Androgen deficiency

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Androgen deficiency
Other namesHypoandrogenism, androgen deficiency syndrome, men with hypogonadism, [1] testosterone 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]

Contents

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

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]

Androgen replacement therapy formulations and dosages used in men
RouteMedicationMajor brand namesFormDosage
Oral Testosterone a–Tablet400–800 mg/day (in divided doses)
Testosterone undecanoate Andriol, JatenzoCapsule40–80 mg/2–4× day (with meals)
Methyltestosterone bAndroid, Metandren, TestredTablet10–50 mg/day
Fluoxymesterone bHalotestin, Ora-Testryl, UltandrenTablet5–20 mg/day
Metandienone bDianabolTablet5–15 mg/day
Mesterolone bProvironTablet25–150 mg/day
Sublingual Testosterone bTestoralTablet5–10 mg 1–4×/day
Methyltestosterone bMetandren, Oreton MethylTablet10–30 mg/day
Buccal Testosterone StriantTablet30 mg 2×/day
Methyltestosterone bMetandren, Oreton MethylTablet5–25 mg/day
Transdermal Testosterone AndroGel, Testim, TestoGelGel25–125 mg/day
Androderm, AndroPatch, TestoPatchNon-scrotal patch2.5–15 mg/day
TestodermScrotal patch4–6 mg/day
AxironAxillary solution30–120 mg/day
Androstanolone (DHT) AndractimGel100–250 mg/day
Rectal Testosterone Rektandron, TestosteronbSuppository40 mg 2–3×/day
Injection (IM Tooltip intramuscular injection or SC Tooltip subcutaneous injection) Testosterone Andronaq, Sterotate, VirosteroneAqueous suspension10–50 mg 2–3×/week
Testosterone propionate bTestovironOil solution10–50 mg 2–3×/week
Testosterone enanthate DelatestrylOil solution50–250 mg 1x/1–4 weeks
XyostedAuto-injector50–100 mg 1×/week
Testosterone cypionate Depo-TestosteroneOil solution50–250 mg 1x/1–4 weeks
Testosterone isobutyrate Agovirin DepotAqueous suspension50–100 mg 1x/1–2 weeks
Testosterone phenylacetate bPerandren, AndrojectOil solution50–200 mg 1×/3–5 weeks
Mixed testosterone esters Sustanon 100, Sustanon 250Oil solution50–250 mg 1×/2–4 weeks
Testosterone undecanoate Aveed, NebidoOil solution750–1,000 mg 1×/10–14 weeks
Testosterone buciclate a–Aqueous suspension600–1,000 mg 1×/12–20 weeks
Implant Testosterone TestopelPellet150–1,200 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

Related Research Articles

Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormonal signs that puberty has begun. In the United States, girls are considered to have delayed puberty if they lack breast development by age 13 or have not started menstruating by age 15. Boys are considered to have delayed puberty if they lack enlargement of the testicles by age 14. Delayed puberty affects about 2% of adolescents.

Hypogonadism means diminished functional activity of the gonads—the testicles or the ovaries—that may result in diminished production of sex hormones. Low androgen levels are referred to as hypoandrogenism and low estrogen as hypoestrogenism. These are responsible for the observed signs and symptoms in both males and females.

Pubarche refers to the first appearance of pubic hair at puberty. It is one of the earliest physical changes of puberty and can occur independently of complete puberty. It is usually the second sign of puberty, after thelarche in females and gonadarche in males.

Kallmann syndrome (KS) is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypogonadotropic hypogonadism, Kallmann syndrome has the additional symptom of a total lack of sense of smell (anosmia) or a reduced sense of smell. If left untreated, people will have poorly defined secondary sexual characteristics, show signs of hypogonadism, almost invariably are infertile and are at increased risk of developing osteoporosis. A range of other physical symptoms affecting the face, hands and skeletal system can also occur.

Late-onset hypogonadism (LOH) or testosterone deficiency syndrome (TDS) is a term for a condition in older men characterized by measurably low testosterone levels and clinical symptoms mostly of a sexual nature, including decreased desire for mating, fewer spontaneous erections, and erectile dysfunction. It is the result of a gradual drop in testosterone; a steady decline in testosterone levels of about 1% per year can happen and is well documented in both men and women.

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.

<span class="mw-page-title-main">Testosterone cypionate</span> Chemical compound

Testosterone cypionate, sold under the brand name Depo-Testosterone among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men, including hormone therapy for transgender men. It is given by injection into muscle or subcutaneously, once every one to four weeks, depending on clinical indication.

<span class="mw-page-title-main">Mesterolone</span> Chemical compound

Mesterolone, sold under the brand name Proviron among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels. It has also been used to treat male infertility, although this use is controversial. It is taken by mouth.

<span class="mw-page-title-main">Trestolone</span> Chemical compound

Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an experimental androgen/anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and in androgen replacement therapy for low testosterone levels in men but has never been marketed for medical use. It is given as an implant that is placed into fat. As trestolone acetate, an androgen ester and prodrug of trestolone, the medication can also be given by injection into muscle.

Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced. It typically involves the administration of testosterone through injections, skin creams, patches, gels, pills, or subcutaneous pellets. ART is often prescribed to counter the effects of male hypogonadism.

<span class="mw-page-title-main">Endocrine disease</span> Disorders of the endocrine system

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

<span class="mw-page-title-main">Enclomifene</span> Chemical compound

Enclomifene (INNTooltip International Nonproprietary Name), or enclomiphene (USANTooltip United States Adopted Name), a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group, acts by antagonizing the estrogen receptor (ER) in the pituitary gland, which reduces negative feedback by estrogen on the hypothalamic-pituitary-gonadal axis, thereby increasing gonadotropin secretion and hence gonadal production of testosterone. It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene. Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer. Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic. In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men. As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.

Hypergonadism is a condition where there is a hyperfunction of the gonads. It can manifest as precocious puberty, and is caused by abnormally high levels of testosterone or estrogen, crucial hormones for sexual development. In some cases, it may be caused by a tumor, which can be malignant, but is more commonly benign. Anabolic steroids may also be a major cause of high androgen and estrogen functional activity. Other possible causes include head injuries and brain inflammatory diseases. Hypergonadism may contribute to symptoms such as precocious puberty and abnormal facial hair growth in females.

Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism or primary gonadal failure, is a condition which is characterized by hypogonadism which is due to an impaired response of the gonads to the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and in turn a lack of sex steroid production. As compensation and the lack of negative feedback, gonadotropin levels are elevated. Individuals with HH have an intact and functioning hypothalamus and pituitary glands so they are still able to produce FSH and LH. HH may present as either congenital or acquired, but the majority of cases are of the former nature. HH can be treated with hormone replacement therapy.

Hyperestrogenism, hyperestrogenic state, or estrogen excess, is a medical condition characterized by an excessive amount of estrogenic activity in the body.

<span class="mw-page-title-main">Leydig cell hypoplasia</span> Medical condition

Leydig cell hypoplasia (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 individuals with XY chromosomes. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism, hypergonadotropic hypogonadism, reduced or absent puberty, and infertility.

Gonadotropin-releasing hormone (GnRH) insensitivity also known as Isolated gonadotropin-releasing hormone (GnRH)deficiency (IGD) is a rare autosomal recessive genetic and endocrine syndrome which is characterized by inactivating mutations of the gonadotropin-releasing hormone receptor (GnRHR) and thus an insensitivity of the receptor to gonadotropin-releasing hormone (GnRH), resulting in a partial or complete loss of the ability of the gonads to synthesize the sex hormones. The condition manifests itself as isolated hypogonadotropic hypogonadism (IHH), presenting with symptoms such as delayed, reduced, or absent puberty, low or complete lack of libido, and infertility, and is the predominant cause of IHH when it does not present alongside anosmia.

Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis. Hypothalamic disorders result from a deficiency in the release of gonadotropic releasing hormone (GnRH), while pituitary gland disorders are due to a deficiency in the release of gonadotropins from the anterior pituitary. GnRH is the central regulator in reproductive function and sexual development via the HPG axis. GnRH is released by GnRH neurons, which are hypothalamic neuroendocrine cells, into the hypophyseal portal system acting on gonadotrophs in the anterior pituitary. The release of gonadotropins, LH and FSH, act on the gonads for the development and maintenance of proper adult reproductive physiology. LH acts on Leydig cells in the male testes and theca cells in the female. FSH acts on Sertoli cells in the male and follicular cells in the female. Combined this causes the secretion of gonadal sex steroids and the initiation of folliculogenesis and spermatogenesis. The production of sex steroids forms a negative feedback loop acting on both the anterior pituitary and hypothalamus causing a pulsatile secretion of GnRH. GnRH neurons lack sex steroid receptors and mediators such as kisspeptin stimulate GnRH neurons for pulsatile secretion of GnRH.

<span class="mw-page-title-main">Testosterone (medication)</span> Medication and naturally occurring steroid hormone

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be administered through several different routes, including topical gels or patches, nasal sprays, subdermal implants, or tablets dissolved inside the mouth.

Hypergonadotropic hypergonadism is an endocrine situation and subtype of hypergonadism in which both gonadotropin levels and gonadal function, such as sex hormone production, are abnormally high. It can be associated with hyperandrogenism and hyperestrogenism and with gonadal cysts and tumors. It can be caused by medications such as gonadotropins, gonadotropin-releasing hormone agonists, nonsteroidal antiandrogens, and selective estrogen receptor modulators, as well as conditions like human chorionic gonadotropin-secreting tumors, complete androgen insensitivity syndrome, and estrogen insensitivity syndrome.

References

  1. 1 2 3 4 5 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. 1 2 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.
  6. ↑ 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.
  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.
  8. ↑ 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.
  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. PMID   33998653.
  10. 1 2 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. 1 2 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.
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