O-81:Management Of Hirsutism



Androgens constitute an important physiologic component for the female, representing the principal precursors of estrogens and directly participating to the secondary sexual characters determinism and to the sexual identity and behaviour definition. Androgens play several and important metabolic effects, acting, moreover, in the regulation of a number of the female organism functions. A regular and adequate ovarian and adrenal production of that hormonal fraction is essential for the activation and the modulation of important physiologic functions as: 1) Maintaining and regulation of the normal steroidogenic processes, acting as fundamental precursors for the global production of sexual steroids; 2) Induction of the process of follicular atresia following the selection of the dominant follicle; 3) Trophism of some tissues (especially of skin, bone and muscles); 4) Modulation of libido and sexual procectivity, in synergism with psycho-emotive and socialbehavioural factors. However, a condition of hyperandrogenism, due to excess of the steroid production or to increase of its biological activity, may determinate serious negative consequences which, often, impair not only the aesthetic aspect but also the psychic area and the interpersonal relationships. Not less important are the repercussions on the metabolic asset and, in successive phases of the life, on the cardiovascular risk. That situation appears more and more important considering that up to 10% of adolescent women complain with a symptomatology related to an excessive androgen activity, even if the correct prevalence of the phenomenon could be largely affected by the diagnostic criteria utilized. With the term of “hyperandrogenism” are identified all these clinical-pathologic conditions characterized by the presence of over-physiologic levels of androgenic steroids and/or the increased receptor sensitivity at the level of target tissues with consequent exaltation of the final biological effect . On the other hand, with “hyperandrogenic state” are identified all these clinicalpathologic conditions, with multifactorial aetiology characterized by: 1) Increased body hair growth in normally smooth skin areas and/or with only little hair follicles (face, thorax, abdomen, gluteus, alba line) and increased growth speed of the hair structures; 2) Increased sebaceous production of the skin (in areas normally rich in sebaceous glands) and at the level of the scalp; 3) Alopecia; 4) Variable degrees of insulin resistance and/or hyperinsulinemia; 5) Reduction of the circulating levels of HDL cholesterol and modification of its rate with total cholesterol; 6) Alteration of the normal processes of ovarian follicle genesis with increasing of follicular atresia and failure on the selection and dominance of pre-ovular follicle; increase of ovarian stroma, albuginea thickening and formation of follicular micro-cysts. Excluding neoplastic and hyatrogenic aetiology the so called functional causes of Abstract of the 8th Royan International Twin Congress, Tehran, Iran, 5-7 September 2007 48 Yakhteh Medical Journal, Vol 9, Sup 1, Summer 2007 hyperandrogenism are usually characterized by a multifactorial aetiopathogenesis. Policystic ovarian syndrome (PCOS) represents the most frequent cause of hyperandrogenism in post-pubertal age. This complex disendocriny, which presents chronicity and self-maintaing aspects, is characterized by a severe disarray of the principal intra- and extra-ovarian feed-back mechanisms, presenting with a wide clinical, morphological and endocrine-metabolic variability. Among all the causes of hyperandrogenism, PCOS is the most important under the etiophatogenic and prognostic aspect, often associating with characteristic dismetabolisms as dislipidemia (low levels of HDL cholesterol, alteration of total cholesterol/HDL cholesterol rate), impaired carbohydrates tolerance, insulin-resistance, overweight and obesity. According to that condition several therapeutic options have been proposed over the years. General measures are represented by eliminate causative factors, optimizing weight and manage hair with bleaching, cutting or shaving, electrolysis, laser epilation, but nowadays the most utilized and efficacious are represented by the etiphatogenetic therapy: 1) Ovarian andorgens production inhibitors (oral contraceptives, GnRH analogues); 2) Androgens receptor antagonists (ciproterone acetate, flutamide); 3) 5-alpha-reductase inhibitors (finasteride, dutasteride); 4) Insulin sensitizers (metformin, acarbose). Oral contraceptives can be administered alone or in association with antiandrogens, insulin sensitizers or GnRH analogues. Ciproterone acetate has been largely utilized with great success. It can be administered in low dosage being effective on acne/seborrhoea more than in hirsutism. The inverted sequential regimen according to Hammerstein, in association with low dose of estrogens, seems to be effective with Ferriman & Gallway hirsutism scores higher than 15, in presence of androgenic alopecia or impaired tolerance to estradiol (>20mcg). Low dosage of ciproterone acetate in association with GnRH analogues are often utilized in the treatment of poor responsive women in assisted reproduction protocols. Finally, low dosage in association with estrogens show same effectiveness vs GnRHA characterizing as secondary choice in severe cases, for the absence of pituitary suppression. Long term administration of ciproterone acetate plus contraceptive pill may, however, determine side effects as headache, nausea, depression, weight increase, hepatic function impairment and increase in triglycerides blood level. More innovative appears the approach with insulin sensitizers. Several research demonstrated the key pathogenetic role played by hyperinsulinemia in the ovarian androgen overproduction of PCOS. On that purpose the reduction of hyperinsulinemia ameliorate the androgen excess.