Hyperandrogenism: Definition, Causes, Signs, Symptoms, Diagnosis and Treatment

Androgen excess is a common endocrine disorder in women of reproductive age, with a prevalence of 5 to 10%.

Most patients with hyperandrogenism have polycystic ovarian syndrome .

Hyperandrogenism is a term used to describe an excess in the circulating male sex hormone (testosterone) in women; these androgens are produced mainly from the adrenal glands and the ovaries.

However, peripheral tissues such as fat and skin also play a role in the conversion of weak androgens into more potent ones.

Causes

The high levels of circulating male sex hormones observed in female patients can arise from:

Ovarian disease

  • Polycystic ovary syndrome.
  • Benign (non-invasive) or malignant (cancerous) ovarian tumors.

Disease of the adrenal gland

  • Partial deficiency of the 21-hydroxylase enzyme (late-onset CYP21A2 deficiency) and other forms of congenital adrenal hyperplasia.
  • Benign or malignant adrenal tumors.

Disease of the pituitary gland

  • Cushing’s syndrome due to excessive adrenocorticotropic hormone.
  • Acromegaly (gigantism) due to excessive growth hormone and insulin-like growth factor.
  • Prolactinoma, a tumor that produces prolactin, since prolactin stimulates the adrenal gland.

Obesity and metabolic syndrome

The greatest amount of androgens are produced in the adrenal glands and body fat in response to the release of insulin and insulin-like growth factor 1, and less vitamin D is produced in the skin.

Medicines

Some can cause acne , including testosterone, anabolic steroids and recombinant human type 1 insulin growth factor.

The mechanisms that result in hyperandrogenism may involve:

  • High general levels of circulating testosterone.
  • Normal total testosterone but free testosterone increase, due to low levels of sex hormone binding globulin, the protein that carries testosterone in the blood.
  • More active conversion of weaker androgens to stronger androgens such as dihydroxytestosterone by the enzyme type 5-alpha reductase within the sebaceous gland.
  • Adrenal steroids, first converted to androstenedione by 3-beta hydroxysteroid dehydrogenase and then to testosterone by 17-beta hydroxysteroid dehydrogenase.
  • Increased sensitivity of the skin to dihydrotestosterone .
  • Effects of insulin and type 1 insulin growth factor.

Signs and symptoms of hyperandrogenism

The excess of androgens can affect different tissues and organs, causing variable clinical characteristics such as acne, hirsutism, virilization and reproductive dysfunction.

Hyperandrogenism can lead to any of the following:

  • Seborrhea (oily skin)
  • The acne.
  • Hidradenitis suppurativa.
  • The hirsutism.
  • Female pattern baldness (alopecia).
  • Male pattern baldness in women.
  • Irregular menstruation.
  • The masculine appearance with increase of the muscular mass and
    decrease of the size of the breasts.
  • The deepening of the voice with prominent larynx.
  • The enlarged clitoris associated with increased libido (virilization).
  • Sterility
  • Type 2 diabetes associated with insulin resistance.
  • Obesity .

Hyperandrogenism should be considered in any girl who presents hirsutism or equivalents of cutaneous hirsutism, menstrual disorders or central obesity during puberty.

Diagnosis

If there are symptoms or signs suggestive of hyperandrogenism, the initial laboratory investigations may be useful in identifying the exact cause.

Usually the doctor recommends the following tests for diagnosis:

Blood tests for hormones

  • The follicle stimulating hormone.
  • The hormone luteinizing .
  • The estradiol.
  • For prolactin.
  • The testosterone
  • The sex hormone binding globulin.
  • The hormone 17-hydroxyprogesterone.
  • The steroid hormone dehydroepiandrosterone sulfate.
  • The function of the thyroid.

Pelvic ultrasound to evaluate ovarian cysts

The oral contraceptive should be discontinued 6 weeks before the test.

The ideal time is in the first 3 days of the menstrual period and the sample is best taken when fasting.

Elevated testosterone suggests that an ovarian source may be responsible for the signs of hyperandrogenism.

If testosterone levels are only slightly elevated, polycystic ovary syndrome should be considered. If they are markedly elevated, an ovarian tumor should be considered.

The high steroid hormone dehydroepiandrosterone sulfate suggests an adrenal source and an elevated level of 17-hydroxyprogesterone suggests congenital adrenal hyperplasia.

Treatment

Antiandrogen therapy refers to the medication that women take to counteract the effect of male sex hormones, such as testosterone on the skin.

Antiandrogenic medications are used to treat signs of hyperandrogenism, including the following skin and hair disorders:

  • The acne.
  • Seborrhea.
  • The hirsutism.
  • Female pattern hair loss.
  • Hidradenitis suppurativa.

Antiandrogenic therapy can usually cause one of the following effects:

  • Block androgen receptors.
  • Reduce the production of adrenal androgens.
  • Reduce the production of ovarian androgens.
  • Reduce the production of prolactin in the pituitary gland .
  • Inhibit 5-alpha reductase (this enzyme acts on the skin to increase dihydroxytestosterone).
  • Reduce insulin resistance .

The blockers of the androgen receptors act on the sebaceous gland and the base of the hair follicle. These mainly include:

  • The oral contraceptive (contraceptive pill) containing ethinylestrodiol (estrogen) and an antiandrogenic progesterone. These include cyproterone acetate (co-cyprindiol or Diane 35, Estelle 35 and Ginet-84), drospirenone (Yasmin, Yaz) or dienogest (Valette).
  • Other oral contraceptives that combine at low doses with a minimal androgen effect. These contain ethinylestrodiol and desorgestrel, gestodene or norgestimate.
  • Spironolactone 25 to 200 mg per day (Aldactone, Spirotone, Spiractin), which is more useful in women over 30 years.
  • Cyproterone acetate 50 to 200 mg (Androcur, Procur, Siterone). This powerful antiandrogen is usually taken on days 1 to 10 of the menstrual cycle (conventionally, day 1 is the first day of menstruation).
  • Flutamide 250 to 500 mg per day. This is usually used as a hormonal antineoplastic agent in men with prostate cancer. It can also cause hepatitis and it should not be used for skin disorders.

Spironolactone and cyproterone can be effectively combined with cyproterone acetate and ethinyloestradiol or another oral contraceptive agent, partly because they cause menstrual irregularities and partly to prevent pregnancy.

Combination therapy is not necessary in post-menopausal women.

Low doses of oral corticosteroids ( Prednisone 2.5 mg in the morning, 5 mg in the evening) act to reduce adrenal androgen production. In congenital adrenal hyperplasia, the levels of the hormone dehydroepiandrosterone sulfate should be reduced to normal.

Limecycline, roxithromycin and ketoconazole are antimicrobial drugs that have also been observed to reduce androgen synthesis.

Medications that act on the production of ovarian androgens include:

  • Gonadotrophin receptor hormone (buserelin, leuprolide) agonist, which stops ovulation and suppresses androgen production. Because they also stop the production of estrogen, they can cause symptoms of menopause, headache and osteoporosis.
  • Combined oral contraceptives.
  • Progestinas.

Excess prolactin is reduced with bromocriptine, cabergoline and quinagolide.

Inhibitors of 5-alpha reductase include zinc, finasteride, azelaic acid, wild palm heart and other plant extracts.

Spironolactone inhibits 5-alpha reductase weakly.

Unfortunately, finasteride does not reduce sebum production and is not effective in the treatment of acne.

However, we now know that isotretinoin reduces sebum in part by reducing the production of dihyrotestosterone in the sebaceous glands.

Insulin resistance can be reduced by using metformin, mainly prescribed for type 2 diabetes mellitus and obesity and metabolic syndrome. It can also reduce the signs of hyperandrogenism.

Metformin 250 mg to 2 g daily is safe but can cause diarrhea and should be taken after food in gradually increasing doses.

Rosiglitazone and pioglitazone can cause toxicity to the heart and liver.

In acne, the effects of anti-androgens include:

  • The reduction of sebum production.
  • The reduction of the formation of comedones.

They can be combined with other topical and oral treatments for acne.

In hirsutism, the results are:

  • The much slower hair growth.
  • The color of the hair lighter.
  • The hair with the finest texture.

Physical methods of hair removal such as hair removal, shaving, electrolysis or hair removal laser can be used at the same time as anti-androgens are taken. They often work better than before medication.

In female pattern hair loss, the results are:

  • The reduction of hair loss.
  • Thinning of the hair is reduced.
  • Sometimes, the thicker hair restoration occurs.

These effects are not always clinically significant.