Causes of Androgen Insufficiency

Bilateral oophorectomy, hypopituitarism, adrenal insufficiency and premature ovarian failure result in about 50% reduction in androgen production.

Sex hormone binding globulin (SHBG) is a pivotal determinant of the bioavailability of sex steroids and variations in the plasma levels of SHBG impact significantly on the amount of free, or bioavailable testosterone and other bound sex steroids.

In normal reproductive aged women 82% of the binding sites of SHBG are unoccupied. For the occupied binding sites, androstenediol (5.1%) is the major SHBG ligand followed by DHEA (3.6%), testosterone (2.3%), cortisol (2%) cortisone (1.9%), DHT (1.4%) and androstenedione (1.0%). Conversely, the binding affinity for steroids bound by SHBG is DHT> testosterone > androstenediol > estradiol > estrone. SHBG also weakly binds DHEA, but not DHEA-S.

Under normal physiological conditions in women only 1 to 2 % of total circulating testosterone is free or biologically available. The rest is bound by SHBG (66%) and albumin (30%). Elevations in estradiol (as occurs during pregnancy), hyperthyroidism and liver disease cause a marked increase in SHBG levels, whereas hypothyroidism, obesity, and hyperinsulinemia are associated with decreased SHBG levels.

In addition oral administration of steroid hormones and their analogues can markedly alter SHBG levels whereas parenteral administration of these compounds typically has a much weaker influence. Standard dose of oral estrogen as used in hormone therapy (HT) will increase SHBG with little or no effect seen with standard estradiol patch therapy. The consequence of the oral administration of estrogens is an increase in SHBG which binds available testosterone and reduces free testosterone levels. This reduction of bioavailable testosterone potentiates the likelihood females exhibiting signs and symptoms of androgen deficiency.

Factors which can increase SHBG include:

  • Oral estrogens (including oral contraceptives, HRT tablets)
  • Thyroxine
  • Increasing age
  • Alcohol
  • Smoking
  • Some anticonvulsants e.g. phenytoin
  • Pregnancy
  • Reduced liver function

Not directly linked to androgen production, but an important consideration in determining causes of decreased sexual desire is the use of medications.

Medications which may interfere with sexual desire include:

Medication Use
SSRI's, tricyclics Depression
Oral oestrogens Oral contraceptive pill, HRT
Medroxyprogesterone Contraceptive,HRT
Clonidine Hot flushes
Spironolactone,Androcur Hirsutism
Danazol Endometriosis
Benzodiazepines Anxiety,insomnia
Β blockers Hypertension
H2 antagonists Oesophageal reflux
Ketoconazole Vuvlo-vaginal candidiasis
Gemfibrazol Hyperlipidaemia