Androgens

Anthony Westward. Norman Ph.D. , Helen L. Henry Ph.D. , in Hormones (Third Edition), 2015

F Androgens in Females

Androgens play important roles in the reproductive functions of females. As indicated in Chapter 2 and discussed again in Affiliate 13, testosterone and androstenedione are the substrates for aromatase and obligatory intermediates in the production of estradiol and estrone, respectively. Adrenal androgens play a critical office in female person puberty bringing nearly the changes in pubic and axillary hair; the onset of these effects is termed the adrenarche, the adrenal analogue of the menarche, which is driven by the ovary. Excessive exposure to androgens during uterine life can bring nearly masculinization of a female person fetus, depending on the timing and extent of the exposure. Backlog androgens at any point in adult life tin have masculinizing effects on the female, manifested every bit excess hair growth, vocalisation changes and changes in body composition.

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Female Reproduction

Carlos Stocco , in Encyclopedia of Reproduction (Second Edition), 2018

Office of Androgens in Folliculogenesis

Currently, it is widely accepted that androgen actions change from stimulation to inhibition equally follicles mature. Moreover, it has been suggested that inappropriately high levels of androgens promote follicular atresia. Here, we will briefly describe known effects of androgens throughout folliculogenesis.

Primordial Follicles

Androgens promote the initiation of primordial follicle growth in mice, sheep, and primates. Notwithstanding, it has been shown that primordial human follicles do not express the AR. Therefore, information technology is expected that this effect of androgen is indirect via androgen activation of primary and secondary follicles, which in turn produce factors, such as IGF1, that stimulate primordial follicle activation.

Preantral and Early Antral Follicle

In primates, bovines, and rodents, androgens promote early follicle growth. In vitro findings demonstrated that testosterone and DHT meliorate the survival of preantral follicles in primates. In rhesus monkeys, DHT rescues follicle growth after handling with drugs that inhibit steroid synthesis. In rhesus monkeys, high levels of AR mRNA correlate with elevated levels of granulosa cell proliferation and the absence of apoptotic jail cell expiry in these same follicles. In contrast, low or undetectable levels of AR mRNA are associated with barely detectable proliferation but abundant apoptotic cell death ( Weil et al., 1998). Testosterone stimulates the main to secondary follicle transition in fetal bovine ovaries, an outcome that is inhibited by antagonists of the AR. Also in bovines, testosterone promotes the growth of follicles, whereas estradiol has no furnishings, suggesting that the result of testosterone is not due to its conversion to estradiol. Recent findings in rats demonstrated that DHT promotes follicle growth in a stage-dependent manner via changes in granulosa cell proliferation and apoptosis. Thus, androgen stimulation of preantral follicles increases rat granulosa prison cell proliferation and decreases apoptosis. The combination of these effects augments follicular growth. Yet, androgens effects on follicle growth and antrum formation seem to follow a biphasic blueprint. Thus, low levels of androgens induce follicle maturation, while high levels inhibit oocyte maturation and follicle growth (Lebbe et al., 2017).

Large Antral to Preovulatory Follicles

At the antral stage, androgens may have positive or adverse effects on follicular growth ( Fig. 2). In rat granulosa cells of antral follicles, androgens broaden the stimulatory effect of FSH on estradiol, aromatase, and plasminogen expression. On the other mitt, androgens increase follicular atresia and inhibit FSH-induced granulosa cell proliferation in antral follicles. Moreover, in primates, it has been shown that DHT inhibits the product of estradiol, which is exclusively produced by antral follicles. Strikingly, AR antagonists can amplify the stimulatory effects of FSH and LH, suggesting that endogenous androgens block gonadotropin-stimulated ovulation. In fact, in primates, high concentrations of DHT are antagonistic to gonadotropin-stimulated ovarian function. The mechanisms involved in these differential effects of androgens during folliculogenesis remain to be determined.

Fig. 2

Fig. 2. A decrease or an excess of androgens significantly alter the normal progress of folliculogenesis. Run across Fig. i for more details.

Finally, in rhesus monkeys, AR expression increases during the induction of ovulation along with a temporary rise in androstenedione levels in the follicular fluid. This suggests that androgens may also play a role in the periovulatory follicles. In mice defective the AR, treatment with gonadotropins causes an increase in apoptosis in antral follicles (run across succeeding text). These results suggest that the AR plays a significant role in granulosa prison cell survival during the periovulatory stage, and the absenteeism of AR may crusade granulosa cells to be more susceptible to apoptosis.

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Androgens

P.Southward. Rao , in Encyclopedia of Toxicology (Third Edition), 2014

Human

Androgens may have a virilizing effect in women. The undesirable manifestations include acne, growth of facial pilus, and coarsening of the voice. Profound virilization and serious disturbances in the growth and osseous development can occur when androgens are given to children. The chapters of androgens to enhance epiphyseal closure in children may persist for several months after discontinuation of the drug. All androgens should exist used with great intendance in children. Androgens should not exist used during pregnancy since they cross the placenta and cause masculinization of the female fetus. Feminizing furnishings, particularly gynecomastia, can occur in men who receive androgens. The feminizing effects are peculiarly severe in children and men with liver disease.

Water retention due to sodium chloride (common salt) is a mutual manifestation that leads to weight gain. Edema is also institute in patients with cardiac heart failure, renal insufficiency, liver cirrhosis, and hypoproteinemia. When large doses are used to treat neoplastic diseases, compounds with 17-alkyl substitutions can cause cholestatic hepatitis; at high doses, jaundice is the almost common clinical feature with accumulation of bile in the bile capillaries. Jaundice normally develops later on 2–5 months of therapy. It can be detected by increases in plasma aspartate aminotransferase and alkaline phosphatase.

Obstructive sleep apnea (OSA) causes a balmy lowering of blood testosterone concentrations that is rectified by effective continuous positive airway pressure (CPAP) handling. Although testosterone treatment has precipitated OSA and has potential adverse effects on sleep in older men, the prevalence of OSA precipitated by testosterone treatment remains unclear. It appears to exist a rare idiosyncratic reaction among younger hypogonadal men just the risk may be higher amid older men as the background prevalence of OSA rises steeply with age. Hence, screening for OSA by asking well-nigh daytime sleepiness and partner reports of loud and irregular snoring, peculiarly among overweight men with big collar size, is wise for older men starting testosterone treatment although not routinely required for immature men with classical hypogonadism.

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Androgens

Mona Al Mukaddam , Peter J. Snyder , in Osteoporosis (Fourth Edition), 2013

Effect of Testosterone on Bone in Women with Panhypopituitarism

Because serum testosterone in women comes from direct secretion past the ovaries and adrenal glands and by peripheral conversion of weak adrenal androgens, panhypopituitarism leads to loss of testosterone from both sources and therefore to a greater degree of testosterone deficiency than other clinical conditions. In a study of women with hypopituitarism who were compared to women with normal pituitary function, the women with hypopituitarism had much lower serum testosterone concentrations, using an assay of appropriate sensitivity, even when matched for age and estrogen replacement status [44]. When 53 women with pituitary disease leading to hypoadrenalism and/or hypogonadism were randomized to receive either testosterone or placebo transdermally for 1 year, the mean serum free testosterone concentrations of the women treated with testosterone were maintained within the normal range, merely the concentrations of the women treated with placebo remained subnormal [45]. BMD of the radius and hip, but not the spine, was significantly greater at the finish of the yr'due south treatment in the testosterone-treated grouping than in the placebo-treated group. The differences, even when statistically significant, were relatively small. The alter from baseline to 1 yr in BMD in the hip was 0.9% in the testosterone-treated group and −one.two% in the placebo-treated group, and the change in the radius was 0.8% in the testosterone-treated grouping and −0.5% in the placebo-treated group. In dissimilarity, in hypogonadal men, testosterone has a greater upshot in the first few years of treatment on BMD in the spine than in the hip or radius, and so the results in these women are hard to interpret.

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Androgens

Kay Marshall , in xPharm: The Comprehensive Pharmacology Reference, 2007

Introduction

The male person gonads (more than precisely, the interstitial cells or the cells of Leydig in the testes) and, to a lesser extent, the adrenal cortex (secretes androstenedione and dehydroepiandrosterone that are converted in the periphery to testosterone or estrogen) produce the male sex steroids known as androgens, the secretion of which is controlled by the hypothalamic-pituitary-testicular centrality. The hypothalamus secretes gonadotrophin-releasing hormone (GnRH), which is sometimes referred to every bit luteinizing hormone-releasing hormone (LHRH), and this in turn stimulates the release of the gonadotrophins (follicle-stimulating hormone and luteinizing hormone; sometimes referred to as interstitial cell stimulating hormone in the male), which control gonadal function, including steroidogenesis. Testosterone levels then influence the hypothalamic-pituitary-testicular axis by ways of a negative feedback loop. Sex steroids influence the development and maintenance of the organs and tissues, directly and indirectly associated with reproduction. Testosterone is the chief androgenic hormone formed in the interstitial cells of the testes. However, in many of the androgen target tissues, testosterone has to be converted to the more than active dihydrotestosterone, by 5alpha-reductase. Androgens stimulate the development of the male secondary sex activity characteristics, for instance, male body hair distribution and lengthening of the song cords, as well as regulating gonadal role. Androgens also possess anabolic properties (removal of the 19-methyl group may heighten this particular aspect, east.g., nandrolone) equally they increase the retention of nitrogen, sodium calcium, potassium, chloride, and phosphate. This causes an increase in water retention and bone growth. Peel also tends to get more vascular (and less fat), and erythropoiesis is stimulated.

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Hormonal replacement therapy—estrogens+androgens

In Meyler's Side Furnishings of Drugs (Sixteenth Edition), 2016

An estrogen   +   an androgen

This variant on the theme of estrogen replacement therapy has been propagated from various centers for dissimilar reasons [ane,2].

The theoretical starting point is the ascertainment that (specially after oophorectomy) at that place are deficiencies of both testosterone and androstenedione [iii] and from the observation that estrogens alone practice not relieve all menopausal symptoms. While there may well be justification for androgen replacement after oophorectomy, information technology is not clear that nearly of the claims made for utilize of this approach following a natural menopause are sufficiently well founded to justify the risks involved.

Adding an androgen to estrogen replacement therapy in the menopause has been thought to provide supplementary benefit with respect to climacteric symptoms, fatigue, and impaired libido, likewise as favorably affecting muscle mass, skin quality, and os density. Information technology is likewise stated that androgens improve relief of vasomotor symptoms and relieve depression and anxiety when they occur after the menopause in this grouping of patients. Some workers accept concluded that in women who respond to conjugated estrogens with a rise in blood pressure level (non a common response by whatsoever means), this effect could be avoided by the add-on of an androgen. Withal others have asserted that when the hematocrit falls during estrogen therapy, the effect tin can be prevented by an androgen.

The main reason for caution with the utilize of androgens is the susceptibility of menopausal women to their virilizing effects, which can sometimes prove irreversible. Deepening of the vocalism, hirsutism, and acne can occur in many patients at an early on stage of treatment and can prove pitiful. There may be enlargement of the clitoris, although not consistently.

Yet, there are other reasons for caution. Statements with respect to the outcome of estrogen   +   androgen combinations on blood lipids are, for instance, contradictory, depending on the combinations used. If androgens are to be used, the effect on lipoproteins should at all events be monitored [1].

It is doubtful whether one can avoid unwanted androgenic effects by cautious dosing. For example, the published data seem to prove that a desired effect on libido is just probable to occur at androgen doses sufficient to produce serum testosterone concentrations in the virilizing range (over 2   ng/ml), and that fifty-fifty after withdrawal of such doses virilizing concentrations of testosterone are maintained for many months.

Finally, androgens actually appear in some respects to counter the desired effects of estrogens in this patient group. Doppler flowmetry has been used to study the cardiovascular furnishings of adding an androgen to an estrogen in an open, randomized written report in 40 patients over eight months, all of whom were using transdermal estradiol (50   micrograms/day) and cyclic medroxyprogesterone acetate (10   mg/day) [four]. One-half of the subjects then received additional testosterone undecanoate (twoscore   mg/twenty-four hour period). The investigators concluded that while the androgen improved sexual desire and satisfaction and had no event on endometrial thickness, it did in part counteract the beneficial effects of the estrogens on cerebral vascular activity and lipids. The almost notable change was a meaning increase in the pulsatility index of the middle cerebral artery. The androgen likewise resulted in a 10% reduction in HDL cholesterol concentration within 8 months. The authors therefore urged caution in using androgens, at least in the manner used in this study.

Adverse reactions to estrogen   +   androgen therapy include balmy hirsutism and acne [5]. One group of workers, who examined the use of "Estratest" (an esterified combination of estrogen and methyltestosterone), ended that in their experience under five% of women developed acne or facial hirsutism, a frequency like to that experienced when using conjugated estrogens 0.625   mg/day. Women had significantly less nausea with the estrogen   +   androgen treatment than with conjugated estrogen therapy. Cancers, cardiovascular disease, thromboembolism, and liver affliction were stated to be rare among users of the combination. The only agin events exceeding 4% of full reports were baldness, acne, weight gain, and hirsutism [6]. However, much higher rates of complications with such combinations take been reported from other centers [ane].

The evident disadvantage of a fixed combination is that information technology renders it impossible to bear out any fine adjustment of dosages, such as might be called for in the light of the clinical response and agin reactions in a given individual.

All in all, information technology seems very doubtful whether whatever of the supposed benefits of androgen therapy justify the risks involved, except possibly as a transitional measure in those recently oophorectomized women who have acute symptoms of sudden androgen withdrawal.

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Testosterone/Dihydrotestosterone

Yukiko Ogino , ... Taisen Iguchi , in Handbook of Hormones, 2016

Abstract

Androgens are disquisitional steroid hormones that regulate male sexual development and differentiation, including the formation of the reproductive system and maintenance of its function. Androgens are also essential in muscle evolution and psychosexual behavior. Testosterone and dihydrotestosterone act as the predominant androgens in mammals. Androgens mediate their effects through the androgen receptor (AR), a member of the nuclear receptor superfamily. Liganded AR is translocated from cytoplasm to the nucleus and regulates the transcription of androgen-responsive genes. Mutations in the AR result in diseases such as androgen insensitivity syndrome, prostate cancer, Kennedy's affliction, and infertility.

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HORMONES AND GENDER | Male person Sex activity Steroids and Neuronal Excitability

C.A. Frye , 1000.E. Rhodes , in Encyclopedia of Bones Epilepsy Enquiry, 2009

Androgens and the Hippocampus

Androgens can also have profound effects on nonreproductive behaviors that are mediated in role through nonclassic actions in the hippocampus. The hippocampus is an important site of androgen action. Tritiated testosterone is taken upwardly in the hippocampus of rats. Excitability of hippocampal tissue of male mice is altered post-obit castration and in vivo or in vitro androgen administration restores it to levels of intact males. Similarly, castration of rats or vervet monkeys reduces the density of synaptic contacts on dendritic spines of CA1 pyramidal neurons. Administration of androgens that are stiff modulators of ARs, such as testosterone or the nonaromatizable androgen DHT, and androgens that are only weakly agile at ARs similarly reverse the effect of castration. These effects of androgens are not blocked past coadministration of an AR antagonist. The androgen-stimulated increase of hippocampal spine synapse density does not require ARs. Interestingly, the effects of androgens to enhance cerebral function and mood country, processes that are mediated in role past the hippocampus, too exercise not seem to require actions through ARs. Thus, it has been proposed that androgens' mnemonic and/or antianxiety effects may result, at least in part, from androgens' hippocampal neurotrophic responses.

Actions of androgens on the hippocampus are of item interest because maintenance of androgen levels in this region may minimize the risks of neurodegeneration. Patients with Alzheimer's disease, characterized by damage in the hippocampus, have demonstrated a reduction in circulating concentrations of androgens in comparison to normal controls. Androgens too take protective effects in other models of neurodegeneration. Androgen administration reduces prison cell death in the granule cell layer of the hippocampus of male rats following adrenalectomy. Notably, the decrease in cell death post-obit androgen assistants is associated with functional effects likewise. Androgen-administered rats that had less prison cell expiry in the hippocampus performed amend in a hippocampally mediated retentiveness task than did their vehicle-administered counterparts with more than cell decease. Thus, the hippocampus, a brain area involved frequently in partial and predominantly in generalized seizures, may be an of import target of androgens' antiseizure deportment.

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Androgens: Pharmacological Use and Abuse☆

M.G. Byrne , East. Nieschlag , in Reference Module in Neuroscience and Biobehavioral Psychology, 2017

Treatment of Hematological Disorders

Androgens enhance erythropoiesis via indirect stimulation of erythropoietin secretion from renal and extrarenal sources. Androgens as well act straight on the os marrow stem cells to increase crimson blood cell production in response to erythropoietin. They are therefore beneficial for the treatment of anemia due to chronic renal failure, raising hemoglobin levels by approximately 1–2  m/dL in the presence of adequate iron and folate stores. With the availability of recombinant erythropoietin, androgens are now used infrequently for the handling of anemia associated with chronic renal failure, peculiarly in women, due to virilizing side effects. However, erythropoietin is very expensive and androgens tin can be used in combination with lower doses of erythropoietin.

Androgens tin can also exist beneficial to care for patients with aplastic anemia, Fanconi's anemia, hemolytic anemia, and sickle cell anemia, and some anemia secondary to hematological malignancies. Danazol (600–800   mg   twenty-four hours−1) has been used to treat patients with autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura by directly lowering autoantibody titers.

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Pilosebaceous Unit (PSU)

Dianne Deplewski , in Encyclopedia of Hormones, 2003

I Introduction

Androgens play a fundamental role in the development of the pilosebaceous (PSU) in virtually areas of the body. In androgen-sensitive areas earlier puberty, the hair is vellus and the sebaceous glands are pocket-size. In response to increasing levels of androgens, PSUs become big terminal hair follicles (sexual hairs) in sexual hair areas or they become sebaceous follicles (sebaceous glands) in sebaceous areas. Androgens play a role in PSU disorders, namely, hirsutism, pattern alopecia, and acne vulgaris. Withal, information technology is articulate that the pathogenesis of these disorders involves more than androgen.

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