Hirsuitism -Causes and Treatment

 

Hirsutism (Androgen Excess Syndrome)

Hirsutism is defined as presence of excessive amount of coarse hair of male distribution seen in a female, causing unacceptable cosmetic concern. Such areas include face, chest, abdomen, thighs and back, etc. A semi-quantitative analysis of hirsutism can be made according to Ferriman D and Gallwey JD Nine body areas of hormone sensitivity for hair growth are graded from 1 to 4 (minimal hair to frank virilization) and ultimately the grades in each of these areas are summed together. If the score is more that 8 it indicates hirsutism. The amount of hair growth differs among various ethnic and genetic groups. It is much decreased in Orientals, for example the Chinese and increased in Mediterranean’s. Hirsutism must not be confused with virilization. Hirsutism does not always signify major pathology or serious endocrine disturbance. In several hirsute women the disturbance is due to excessive activity of 5 alpha reductase in the skin. The enzyme releases dihydrotestosterone (DHT) from testosterone carried along with sex hormone binding globulin (SHBG). Hirsutism may also occur due to excessive sensitivity of hair follicles to DHT. This kind of sensitivity is known as constitutional Hirsutism of no serious pathological significance except that it is unacceptable to the patient. But hirsutism can also be the earliest sign of a serious disorder like an androgen producing tumor. Hirsutism of recent organ must be viewed with suspicion particularly if the degree of hirsutes is increasing with time. This is due to androgen levels increasing in the system caused probably by neoplasm. Frank virilization characterized by clitoromegaly deepening of voice and alopecia may all follow this kind of hirsutism.

Androgen excess syndrome can occur due to several causes. Sixty to eighty percent of these women are said to be having PCO syndrome. The syndrome is seen in 5 percent of general population of reproductive age group. They may not all be infertile nor will they all be hirsute. Forty to sixty percent of them are obese 50 to 90 percent are oligomenorrheic and 50 to 70 percent of them may have hirsutism of low or high order. The high level of androgens and cyclical estrogen production causes disruption of HT-HP gonadal axis resulting in elevated LH-FSH ratio. Many women with PCO have metabolic disturnances some showing insulin resistance and compensatory hyperinsulinemia with or without abnormal glucose tolerance (GT). Some of the women with PCOS have dyslipidemia caused both by high levels of insulin and androgens. Hirsutism caused by hyperinsulinemia may show at least a partial response to administration of insulin sensitizing agents like metformin.

HAIR –AN Ssyndrome: This syndrome connotes a group of symptoms, which include hyperandrogenism, insulin resistance and acanthosis nigricans  In this syndrome, the predominant feature is hyperinsulinemia due to insulin resistance. The mitogenic action of insulin on the basal cells of epididymis causes a velvety hyperpigmented patches or streaks in skin creases. Although PCOS is also along with HAIR-AN syndrome the degree of metabolic disturbance seen in HAIR-AN syndrome can be of a much higher order.

Congenital Adrenal Hyperplasia(CAH) is a disorder caused by deficiency of 21 hydroxylase enzyme

Cushing syndrome: The clinical presentation of this syndrome is primarily that of abnormal fat deposition of the body, thinning of skin with striae,  glucose intolerance, osteoporosis, muscle weakness along with all the other signs of PCO syndrome.

Androgenic tumors: Androgens producing tumors of ovary or adrenal gland can cause hirsutism. But they are rare. This should be suspected when the onset of symptoms are sudden and the progression is rapid. Hormone producing tumors are usually of low malignancy. When signs of excessive secretions of cortisol are present associated with virilization one must look for adrenal tumors or secondary androgenism caused by PCO syndrome, etc. Unlike PCO or Cushingoid pathology, Virilizing ovarian tumors exhibit the form of sudden onset of hyper-androgenism with frank virilization. These include Sertoli-Leydig cells and lipoid cell tumors.

Hyperthecosis: is a rare condition characterized by diffuse luteization and hyperplasia of ovarian stroma; plasma testosterone is often elevated. This is not a tumor. It can be a variant of PCO.

Scoring system in hirsutism: Several scoring systems are known. The one that is most accepted is that of Ferriman Gallwey.

1. Constitutional hirsutism can only be treated by cosmetologist.

2. Androgen producing neoplasm must be removed surgically.

3. Iatrogenic disorders cab be treated by withdrawing the treatment.

4. Other types of Non-neoplastic hirsutism can be treated medically.

Medical treatment of hirsutism.

• The condition of PCO has to be treated in a different fashion. If the woman is desirous of treatment for infertility, she must be made to understand that it is not possible to treat Hirsutism and fertility enhancement at the same time.

• If patient is worried about amenorrhea, she may be given medroxyprogesterone acetate 10mg/day from the 1st of every month for 12 days. The period will be expected on 14th or 15th of the month. This would not only regularize her periods but it will also stop excessive endometrial hyperplasia.

• If the patient is hyperinsulinemic likewise she may be given metformin for 500 to 1500 mg/day. If insulin is reduced by this therapy SHBG will increase and free testosterone reduced. This may help in reducing hirsutism.

• If the patient is only worried about hirsutism, estrogen progesterone pills may be given in the form of oral contraceptive pills. This would increase SHCG and decrease free testosterone.

USE OF ANTI ANDROGENS(AA): Anti-androgens are available is the form of spironolactone and cyproterone acetate. Spironolactone is an aldosterone antagonist and also a mild diuretic. It competes with circulating androgens for the androgen receptor; it also has a suppressive effect on various enzymes where androgen biosynthesis occurs. Spironolactone can be given along with OC pills so that the patient can continue to have monthly periods. The dose of spironolactone can be built up to 100 to 250 mg/day over a period of 2 to 4 weeks.

CYPROTERONE ACETATE(CAP): CAP is another progesterone derivative and is also an anti-androgen. It is available in the form of 25 mg tablets and also in the form of a combination pill with ethinylestradiol. The 25 mg tablets of cyproterone is a very powerful drug and can be given at a dose of 1 pill/day. CPA decreases circulating LH levels and thus reduces androgens at peripheral levels. CPA can be used along with spironolactone. One hirsutism is reduced to an acceptable levels, one can change over to combination pill of Cyproterone with ethinylestradiol. These are contraceptive pills particularly manufactured for hyperandrogenized women.

5 alpha-reductase inhibitors: Finasteride is a 5 alpha reductase inhibitors working at the skin level, so that the DHT level is reduced. Since it is teratogen ic, it can obly be used in women who are not trying for pregnancy.

Long acting GnRH analogues. The depot GnRH agonists may be given at monthly intervals to suppress HT-HP ovarian axis. These can be given over several months. But it cause intense degree of hypoestrogenemia and thios would require the need for estrogen addback therapy to prevent osteoporosis, calcium depletion, dyspareunia,ect. Use of GnRH agonist is an expensive therapy. In women over 40 who are suffering from extreme grade of hirsutism, GnRH agonist therapy may be given as a therapeutic test. GnRH agonist may be given in the form of a depot injection at monthly intervals over a period of 4 to 5 months. If this shows a substantial improvement, the patient may be counselled to have a bilateral oophorectomy after which they can proceed to take estrogen progesterone therapy for a few years or until the age of natural menopause.

CORTICOSTEROID THERAPY: Prednisone 5 to 10 mg or hydrocortisone 15 mg or dexamethasone 0.5 mg may be given in daily doses. This may be used in women with borderline, occult or overt adrenal hyperplasis. This would reduce the level of ACTH secretion from the pituitary gland, which in turn will reduce the release of 17 hydroxy progesterone.

KETOCONOZOLE: Ketoconazole is an antifungal agent, which inhibits adrenal and ovarian androgen-biosynthesis. The drug can suppress adrenal corted to an extent that it can even produce adrenal crisis. In view of this, this drug is not freely used.

MECHANICAL DEPILATION: Along with hormone therapy, the patient must help herself by added procedures like plucking, Bleaching can be useful. Shaving does not lead to worsening of hirsutism. On the other hand it may be a safer method of removing the hair than plucking or wacing. Terminal hairs, which have been persisting for a long time, may not disappear. This can be removed by electrolysis.

Hormonal suppression should be continued as long as the ovaries are present. The patients with established hirsutism may have to wait for 12 to 18 moths before the situation comes under reasonable control. Even menopausal ovaries are said to produce significant amounts of androgens. In view of this such women can be counselled for oophorectomy