Androgen deficiency
Androgen deficiency is a medical condition characterized by insufficient androgenic activity in the body. Androgen deficiency most commonly affects women, and is also called Female androgen insufficiency syndrome (FAIS), although it can happen in both sexes.[2][3] Androgenic activity is mediated by androgens (a class of steroid hormones with varying affinities for the androgen receptor), and is dependent on various factors including androgen receptor abundance, sensitivity and function. Androgen deficiency is associated with lack of energy and motivation, depression, lack of desire (libido), and in more severe cases changes in secondary sex characteristics.[3][4][5][6][7][8]
Androgen deficiency | |
---|---|
Other names | Hypoandrogenism, androgen deficiency syndrome, men with hypogonadism,[1] testosterone deficiency |
Signs and symptoms
Symptoms of the condition in males consist of loss of libido, impotence, infertility, shrinkage of the testicles, penis, and prostate, diminished masculinization (e.g., decreased facial and body hair growth), low muscle mass, anxiety, depression, fatigue, vasomotor symptoms (hot flashes), insomnia, headaches, cardiomyopathy and osteoporosis. In addition, symptoms of hyperestrogenism, such as gynecomastia and feminization, may be concurrently present in males.
In males, a type of myopathy can result from androgen deficiency known as testosterone deficiency myopathy or (hypogonadotropic) hypogonadism with myopathy. Signs and symptoms include elevated serum CK, symmetrical muscle wasting and muscle weakness (predominantly proximal), a burning sensation in the feet at night, waddling gait, and impaired fasting glucose. EMG showed low volitional contraction of short duration polyphasic units. Muscle biopsy showed evidence of myonecrosis and regeneration, some fibre splitting, chronic inflammatory cells (macrophages) infiltrating degenerating fibres, and an increase in adipose and fibrous tissue (fibrosis). A predominance of type I (slow-twitch/oxidative) muscle fibres, with some mixed atrophy of type II (fast-twitch/glycolytic) muscle fibres. Treatment is hormone replacement therapy of testosterone.[9][10][11]
In females, hypoandrogenism consist of loss of libido, decreased body hair growth, depression, fatigue, vaginal vasocongestion (which can result in cramps), vasomotor symptoms (e.g., hot flashes and palpitations), insomnia, headaches, osteoporosis and reduced muscle mass.[12][13][14] As estrogens are synthesized from androgens, symptoms of hypoestrogenism may be present in both sexes in cases of severe androgen deficiency.
Causes
Hypoandrogenism is primarily caused by either dysfunction, failure, or absence of the gonads (hypergonadotropic) or impairment of the hypothalamus or pituitary gland (hypogonadotropic). This in turn can be caused by a multitude of different stimuli, including genetic conditions (e.g., GnRH/gonadotropin insensitivity and enzymatic defects of steroidogenesis), tumors, trauma, surgery, autoimmunity, radiation, infections, toxins, drugs, and many others. It may also be the result of conditions such as androgen insensitivity syndrome or hyperestrogenism. Old age may also be a factor in the development of hypoandrogenism, as androgen levels decline with age.
Diagnosis
Diagnosis of androgenic deficiency in males is based on symptoms together with at least two measurements of testosterone done first thing in the morning after a period of not eating.[1] In those without symptoms, testing is not generally recommended.[1] Androgen deficiency is not usually checked for diagnosis in healthy women.[15]
Treatment
Treatment may consist of hormone replacement therapy with androgens in those with symptoms.[1] Treatment mostly improves sexual function in males.[1]
Gonadotropin-releasing hormone (GnRH)/GnRH agonists or gonadotropins may be given (in the case of hypogonadotropic hypoandrogenism). The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging.[16] The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.[16]
Route | Medication | Major brand names | Form | Dosage |
---|---|---|---|---|
Oral | Testosteronea | – | Tablet | 400–800 mg/day (in divided doses) |
Testosterone undecanoate | Andriol, Jatenzo | Capsule | 40–80 mg/2–4x day (with meals) | |
Methyltestosteroneb | Android, Metandren, Testred | Tablet | 10–50 mg/day | |
Fluoxymesteroneb | Halotestin, Ora-Testryl, Ultandren | Tablet | 5–20 mg/day | |
Metandienoneb | Dianabol | Tablet | 5–15 mg/day | |
Mesteroloneb | Proviron | Tablet | 25–150 mg/day | |
Sublingual | Testosteroneb | Testoral | Tablet | 5–10 mg 1–4x/day |
Methyltestosteroneb | Metandren, Oreton Methyl | Tablet | 10–30 mg/day | |
Buccal | Testosterone | Striant | Tablet | 30 mg 2x/day |
Methyltestosteroneb | Metandren, Oreton Methyl | Tablet | 5–25 mg/day | |
Transdermal | Testosterone | AndroGel, Testim, TestoGel | Gel | 25–125 mg/day |
Androderm, AndroPatch, TestoPatch | Non-scrotal patch | 2.5–15 mg/day | ||
Testoderm | Scrotal patch | 4–6 mg/day | ||
Axiron | Axillary solution | 30–120 mg/day | ||
Androstanolone (DHT) | Andractim | Gel | 100–250 mg/day | |
Rectal | Testosterone | Rektandron, Testosteronb | Suppository | 40 mg 2–3x/day |
Injection (IMTooltip intramuscular injection or SCTooltip subcutaneous injection) | Testosterone | Andronaq, Sterotate, Virosterone | Aqueous suspension | 10–50 mg 2–3x/week |
Testosterone propionateb | Testoviron | Oil solution | 10–50 mg 2–3x/week | |
Testosterone enanthate | Delatestryl | Oil solution | 50–250 mg 1x/1–4 weeks | |
Xyosted | Auto-injector | 50–100 mg 1x/week | ||
Testosterone cypionate | Depo-Testosterone | Oil solution | 50–250 mg 1x/1–4 weeks | |
Testosterone isobutyrate | Agovirin Depot | Aqueous suspension | 50–100 mg 1x/1–2 weeks | |
Testosterone phenylacetateb | Perandren, Androject | Oil solution | 50–200 mg 1x/3–5 weeks | |
Mixed testosterone esters | Sustanon 100, Sustanon 250 | Oil solution | 50–250 mg 1x/2–4 weeks | |
Testosterone undecanoate | Aveed, Nebido | Oil solution | 750–1,000 mg 1x/10–14 weeks | |
Testosterone buciclatea | – | Aqueous suspension | 600–1,000 mg 1x/12–20 weeks | |
Implant | Testosterone | Testopel | Pellet | 150–1,200 mg/3–6 months |
Notes: Men produce about 3 to 11 mg testosterone per day (mean 7 mg/day in young men). Footnotes: a = Never marketed. b = No longer used and/or no longer marketed. Sources: See template. |
References
- Bhasin, S; Brito, JP; Cunningham, GR; Hayes, FJ; Hodis, HN; Matsumoto, AM; Snyder, PJ; Swerdloff, RS; Wu, FC; Yialamas, MA (1 May 2018). "Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 103 (5): 1715–1744. doi:10.1210/jc.2018-00229. PMID 29562364.
- Rivera-Woll, L. M.; Papalia, M.; Davis, S. R.; Burger, H. G. (October 1, 2004). "Androgen insufficiency in women: diagnostic and therapeutic implications". Human Reproduction Update. 10 (5): 421–432. doi:10.1093/humupd/dmh037. PMID 15297435.
- Braunstein, Glenn D (April 1, 2002). "Androgen insufficiency in women: summary of critical issues". Fertility and Sterility. 77: 94–99. doi:10.1016/S0015-0282(02)02962-X. PMID 12007911.
- Braunstein, Glenn D. (July 1, 2006). "Androgen insufficiency in women". Growth Hormone & IGF Research. 16: 109–117. doi:10.1016/j.ghir.2006.03.009. PMID 16631401.
- Tan, RS (July 2005). "Testosterone replacement therapy for female androgen insufficiency syndrome". International Journal of Pharmaceutical Compounding. 9 (4): 259–64. PMID 23925049.
- Davison, Sonia L; Davis, Susan R (June 1, 2003). "Androgens in women". The Journal of Steroid Biochemistry and Molecular Biology. 85 (2): 363–366. doi:10.1016/S0960-0760(03)00204-8. PMID 12943723. S2CID 8048483.
- Guay, A; Traish, A (October 2010). "Testosterone therapy in women with androgen deficiency: Its time has come". Current Opinion in Investigational Drugs. 11 (10): 1116–26. PMID 20872314. S2CID 24910370.
- Guay, A.; Munarriz, R.; Jacobson, J.; Talakoub, L.; Traish, A.; Quirk, F.; Goldstein, I.; Spark, R. (April 24, 2004). "Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part A. Serum androgen levels in women aged 20–49 years with no complaints of sexual dysfunction". International Journal of Impotence Research. 16 (2): 112–120. doi:10.1038/sj.ijir.3901178. PMID 14999217. S2CID 22139942.
- Needham, Merrilee, and Frank Mastaglia, 'Endocrine myopathies', in David Hilton-Jones, and Martin R. Turner (eds), Oxford Textbook of Neuromuscular Disorders, Ch. 38 Endocrine myopathies. Oxford Textbooks in Clinical Neurology (Oxford, 2014; online edn, Oxford Academic, 1 May 2014), doi:10.1093/med/9780199698073.003.0034. Retrieved 29 May 2023.
- Orrell, R W; Woodrow, D F; Barrett, M C; Press, M; Dick, D J; Rowe, R C; Lane, R J (August 1995). "Testosterone deficiency myopathy". Journal of the Royal Society of Medicine. 88 (8): 454–456. ISSN 0141-0768. PMC 1295300. PMID 7562829.
- Haq, T.; Pathan, M. F.; Ikhtaire, S. (January 2016). "Hypogonadotropic Hypogonadism in a Boy with Myopathy". Mymensingh Medical Journal: MMJ. 25 (1): 186–189. ISSN 1022-4742. PMID 26931274.
- Jakiel G, Baran A (2005). "[Androgen deficiency in women]". Endokrynologia Polska (in Polish). 56 (6): 1016–20. PMID 16821229.
- Bachmann GA (April 2002). "The hypoandrogenic woman: pathophysiologic overview". Fertility and Sterility. 77 (Suppl 4): S72–6. doi:10.1016/S0015-0282(02)03003-0. PMID 12007907.
- Bremner WJ (27 May 2003). Androgens in Health and Disease. Humana Press. pp. 365–379. ISBN 978-1-58829-029-8. Retrieved 11 June 2012.
- Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH, Rosner W, Santoro N (October 2014). "Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline". The Journal of Clinical Endocrinology and Metabolism. 99 (10): 3489–510. doi:10.1210/jc.2014-2260. PMID 25279570.
- Staff (3 March 2015). "Testosterone Products: Drug Safety Communication — FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke". FDA. Retrieved 5 March 2015.