special role in the development of hyperandrogenic conditions. The source of androgens in a woman’s body are the ovaries, adrenal cortex and peripheral tissues. Therefore, the occurrence of acne due to hormonal imbalance is promoted by diseases such as polycystic ovary syndrome (PCOS), tumors of the uterus and ovaries, endometriosis, hypothyroidism, and obesity.

PCOS in 65–72% of cases is combined with insulin resistance (IR). It has been proven that IR in women with PCOS is caused by a defect in the post-receptor region of insulin binding sites. After insulin binds to the receptor, autophosphorylation of the tyrosine base of the intracytoplasmic part of the receptor occurs, and subsequently of other intracellular substrates. In PCOS, along with tyrosine phosphorylation, serine phosphorylation occurs, which leads to inhibition of intracellular processes and disruption of the enzymatic properties of cytochrome P450c17. The latter is a key enzyme in the biosynthesis of androgens in the ovaries and adrenal glands. With its participation, androstenediol, testosterone, and dihydroepiandrostenediol (DEHA) are synthesized [6, 7, 9]. In the skin, under the influence of 5α-reductase, it is converted into the most active androgen - dihydrotestosterone, which stimulates the hair follicle and sebum production. This leads to hirsutism and blockage of the follicle with subsequent infection.

Pathology of carbohydrate metabolism

Patients with excess body weight require special attention from any doctor, since they need to exclude metabolic syndrome. This pathology is characterized by a violation of carbohydrate and lipid metabolism. That is, it is accompanied by an increase in insulin, glucose, cholesterol and high-density lipoproteins. Hyperinsulinemia promotes increased synthesis of androgens, which not only increase sebum synthesis and the risk of menstrual irregularities, but also increase appetite, acting on the hunger center in the brain. Thus, in women with excess body weight, a vicious circle closes (insulin - androgens - increased appetite - insulin).

IR can be suspected in women with overweight and the android type of obesity. The severity of obesity is determined using the body mass index (BMI), which is calculated as the ratio of body weight in kilograms to the square of height in meters. The ideal BMI value is less than 25 (18.5–24.5), overweight is considered to be a BMI of 25–29.9, class I obesity is a BMI over 30, class II obesity (moderate) is a BMI of about 35, obesity III degree (pronounced) – with a BMI of 35–40 [8]. The type of obesity is determined by the ratio of waist circumference to hip circumference (WC/HC). The value of this index less than 0.85 indicates the female (gynoid, lower, gluteofemoral) type of obesity. With a WC/TB ratio > 0.85, the distribution of adipose tissue is of the male (visceral, upper, android, Cushingoid) type [8].

IR can be determined by the HOMA (Homeostasis Models Assessment) index, to calculate which the basal concentrations of glucose and insulin are multiplied and divided by 22.5. If the obtained indicators are more than 2.7, then the presence of IR is confirmed [8].

For such patients, along with drug treatment, a balanced diet is recommended. It is believed that reducing body weight against the background of a reduction diet leads to the normalization of not only carbohydrate and fat metabolism, but also to a decrease in androgens and restoration of ovulation. The diet involves reducing the total calorie content of food to 2,000 kcal per day, of which 30% comes from carbohydrates, 40% from proteins and 30% from fats, and saturated fats should account for no more than 1/3 of the total amount of fat [1, 3, 6, 8].

IR treatment is carried out simultaneously with the diet. Drugs that increase the sensitivity of peripheral tissues to insulin include biguanides (metformin). The mechanism of their action is associated with the ability of the drug to inhibit gluconeogenesis, increase the sensitivity of peripheral receptors to insulin and stimulate the uptake of glucose by muscle cells. The drug is prescribed at a dose of 1,000–1,500 mg per day, taken for 3–6 months under the control of a glucose tolerance test or the HOMA index [1, 6]. It is interesting to note that metformin is part of a group of drugs used to treat hirsutism in PCOS. In 2003, Harborne L. et al. a comparative analysis proved the effectiveness of this insulin sensitizer in the treatment of hyperandrogenism. The effect of metformin at a dose of 1,500 mg per day was comparable to the well-known antiandrogenic drug Diane-35, and its use at a dose of 1,000 mg per day had the same antiandrogenic effect as Veroshpiron 50 mg per day [6, 8] .

To treat insulin resistance, thiazolidones (pioglitazone, rosoglitazone) are also used, which enhance the expression of the GLUT-4 gene, which is the main glucose transporter in muscle and fat tissues. Thiazolidinediones also increase insulin-dependent suppression of hepatic glucose production, which reduces the concentration of glucose circulating in the blood. These drugs are prescribed for 6–9 months at a dosage of 15–30 mg per day under the control of the HOMA index [6, 8].

COC therapy

To achieve the best effect, gynecologists most often combine the use of insulin sensitizers with combined oral contraceptives (COCs). Women with acne are shown drugs that contain progestogens with an antiandrogenic effect (cyproterone acetate, dienogest, chlormadinone acetate, desogestrel, drospirenone) [1, 2, 4]. Patients for whom COCs are contraindicated are prescribed antiandrogens such as cyproterone acetate, spiroloctone, 5α-reductase blockers or glucocorticoids. These medications can block androgen receptors and 5-reductase. The action of COCs is aimed at reducing the synthesis of androgens by the ovaries by suppressing the function of the hypothalamic-pituitary system (decreased FSH, LH). Oral contraceptives contain ethenyl estradiol, which increases the synthesis of sexsteroid-binding globulin (SSBG). With an increase in the amount of CVD, the level of active testosterone in the blood decreases [6, 8].

The choice of one or another antiandrogen depends not only on the hormonal status of the woman, but also on the presence of concomitant diseases. For example, in patients with diabetes mellitus, coronary heart disease, atherosclerosis, varicose veins, or with a history of heart attack, stroke or thromboembolism, COCs are contraindicated. Therefore, the selection of antiandrogenic drugs is always individual.

In the practice of a gynecologist-endocrinologist, idiopathic hyperandrogenism is sometimes encountered. It is accompanied by the absence of disturbances in ovulatory function and polycystic changes in the ovaries. Circulating androgen levels are often within normal limits, and metabolic disturbances are absent or minimal. In this case, an increase in 5α-reductase in the blood serum is very often observed [6]. For women with idiopathic hyperandrogenism, COCs with antiandrogenic activity or 5α-reductase blockers can be recommended.

It is also necessary to remember about oncopathology, which may be accompanied by hyperandrogenism. Diagnosing tumors of the ovaries or adrenal glands in the modern world is easy; just do an ultrasound examination. If a tumor of the reproductive system is confirmed, these patients are referred to oncologists.

Hyperandrogenism as a consequence of diseases of other organs and systems

The liver plays a special role in the inactivation of hormones. Hepatocytes synthesize sexsteroid-binding globulin, which, by binding to androgens, converts them from the active form to the inactive one [1, 2]. With hepatitis, liver cirrhosis, parasitic liver damage and intoxication, the synthesis of this protein decreases, which leads to an increase in free androgen fractions.

It is important to study the function of the thyroid gland. With hypothyroidism, the synthesis of thyroid-stimulating hormone increases, which helps reduce the production of SSSH in the liver, and consequently, increase the free fractions of androgens.

Hyperandrogenism may be a consequence of a pituitary tumor. Unfortunately, these patients may not always have neurological symptoms, but in 80–95% of cases they are accompanied by oligo- or amenorrhea. Verification of this diagnosis is carried out after studying prolactin in the blood serum and MRI of the brain [2].

In addition, patients with acne should be examined for urogenital infections - trichomonas, ureaplasma, mycoplasma and chlamydia. These infections can also cause similar changes to the skin. If a sexually transmitted infection is detected, treatment is necessary together with the sexual partner. Otherwise, there will be no effect from the treatment.

Thus, in addition to consulting a dermatologist, women with acne should visit a gynecologist, who will definitely prescribe a hormonal examination and ultrasound of the pelvic organs. The range of examination and treatment is selected individually for each patient.

Literature:

1. Almazov V. A., Blagoslovskaya Ya. V., Shlyakhto E. V. Insulin resistance syndrome (history of the issue, pathogenesis, approaches to treatment) // Collection of scientific papers. – 2000. – 353–363 p.
2. Vikhlyaeva E. M. Guide to endocrine gynecology // Edited by E. M. Vikhlyaeva. – M. – 2004. – 768 p.
3. Demidova T. Yu. Obesity and insulin resistance // Difficult patient. – M. – 2006. – No. 7.
4. Smetnik V.P., Tumilovich L.G. Non-operative gynecology: a guide for doctors. – M.: Med. information Agency. – 2005. – 592 p.
5. Terentyuk V.G. Choice of contraception method in women with normal, overweight and obesity // Medical aspects of women's health. – 2012. – No. 1 (52). – 2–6 s.
6. Manukhin I. B., Gevorkyan M. A., Chagai N. B. Anovulation and insulin resistance. – M. – 2006. – 415 p.
7. Nazarenko T. A. Polycystic ovary syndrome. Modern approaches to the diagnosis and treatment of infertility. – MED press inform. – 2005. – 207 p.
8. Sapozhak I. N. Dissertation for the academic degree of Candidate of Medical Sciences: Pregravid preparation and pregnancy outcomes in women with PCOS against the background of insulin resistance // D. - 2011–12. – 41 s.
9. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) // Hum. Reprod. – 2004. – 19. – P. 41–47

First published: KOSMETIK international journal, No. 1 (55) / 2015, pp. 66-69