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Seminars in Reproductive Endocrinology 1998There is increasing interest in the use of menopausal androgen replacement therapy (MART) in symptomatic women undergoing natural or surgical menopause. However, the... (Review)
Review
There is increasing interest in the use of menopausal androgen replacement therapy (MART) in symptomatic women undergoing natural or surgical menopause. However, the efficacy of MART in alleviating these symptoms compared to traditional estrogen/progestin hormone replacement therapy remains a subject of debate. Accordingly, attention must be focused on the side-effects of the various MART preparations. The dose, alkylation, and route of administration of these compounds influences the development of side effects. While all androgens are potential virilizing agents, alkylated compounds have an additional risk of inducing severe hepatic consequences, regardless of their route of administration. Fortunately, the lower doses administered to women compared to men has not resulted in significant hepatic events. Generation of an adverse lipoprotein profile is possible but is not addressed in this article. Thus, virilizing and cutaneous side effects remain the primary concern. While some observational studies indicate acne and/or hirsutism are evident in up to 38% and 36% of oral methyltestosterone-treated patients, respectively, other studies performed in a prospective fashion suggest a much lower incidence of approximately 5%. Other reported virilizing effects include deepening of the voice and clitoromegaly. Additional concerns are related to risks of developing endometrial hyperplasia when MART is used in conjunction with estrogens. Fortunately, concomitant progestin administration is protective. Finally, there is a theoretical concern that MART may increase the risk of developing breast cancer but this has not been demonstrated in clinical practice. Overall, the safety profile of MART appears to be acceptable when dosing avoids supraphysiologic testosterone levels.
Topics: Acne Vulgaris; Adult; Androgens; Breast Neoplasms; Dose-Response Relationship, Drug; Endometrium; Estrogen Replacement Therapy; Female; Humans; Hyperplasia; Menopause; Middle Aged; Virilism
PubMed: 9711680
DOI: 10.1055/s-2007-1016265 -
Obstetrics and Gynecology Nov 2002The androgen source in women with hirsutism and signs of virilism may be the ovary or adrenal gland.
BACKGROUND
The androgen source in women with hirsutism and signs of virilism may be the ovary or adrenal gland.
CASES
Three patients with androgen excess are reported. Two had hyperandrogenemia and Cushing syndrome with an adrenal mass greater than 5.5 cm; the third had a small adrenal adenoma secreting only testosterone and responsive to human chorionic gonadotropin. In all cases, the pathologic report from surgery and the long-term resolution of symptoms confirmed the benign nature of the tumors.
CONCLUSION
Basal and dynamic hormonal tests cannot precisely differentiate ovarian from adrenal tumors. Adrenal adenomas must be considered as a cause of hyperandrogenic syndrome.
Topics: Adrenal Cortex Function Tests; Adrenal Cortex Neoplasms; Adrenocortical Adenoma; Adult; Androgens; Cushing Syndrome; Female; Hirsutism; Humans; Hyperandrogenism; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Testosterone; Virilism
PubMed: 12423821
DOI: 10.1016/s0029-7844(02)02098-7 -
Journal of Drugs in Dermatology : JDD Feb 20135α-reductase (5α-R) isozymes are ubiquitously expressed in human tissues. This enzyme family is composed of 3 members that perform several important biologic... (Review)
Review
5α-reductase (5α-R) isozymes are ubiquitously expressed in human tissues. This enzyme family is composed of 3 members that perform several important biologic functions. 5α-R isozymes play an important role in benign prostate hyperplasia, prostate cancer, and androgen-stimulated skin disorders, which include androgenic alopecia, acne, and hirsutism. Discovery of 5α-R type 2 deficiency in 1974 sparked interest in development of pharmaceutical agents to inhibit 5α-R isozymes, and 2 such inhibitors are currently available for clinical use: finasteride and dutasteride. 5α-R inhibitors are US Food and Drug Administration (FDA)-approved for the treatment of benign prostate hyperplasia. Only finasteride is FDA-approved for treatment of male androgenic alopecia. This article reviews the pathophysiology of androgen-stimulated skin disorders and the key clinical trials using 5α-R inhibitors in the treatment of androgen-stimulated skin disorders.
Topics: 5-alpha Reductase Inhibitors; Acne Vulgaris; Alopecia; Androgen Antagonists; Androgens; Female; Hirsutism; Humans; Male; Skin; Skin Diseases
PubMed: 23377402
DOI: No ID Found -
Journal of the American Academy of... Jun 1993In the May 1993 issue of the Journal we reviewed the basic science of androgen biology in women. We now discuss the evaluation of suspected hyperandrogenism and the... (Review)
Review
In the May 1993 issue of the Journal we reviewed the basic science of androgen biology in women. We now discuss the evaluation of suspected hyperandrogenism and the therapeutic modalities available.
Topics: Adrenal Hyperplasia, Congenital; Androgen Antagonists; Androgens; Contraceptives, Oral; Cushing Syndrome; Female; Hirsutism; Humans; Leuprolide; Polycystic Ovary Syndrome; Reference Values; Virilism
PubMed: 8496453
DOI: 10.1016/0190-9622(93)70129-h -
Climacteric : the Journal of the... Apr 2022Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from the adrenal glands and/or ovaries clinically manifested by the...
Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from the adrenal glands and/or ovaries clinically manifested by the presence of terminal hair in androgen-dependent areas of the body, and other manifestations of hyperandrogenism such as acne and alopecia or the development of virilization. In such circumstances, physicians must exclude the possibility of rare but serious androgen-producing tumors of the adrenal glands or ovaries. Worsening of undiagnosed hyperandrogenic disorders such as polycystic ovary syndrome, congenital adrenal hyperplasia, ovarian hyperthecosis, Cushing syndrome and iatrogenic hyperandrogenism should be considered for differential diagnosis. Elevated serum testosterone not only causes virilizing effects, but also will lead to hypercholesterolemia, insulin resistance, hypertension and cardiac disease. An ovarian androgen-secreting tumor, which is diagnosed in 1-3 of 1000 patients presenting with hirsutism, comprises less than 0.5% of all ovarian tumors. Adrenal tumors, including non-malignant adenomas and malignant carcinomas, are less common than ovarian tumors but cause postmenopausal virilization. Measurement of serum testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, androstenedione and inhibin B is necessary in postmenopausal women with the complaints and signs of hyperandrogenism. Some tests to discard Cushing syndrome should also be done. After an etiological source of androgen hypersecretion has been suspected, we recommend performing magnetic resonance imaging of the adrenal glands or ovaries. Medical management with gonadotropin-releasing hormone agonist/analogues or antagonists has been reported for women who are either unfit for surgery or in whom the source of elevated testosterone is unidentified.
Topics: Androgens; Cushing Syndrome; Female; Humans; Hyperandrogenism; Male; Ovarian Neoplasms; Polycystic Ovary Syndrome; Postmenopause; Testosterone; Virilism
PubMed: 33988479
DOI: 10.1080/13697137.2021.1915273 -
The Journal of Investigative... Dec 2005The pilosebaceous unit (PSU) response to androgen is variable. Certain population of PSU respond to androgen in a distinctive pattern that results in sexual hair... (Review)
Review
The pilosebaceous unit (PSU) response to androgen is variable. Certain population of PSU respond to androgen in a distinctive pattern that results in sexual hair development in some, sebaceous gland development in others. Furthermore, androgen excess is variably manifest in women as hirsutism, acne vulgaris, seborrhea, or pattern alopecia. Although sebaceous cells act as intracrine cells, activating pro-hormones to potent androgens that act within the sebocyte, hair follicle metabolism predominantly inactivates testosterone. Androgen action in the sexual hair follicle appears to be mediated by the dermal papilla and possibly, by inducing expression of a specific keratin, hHa7, in the hair medulla. The data do not clearly support a relationship between idiopathic hirsutism, the hirsutism that occurs in the absence of androgen excess, and variations in androgen mechanism of action. Androgens are prominent among the hormones that modulate the biological mechanism regulating the hair cycle. However, the basis for the variable pattern of PSU response to androgen is unclear, as is the basis for the variable development of hirsutism in response to androgen excess and the incomplete reversal of hirsutism by anti-androgen treatment. Improved treatment of hirsutism awaits improved understanding of the nature of the interaction between androgens and other determinants of hair follicle biology.
Topics: Androgens; Female; Hair; Hair Follicle; Hirsutism; Hormones; Humans; Male; Sebaceous Glands; Sex Characteristics
PubMed: 16382665
DOI: 10.1111/j.1087-0024.2005.10106.x -
Endocrinology Jan 2023Androgens are steroid hormones crucial for sexual differentiation of the brain and reproductive function. In excess, however, androgens may decrease fertility as...
Androgens are steroid hormones crucial for sexual differentiation of the brain and reproductive function. In excess, however, androgens may decrease fertility as observed in polycystic ovary syndrome, a common endocrine disorder characterized by oligo/anovulation and/or polycystic ovaries. Hyperandrogenism may also disrupt energy homeostasis, inducing higher central adiposity, insulin resistance, and glucose intolerance, which may exacerbate reproductive dysfunction. Androgens bind to androgen receptors (ARs), which are expressed in many reproductive and metabolic tissues, including brain sites that regulate the hypothalamo-pituitary-gonadal axis and energy homeostasis. The neuronal populations affected by androgen excess, however, have not been defined. We and others have shown that, in mice, AR is highly expressed in leptin receptor (LepRb) neurons, particularly in the arcuate (ARH) and the ventral premammillary nuclei (PMv). Here, we assessed if LepRb neurons, which are critical in the central regulation of energy homeostasis and exert permissive actions on puberty and fertility, have a role in the pathogenesis of female hyperandrogenism. Prenatally androgenized (PNA) mice lacking AR in LepRb cells (LepRbΔAR) show no changes in body mass, body composition, glucose homeostasis, or sexual maturation. They do show, however, a remarkable improvement of estrous cycles combined with normalization of ovary morphology compared to PNA controls. Our findings indicate that the prenatal androgenization effects on adult reproductive physiology (ie, anestrus and anovulation) are mediated by a subpopulation of LepRb neurons directly sensitive to androgens. They also suggest that the effects of hyperandrogenism on sexual maturation and reproductive function in adult females are controlled by distinct neural circuits.
Topics: Pregnancy; Humans; Mice; Female; Animals; Receptors, Androgen; Hyperandrogenism; Receptors, Leptin; Anovulation; Sexual Maturation; Androgens; Polycystic Ovary Syndrome; Virilism; Estrous Cycle
PubMed: 36683455
DOI: 10.1210/endocr/bqad015 -
Clinics in Endocrinology and Metabolism May 1986The growth of hair, except that on the scalp, and the secretion of sebum are, in general, under the major influence of androgens. However, the responses of the hair... (Review)
Review
The growth of hair, except that on the scalp, and the secretion of sebum are, in general, under the major influence of androgens. However, the responses of the hair follicles and their associated glands vary greatly between sites and between individuals. On the face, trunk and extremities the most important role of testosterone is to increase the period of activity, the anagen phase, of the hair follicle, though it also increases the rate of growth, thickness, extent of medullation and pigmentation of the hair. These effects involve high levels of hormone and its conversion to 5 alpha-dihydrotestosterone in the target organ. In contrast, the lower pubic triangle develops luxuriantly even in absence of 5 alpha-reductase. In the sebaceous glands, cell replication and lipid synthesis do not seem to be identically controlled, since they respond differently to inhibitors. The response of the sebaceous glands to androgens involves the interaction at the target site of pituitary factors, for which growth hormone, prolactin, and melanocyte stimulating hormone are all putative candidates. The most important scientific and clinical question is whether, in any particular circumstances, the degree of response of the hair follicles or sebaceous glands is determined by the level of available androgen or by the sensitivity of the target organ. While it is true that some patients with hirsutism or acne have above normal levels of plasma androgens or below normal levels of SHBG, a substantial proportion are normal in all respects. Moreover, the rates of hair growth on the extremities or of sebum excretion on the forehead do not seem to be correlated either positively with plasma androgens or negatively with SHBG, though they each have been shown to be correlated with circulating 5 alpha-dihydrotestosterone. The conclusion must be that, although male-type hair growth and high sebaceous secretion may be caused by, or at least accompanied by, high levels of free testosterone, the critical factor is more likely to be the peripheral response.
Topics: Adult; Androgens; Axilla; Dihydrotestosterone; Female; Genitalia; Hair; Hirsutism; Humans; Male; Pituitary Hormones; Scalp; Sebaceous Glands
PubMed: 3521958
DOI: 10.1016/s0300-595x(86)80028-7 -
British Journal of Haematology Jun 2020Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood...
Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
Topics: Adolescent; Adult; Androgens; Bone Marrow Failure Disorders; Canada; Cell Lineage; Child; Child, Preschool; Combined Modality Therapy; Danazol; Disease Progression; Drug Substitution; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Middle Aged; Oxymetholone; Pancytopenia; Registries; Thrombocytopenia; Treatment Outcome; Virilism
PubMed: 32128787
DOI: 10.1111/bjh.16445 -
Frontiers in Endocrinology 2023Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, typically characterised by high circulating androgen levels, oligo- or anovulation,...
INTRODUCTION
Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, typically characterised by high circulating androgen levels, oligo- or anovulation, and polycystic ovarian morphology. Sexual dysfunction, including decreased sexual desire and increased sexual dissatisfaction, is also reported by women with PCOS. The origins of these sexual difficulties remain largely unidentified. To investigate potential biological origins of sexual dysfunction in PCOS patients, we asked whether the well-characterized, prenatally androgenized (PNA) mouse model of PCOS exhibits modified sex behaviours and whether central brain circuits associated with female sex behaviour are differentially regulated. As a male equivalent of PCOS is reported in the brothers of women with PCOS, we also investigated the impact of maternal androgen excess on the sex behaviour of male siblings.
METHODS
Adult male and female offspring of dams exposed to dihydrotestosterone (PNAM/PNAF) or an oil vehicle (VEH) from gestational days 16 to 18 were tested for a suite of sex-specific behaviours.
RESULTS
PNAM showed a reduction in their mounting capabilities, however, most of PNAM where able to reach ejaculation by the end of the test similar to the VEH control males. In contrast, PNAF exhibited a significant impairment in the female-typical sexual behaviour, lordosis. Interestingly, while neuronal activation was largely similar between PNAF and VEH females, impaired lordosis behaviour in PNAF was unexpectedly associated with decreased neuronal activation in the dorsomedial hypothalamic nucleus (DMH).
CONCLUSION
Taken together, these data link prenatal androgen exposure that drives a PCOS-like phenotype with altered sexual behaviours in both sexes.
Topics: Female; Male; Pregnancy; Humans; Animals; Mice; Polycystic Ovary Syndrome; Androgens; Lordosis; Siblings; Virilism
PubMed: 36875467
DOI: 10.3389/fendo.2023.1116482