Adrenopause: Drug Therapy

Therapeutic target

Improvement of symptoms and complaints indicative of adrenopause.

Therapy recommendations

  • DHEA hormone replacement therapy

Indications (areas of application) for DHEA hormone replacement therapy

The indications for DHEA hormone replacement therapy are:

  • Primary and secondary adrenal insufficiency.
  • Androgen deficiency in postmenopausal women, e.g., after removal of the ovaries or under glucocorticoid therapy (cortisol)
  • DHEA levels below the age-specific normal limit – the goal is to raise serum DHEA levels back to the level at age 25-30 years:
    • Male: 280-640 µg/dl (2,800-6,400) ng/ml – minimum 350 µg/dl (3,500 ng/ml).
    • Woman: 100-300 µg/dl (1,000-3,000 ng/ml) – at least 200 µg/dl (-250 µg/dl) (2,500 ng/ml).
  • Assured DHEA-specific indications – with concomitant assured DHEA-S levels below the age-appropriate sex-specific serum DHEA-S levels for men and for women, respectively.

Contraindications

DHEA (prasterone (INN)) should not be administered in diagnosed hormone-related carcinomas – mammary (breast), ovarian (ovary) and endometrial (endometrium), prostate – because there is no confirmed experience on the effect of DHEA on these tumors. Because DHEA is a precursor of estrogens (17-beta-estradiol, estrone) and androgens (androstenedione, testosterone), it is theoretically possible that the growth of hormone-dependent carcinomas is promoted by taking DHEA. In the case of an overdose of DHEA in women, testosterone-related acne (e.g. acne vulgaris), alopecia (hair loss) and, in rare cases, hirsutism – increased hair growth of the male type, e.g. beard growth – may occur. DHEA substitution should be avoided during pregnancy and breastfeeding. Since orally taken DHEA is metabolized in the liver and released from there into the bloodstream, patients with liver disease and DHEA hormone replacement therapy should always have close monitoring of the liver enzymes alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT) and gamma-glutamyl transferase (γ-GT, gamma-GT; GGT). Estrogen-related edema and weight gain may occur with DHEA overdose in men.

Mode of action

DHEA is metabolized to androstenedione and testosterone in women, and to 17-beta-estradiol and estrone in men.The normal 17-beta-estradiol serum level in men is 12-34 pg/ml (44.1-124.8 pmol/l). This level should not be exceeded during DHEA substitution therapy.Furthermore, DHEA has a neurosteroidal effect: it interacts with various intracerebral receptors such as NMDA and GABAA receptors. The importance of DHEA for neuronal metabolism is demonstrated by the proven DHEA synthesis in the brain.The positive effects of DHEA for women were first known – in the meantime, confirmed positive effects have been demonstrated for women and men:

  • Improved well-being and increase libido in women, supportive therapy of erectile dysfunction in men.
  • In postmenopausal women, DHEA treatment (5-25 mg/day) may be indicated if the symptom of postmenopausal androgen deficiency – for example, libido disturbance – can be confirmed. The conversion of DHEA to testosterone and androstenedione in women leads to an effective substitution of the missing testosterone.Furthermore, DHEA has a positive influence on the vaginal epithelium (vaginal cytology). This is normalized back to conditions of fertile women and thus “rejuvenated”. At the same time, the endometrium remains atrophic, which means a favorable selective estrogen effect of DHEA in terms of SERM (Selective Estrogen Receptor Modulator).
  • Osteotropic effects – improved bone density in women and in men.
  • Metabolic syndrome – improved insulin sensitivity with decrease in HbA1c in men.
  • Prevention of oxidative stress and formation of “advanced glycation endproducts” (AGE; AGEs) in type 2 diabetes mellitus. AGEs are advanced glycation endproducts; these are the result of non-enzymatic glycation (also glycation) in the Maillard reaction of carbohydrates (eg.(e.g. glucose) and an amino-terminal group of a protein, lipid or nucleic acid (the best known representative is deoxyribonucleic acid (DNA)).The intake of 50 mg DHEA resulted in decreased oxidative stress (measured were decreased levels of reactive oxidative species (ROS), increased levels of glutathione and vitamin E; serum pentosidine levels were decreased by half, indicating a reduction of AGEs. These results present in the aggregate, compared to the placebo group). This indicates that the cellular damage induced by hyperglycemia may be reduced by DHEAS therapy.
  • Stimulation of STH – Growth hormone stimulation and consequently increased production of IGF-1, which increases NK cell activity (stimulation of the immune system)Note: NK cells are among the mainstays of cellular immune defense – especially in viral infections and tumor diseases.
  • Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis.
  • Depression and depressive symptoms: DHEA showed promising positive results in mild or resistant to conventional therapy.

Dosage information

DHEA is currently not available in Germany as a finished drug, but must be ordered abroad or is individually dosed by a pharmacist in a German pharmacy on an individual prescription. DHEA is available as a tablet for oral administration in dosages usually of 25 mg and 50 mg. However, individually dosed confections are required for fine-tuning. Dosage for women is usually between 5-20 mg daily and for men between 15-75 mg (single morning dose).Blood monitoring (DHEAS) preferably three to five hours after a morning DHEA administration then allows target ranges of 98.8-340 (optimum: 200-280) µg/dl in women and 160-449 (optimum: 400-450) µg/dl in men. In the absence of further evidence and clinical experience on the effects of DHEA in the context of longer-term DHEA treatment, the decision to substitute remains both a matter of discretion in terms of a risk-benefit assessment on the part of the endocrinologically experienced physician and an autonomous decision on the part of the patient concerned.

Supplements (dietary supplements; vital substances)

In the presence of insomnia (sleep disturbances) due to adrenopause, see Insomnia/Medicinal Therapy/Supplements below.