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][9]}

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.^[10]

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.^[11][12][13]

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.^[14][15][16] As estrogens are synthesized from androgens, symptoms of hypoestrogenism may be present in both sexes in cases of severe androgen deficiency.^[10]

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.^[17]

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.^[18]

Treatment

See also: Testosterone (medication)

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.^[19] The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.^[19]

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Androgen replacement therapy formulations and dosages used in men

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/2–4× 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 1–4×/day
	Methyltestosteroneb	Metandren, Oreton Methyl	Tablet	10–30 mg/day
Buccal	Testosterone	Striant	Tablet	30 mg 2×/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 2–3×/day
Injection (IMTooltip intramuscular injection or SCTooltip subcutaneous injection)	Testosterone	Andronaq, Sterotate, Virosterone	Aqueous suspension	10–50 mg 2–3×/week
	Testosterone propionateb	Testoviron	Oil solution	10–50 mg 2–3×/week
	Testosterone enanthate	Delatestryl	Oil solution	50–250 mg 1x/1–4 weeks
		Xyosted	Auto-injector	50–100 mg 1×/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 1×/3–5 weeks
	Mixed testosterone esters	Sustanon 100, Sustanon 250	Oil solution	50–250 mg 1×/2–4 weeks
	Testosterone undecanoate	Aveed, Nebido	Oil solution	750–1,000 mg 1×/10–14 weeks
	Testosterone buciclatea	–	Aqueous suspension	600–1,000 mg 1×/12–20 weeks
Implant	Testosterone	Testopel	Pellet	150–1,200 mg/3–6 months
Notes: Men produce about 3 to 11 mg of 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.

See also

• Androgen
• Hyperandrogenism
• Hyperestrogenism
• Hypergonadism
• Hypoestrogenism
• Hypogonadism
• Late-onset hypogonadism
• Hormone replacement therapy
• Feminizing hormone therapy

References

1. 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.
2. 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.
3. 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.
4. 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.
5. Tan, RS (July 2005). "Testosterone replacement therapy for female androgen insufficiency syndrome". International Journal of Pharmaceutical Compounding. 9 (4): 259–64. PMID 23925049.
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7. 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.
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9. "Corrigendum to: "Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline"". The Journal of Clinical Endocrinology & Metabolism. 106 (7): e2843. 2021-05-17. doi:10.1210/clinem/dgab306. ISSN 0021-972X.
10. Ponholzer, Anton; Madersbacher, Stephan (May 2009). "Re: Christina Wang, Eberhard Nieschlag, Ronald Swerdloff, et al. Investigation, Treatment, and Monitoring of Late-Onset Hypogonadism in Males: ISA, ISSAM, EAU, EAA, and ASA Recommendations. Eur Urol 2009;55:121–30". European Urology. 55 (5): e92, author reply e93-4. doi:10.1016/j.eururo.2008.11.053. ISSN 0302-2838. PMID 19081175.
11. 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.
12. 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.
13. 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.
14. Jakiel G, Baran A (2005). "[Androgen deficiency in women]". Endokrynologia Polska (in Polish). 56 (6): 1016–20. PMID 16821229.
15. 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.
16. 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.
17. Barratt, Christopher L R; Björndahl, Lars; De Jonge, Christopher J; Lamb, Dolores J; Osorio Martini, Francisco; McLachlan, Robert; Oates, Robert D; van der Poel, Sheryl; St John, Bianca; Sigman, Mark; Sokol, Rebecca; Tournaye, Herman (2017-11-01). "The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance—challenges and future research opportunities". Human Reproduction Update. 23 (6): 660–680. doi:10.1093/humupd/dmx021. ISSN 1355-4786. PMC 5850791. PMID 28981651.
18. 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.
19. 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.