Hyperandrogenism

What is hyperandrogenism?

Hyperandrogenism describes excessive circulating male sex hormone (testosterone) in females and its effects on the body.

What causes hyperandrogenism?

High levels of circulating male sex hormones in females may arise from:

• Disease of the ovaries
  • Polycystic ovary syndrome
  • Benign (non-invasive) or malignant (cancerous) ovarian tumours
• Disease of the adrenal gland
  • Partial deficiency of the adrenal enzyme 21-hydroxylase (late onset CYP21A2 deficiency) and other forms of congenital adrenal hyperplasia
  • Benign or malignant adrenal tumours
• Disease of the pituitary gland
  • Cushing syndrome due to excessive adrenocorticotrophic hormone (ACTH)
  • Acromegaly (gigantism) due to excessive growth hormone and insulin-like growth factor (IFG-1)
  • Prolactinoma, a tumour that produces prolactin, as prolactin stimulates the adrenal gland
• Obesity and the metabolic syndrome – more androgens are made by the adrenals and in body fat in response to release of insulin and IFG-1, and less vitamin-D is produced in the skin
• Medications that may cause acne, including testosterone, anabolic steroids and recombinant human IGF-1

The mechanisms that result in hyperandrogenism may involve:

• High overall levels of circulating testosterone
• Normal overall testosterone but increased free testosterone, due to low levels of circulating sex-hormone-binding-globulin (SHBG, the protein that carries testosterone in the blood). Normally there is little free testosterone circulating in the blood as testosterone is tightly bound by SHBG
• More active conversion of weaker androgens to stronger androgens such as dihydroxytestosterone (DHT) by the enzyme Type 1 5-alpha-reductase within the sebaceous gland
• Adrenal steroids converted first to androstenedione by 3-beta-hydroxysteroid dehydrogenase then to testosterone by 17-beta hydroxysteroid dehydrogenase.
• The higher sensitivity of the skin to DHT
• Effects of insulin and IGF-1

What are the effects of hyperandrogenism?

Hyperandrogenism can lead to any or all of the following:

• Seborrhoea (oily skin)
• Acne
• Hidradenitis suppurativa
• Hirsutism
• Female pattern balding (alopecia)
• Male pattern balding in females
• Irregular menstruation
• Masculine appearance with increased muscle mass and decreased breast size
• Deepening of voice with prominent larynx (voice box)
• Clitoral enlargement associated with increased libido (virilisation)
• Infertility
• Associated type 2 diabetes due to insulin resistance
• Obesity

Acne 

Hirsutism 

Pattern alopecia 

What tests are necessary to confirm hyperandrogenism?

If there are symptoms or signs to suggest hyperandrogenism, baseline laboratory investigations may be useful to identify the exact cause.

• Blood tests for hormones:
  • FSH (follicle stimulating hormone)
  • LH (luteinising hormone)
  • Oestradiol
  • Prolactin
  • Testosterone
  • SHBG (sex hormone binding globulin)
  • 17-hydroxyprogesterone
  • DHEAS
  • Thyroid function.
• Pelvic ultrasound scan to evaluate ovarian cysts

The oral contraceptive should be stopped 6 weeks before testing. The ideal time is in the first 3 days of the menstrual period and the sample is best taken when fasting.

Elevated testosterone suggests an ovarian source may be responsible for the signs of hyperandrogenism. If the levels of testosterone are only mildly elevated, consider polycystic ovary syndrome, if they are markedly elevated, consider an ovarian tumour.

Elevated DHEAS suggests an adrenal source and an elevated 17-hydroxyprogesterone level suggests congenital adrenal hyperplasia.

My test results are normal. Why do I have acne/hirsutism?

Most females with acne/hirsutism have similar levels of hormones to unaffected women. This indicates their acne/hirsutism is not due to disease of the ovary, adrenal gland or pituitary gland.

Some women have more activity of the enzyme 5-reductase within their sebaceous glands. This leads to more male hormone dihydrotestosterone within the cell, which can explain acne and hirsutism. Other causes of acne include hereditary and environmental factors.

Should I consult a hormone specialist?

Most women with acne and/or hirsutism can be managed by a family doctor/GP or by a dermatologist.

Patients with acne and significant menstrual disturbance, severe hirsutism, suspected Cushing syndrome or acromegaly, total testosterone of > 5 nmol/L or other hormone abnormalities are best to consult an endocrinologist (hormone specialist).

Hormone therapy

Treatment for patients with acne includes topical antiacne agents, oral antibiotics such as tetracycline, antiandrogens (hormone therapy, including birth control pill) and oral isotretinoin. These can be used successfully in patients with and without hyperandrogenism.

Most women with hirsutism use physical methods of hair removal and may take the birth control pill.

However, when acne and/or hirsutism are unresponsive to conventional therapy because of hormone imbalances, more potent antiandrogens may be considered.