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      Insuficiência androgênica na mulher e potenciais riscos da reposição terapêutica Translated title: Female androgen insufficiency and potencial risks of therapeutic replacement

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          Abstract

          Na mulher, os androgênios decrescem lenta e progressivamente a partir da quarta década e por toda a vida. O declínio dos androgênios pode gerar um estado de deficiência que se manifesta insidiosamente por diminuição da função sexual, bem estar e energia, alterações na composição corporal e perda de massa óssea. Se há história de ooforectomia bilateral, pan-hipopituitarismo, supressão da androgênese adrenal e/ou os níveis séricos de testosterona biodisponível se encontram reduzidos, é provável que estes sinais e sintomas sejam aliviados pela administração criteriosa de androgênios, cuja prática tem se difundido. Nas doses atualmente preconizadas, parece que os benefícios sobre massa óssea, sexualidade e qualidade de vida são alcançados sem importantes efeitos colaterais de virilização. Entretanto, trabalhos bem controlados são necessários para validar a hipótese de que a administração terapêutica de androgênios em mulheres não tem, a longo prazo, repercussões significativas na incidência sobre câncer de mama ou conseqüências metabólicas indesejáveis.

          Translated abstract

          Women in their fourth decade and older experience a decrease in androgen serum levels. This may lead to the clinical syndrome of female androgen insufficiency expressed by insidious tiredness, diminished sense of well-being and libido, alterations in body composition and bone loss. If there is a past history of bilateral oophorectomy, hypopituitarysm, androgen adrenal supression and/or free testosterone serum levels are low, it is probable that these signs and symptoms could be relieved by a discerning androgen administration, which has been largely accepted. When current recommended doses are used, it appears that the benefits regarding bone mass, sexuality and well-being may be achieved without important signs of masculinizing. Nonetheless, it is necessary to conduct well-controlled, long-term studies, in order to validate the hypothesis that therapeutic administration of androgens to women does not lead to an increased incidence of breast cancer or metabolic complications.

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          Most cited references123

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          Aging, body composition, and lifestyle: the Fels Longitudinal Study.

          Changes in body composition in men and women occur with age, but these changes are affected by numerous covariate factors. The study examined patterns of change in body composition and determined the effects of long-term patterns of change in physical activity in older men and women and in menopausal status and estrogen use in women. Serial measures of height, weight, body mass index (BMI), total body fat (BF), percentage BF, and fat-free mass (FFM) from underwater weighing of 102 men and 108 women enrolled in the Fels Longitudinal Study were analyzed. Physical activity levels and menopausal status were included as covariates. There were significant age-related decreases in FFM and height and increases in total BF, percentage BF, weight, and BMI. Physical activity was associated with decreases in total BF, percentage BF, weight, and BMI in men and were associated with increases in FFM and decreases in total BF and percentage BF in women. Postmenopausal women had significantly higher total BF and percentage BF than did pre- and perimenopausal women. The longer the time since menopause the greater were the increases in weight, BMI, total BF, and percentage BF; however, estrogen use attenuated these increases. Low FFM can be improved by increased physical activity. The effects of an intervention program on body composition can be masked if only body weight or BMI is measured. The effects of physical activity were more profound in postmenopausal than in premenopausal women, and estrogen use had beneficial effects on body composition.
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            Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis.

            Aging men develop a significant loss of muscle strength that occurs in conjunction with a decline in serum testosterone concentrations. We investigated the effects of testosterone administration to six healthy men [67 +/- 2 (SE) yr] on skeletal muscle protein synthesis, strength, and the intramuscular insulin-like growth factor I (IGF-I) system. Elderly men with serum testosterone concentrations of 480 ng/dl or less were given testosterone injections for 4 wk to produce serum concentrations equal to those of younger men. During testosterone administration muscle strength (isokinetic dynamometer) increased in both right and left hamstring and quadricep muscles as did the fractional synthetic rate of muscle protein (stable-isotope infusion). Ribonuclease protection assays done on total RNA from muscle showed that testosterone administration increased mRNA concentrations of IGF-I and decreased mRNA concentrations of insulin-like growth factor binding protein-4. We conclude that increasing testosterone concentrations in elderly men increases skeletal muscle protein synthesis and strength. This increase may be mediated by stimulation of the intramuscular IGF-I system.
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              Androgen effects on bone and muscle.

              Bone health and strength are dependent on the coupling of cone resorption and bone formation. This process is governed by the interaction of osteoclasts and osteoblasts plus the modulating influence of the bone mechanicosensory cells-the osteocytes. Both sex steroids-estrogen (E) and testosterone (T)- have receptors on all bone cells, with androgen dominance on osteoblasts and osteocytes. Specific receptors for the weaker androgens, such as DHEA have also been identified. The activity of the sex steroids, influenced by various enzymes found in bone, is reflective of the hormone ligand before its binding to the bone cells. As a result, T acts both directly and via its aromatization to estradiol. The activity of the androgens also varies with the bone surface; periosteal cells, for example, do not have 5alpha-reductase activity, indicating that T is the active metabolite at this clinically important site. Androgens influence bone cell function via local and systemic growth factors and cytokines. By enhancing osteoblast differentiation, androgens regulate bone matrix production, organization, and mineralization. Androgens also regulate osteoclast recruitment and activity. Endogenous androgens increase bone mineral density (BMD) in both adolescent and adult premenopausal women. Women with excess endogenous androgen-for example, those with hirsutism and polycystic ovary syndrome (PCOS)-have increased BMD compared with normal young women. E and androgen therapy increases BMD to a greater degree than does E therapy alone. This is true for both oral combinations of esterified E and methyltestosterone and for subcutaneous T implants. Androgenic progestins have an additive effect on BMD when combined with E therapy and have the further advantage of being protective to the endometrium in E-treated women. Androgens increase muscle mass and strength. The resulting improvement in physical activity leads to the activation of bone-forming sites and the stimulation of the bone formation-modulating cells, the osteocytes. Mechanical loading, when combined with hormone therapy, results in greater osteogenic response than does either alone.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                abem
                Arquivos Brasileiros de Endocrinologia & Metabologia
                Arq Bras Endocrinol Metab
                Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo )
                1677-9487
                April 2005
                : 49
                : 2
                : 205-216
                Affiliations
                [1 ] Universidade Federal do Rio de Janeiro Brazil
                [2 ] Universidade Federal do Rio de Janeiro Brazil
                Article
                S0004-27302005000200006
                10.1590/S0004-27302005000200006
                e158b322-1af0-4c6f-b320-3a38911b7a02

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0004-2730&lng=en
                Categories
                ENDOCRINOLOGY & METABOLISM

                Endocrinology & Diabetes
                Menopause,Androgen insufficiency,Androgen replacement,Menopausa,Insuficiência androgênica,Reposição androgênica

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