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dehydroepiandrosterone; prasterone (DHEA, Aslera, Intrarosa)

In females: 1) derived largely from the adrenals (80%) 2) 20% derived from ovaries - theca cell systems is the source of ovarian androgens 30-50 mg/day is produced by zona fasciculata & zona reticularis of the adrenal cortex. Quantitatively, the major secretory product of the adrenal gland. Adrenal production is regulated by ACTH. No known receptors for DHEA. Activity appears to be solely due to activity of its 2 metabolites, testosterone & estrone. Concentrated in specific areas of the paleocortex in humans. Pharmacology: prasterone. Tradenames: Aslera, Intrarosa. Indications: 1) treatment of lupus erythematosus (possibly) 2) androgen replacement in women with adrenal insufficiency [5] 3) metabolic syndrome X ? [6,7] 4) dyspareunia in postmenopausal women (FDA-approved Nov 2016) [13] - genitourinary syndrome of menopause 5) NO solid evidence to support popular uses: a) anti-aging factor - 50 mg/day of no benefit to healthy older women [9] b) appetite suppressant c) immune enhancer d) modulator of affect e) prevention of cardiovascular disease [8] f) no significant benefits on - body composition, physical performance, insulin sensitivity, quality of life [10] Dosage: 50-200 mg PO QD Tabs: 200 mg (Aslera) Once a day vaginal insert for dyspareunia (Intrarosa) Pharmacokinetics: 1) inhibits cyt P450 3A4 2) metabolized to testosterone & estradiol [6] Monitor: liver function tests [4] Adverse effects: 1) concern derived from observation that DHEA is a precursor of testosterone & estradiol [6] 2) women: weight gain, voice changes, facial hair, headaches 2) males: gynecomastia, BPH, 3) can lower HDL cholesterol Drug interactions: - may increase serum levels of a) triazolam b) ketoconazole c) felodipine (other calcium channel blockers [12]?) d) simvastatin e) others - sildenafil Mechanism of action: 1) increases DHEA-sulfate levels 2) may improve libido in women 3) weak androgen 4) activates PPAR-alpha (regulation of adipocyte physiology) 5) may reduce abdominal fat (including visceral) in elderly [6,7] 6) increases bone mineral density in elderly women with low pretreatment levels of DHEA [8]

Interactions

molecular events drug adverse effects of androgens

Related

steroid biosynthesis

Specific

dehydroepiandrosterone sulfate (DHEA-SO4)

General

17 ketosteroid androgen or anabolic steroid androstenol

Database Correlations

PUBCHEM correlations

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 243
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  3. Prescriber's Letter 7(12):70 2000
  4. Prescriber's Letter 8(8):48 2001
  5. Solomon D. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  6. Prescriber's Letter 12(1): 2005 DHEA and Abdominal Obesity Detail-Document#: 210115 (subscription needed) http://www.prescribersletter.com
  7. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004 Nov 10;292(18):2243-8. PMID: 15536111
  8. Olech E & Merril JT, DHEA supplementation: The claims in perspective, Cleveland Clinic Journal of Medicine 72(11): 965, 2005
  9. Nair KS et al DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006 Oct 19; 355:1647-59 PMID: 17050889 - Stewart PM. Aging and fountain-of-youth hormones. N Engl J Med 2006 Oct 19; 355:1724-6 PMID: 17050897
  10. Prescriber's Letter 13(12): 2006 Anti-aging effects of DHEA Detail-Document#: 221208 (subscription needed) http://www.prescribersletter.com
  11. Igwebuike A et al, Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal women. J Clin Endocrinol 2008, 93:534 PMID: 18029465
  12. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  13. Brooks M FDA OKs Prasterone for Dyspareunia in Postmenopausal Women. Medscape. Nov 17, 2016 http://www.medscape.com/viewarticle/872022 - FDA News Release. November 17, 2016 FDA approves Intrarosa for postmenopausal women experiencing pain during sex. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm529641.htm

Substructure-of

7-keto dehydroepiandrosterone