Effects of Testosterone Therapy on Cardiovascular Risk Markers in Androgen-Deficient Women with Hypopituitarism

Miller, Karen K.; Biller, Beverly M. K.; Schaub, Amber E.; Pulaski-Liebert, Karen J.; Bradwin, Gary; Rifai, Nader; Klibanski, Anne

doi:10.1210/jc.2007-0195

Cited by 31 publications

(16 citation statements)

References 40 publications

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“…4b), as measured by cross-sectional computed tomography scan, with no effect on fat mass or body weight compared with placebo [68] in women with hypopituitarism. There was no deterioration in insulin resistance or deleterious effect on lipids, lipoproteins or high-sensitivity C-reactive protein levels [69]. These data suggest that, despite the fact that endogenous androgen levels are relatively very low in women compared to men, they may play an important role in the maintenance of muscle mass in women, but further studies are needed to investigate this hypothesis.…”

Section: Effects Of Androgen Deficiency and Testosterone Administratimentioning

confidence: 76%

Androgen deficiency: effects on body composition

Miller

2008

Pituitary

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Published data on the effects of androgen deficiency and testosterone administration on body composition in men and women are reviewed. In experimental paradigms, androgen deprivation decreases lean body mass and increases fat mass in men, and physiologic replacement reverses these abnormalities. The anabolic effects of testosterone administration on muscle in men are well-established, and current understanding of the underlying mechanisms are discussed. Randomized, placebo-controlled studies have been performed to investigate the effects of testosterone administration on body composition in a number of male hypogonadal states, including HIV-associated weight loss, supraphysiologic glucocorticoid administration, aging and obesity, with variable outcomes, and the results are reviewed. There are few data investigating the effects of hypoandrogenemia or androgen replacement on body composition in women, in whom endogenous testosterone levels are a fraction of those in men. A recent randomized, placebo-controlled study of physiologic testosterone replacement therapy in women with profound hypoandrogenemia due to hypopituitarism demonstrated an increase in skeletal muscle mass but no change in body fat. Further research is needed to establish the effects of endogenous androgens on the regulation of body composition in women.

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Section: Effects Of Androgen Deficiency and Testosterone Administratimentioning

confidence: 76%

Androgen deficiency: effects on body composition

Miller

2008

Pituitary

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“…A similar but slightly weaker Ca-dependent vasorelaxant effect of E 2 was noted in rat aorta after phenylephrine precontraction (20). Chronic low-dose T administration improved the risk of myocardial ischemia (21), lipid profile, and insulin resistance because of its direct vasoactive and metabolic effects (22). Despite progressive atherosclerosis, chronic T treatment enhanced Ach-dependent, endothelium-dependent relaxation in ovariectomized female monkeys, although it did not influence direct smooth muscle-dependent relaxation elicited by sodium nitroprusside (23).…”

Section: Sara Vascular Insulin Resistance In Pcos Fertil Steril 2012mentioning

confidence: 99%

Arteriolar insulin resistance in a rat model of polycystic ovary syndrome

Sára

Péter

Masszi

et al. 2012

Fertility and Sterility

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Objective: To investigate the vascular dysfunction caused by insulin resistance in polycystic ovary syndrome (PCOS) and the effectiveness of vitamin D in an animal model. Design: Controlled experimental animal study. Setting: Animal laboratory at a university research institute. Animal(s): Thirty female Wistar rats. Intervention(s): Rats were divided into groups at age 21-28 weeks. Twenty of them were subjected to dihydrotestosterone (DHT) treatment (83 mg/d); ten of them also received parallel vitamin D treatment (120 ng/100 g/wk). Oral glucose tolerance tests with insulin level measurements were performed. Gracilis arterioles were tested for their contractility as well as their nitric oxide (NO)-dependent and insulin-induced dilation using pressure arteriography. Main Outcome Measure(s): Several physiologic parameters, glucose metabolism, and pressure arteriography. Result(s): DHT treatment increased the passive diameter of resistance arterioles, lowered norepinephrine-induced contraction (30.1 AE 4.7% vs. 8.7 AE 3.6%) and reduced acetylcholine-induced (122.0 AE 2.9% vs. 48.0 AE 1.4%) and insulin-induced (at 30 mU/mL: 21.7 AE 5.3 vs. 9.8 AE 5.6%) dilation. Vitamin D treatment restored insulin relaxation and norepinephrine-induced contractility; in contrast, it failed to alter NO-dependent relaxation.

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“…However, it is important to note that physiological testosterone replacement in women of reproductive age with severe androgen deficiency secondary to hypopituitarism resulted in possible minor improvements in indirect measures of insulin action (fasting insulin, HOMA-IR, QUICKI) after 12 months of therapy [39], suggesting that testosterone replacement in androgen-deficient premenopausal women is not deleterious. Further long-term studies of the effects of physiologic testosterone therapy on insulin sensitivity in this population are warranted, preferably utilizing the euglycemic hyperinsulinemic clamp technique.…”

Section: Effects Of Androgen Administration In Womenmentioning

confidence: 99%

Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome?

Corbould

2008

Diabetes Metabolism Res

120

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Hyperinsulinemia as a consequence of insulin resistance causes hyperandrogenemia in women. The objective was to review evidence for the converse situation, i.e. whether androgens adversely influence insulin action. Androgen excess could potentially contribute to the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS), metabolic syndrome/type 2 diabetes, and in obese peripubertal girls. An Entrez-PubMed search was conducted to identify studies addressing the relationship of androgens with metabolic syndrome/type 2 diabetes in women. Studies reporting outcomes of androgen administration, interventions to reduce androgen effects in hyperandrogenemic women, and basic studies investigating androgen effects on insulin target tissues were reviewed. Multiple studies showed associations between serum testosterone and insulin resistance or metabolic syndrome/type 2 diabetes risk in women, but their cross-sectional nature did not allow conclusions about causality. Androgen administration to healthy women was associated with development of insulin resistance. Intervention studies in women with hyperandrogenism were limited by small subject numbers and use of indirect methods for assessing insulin sensitivity. However, in three of the seven studies using euglycemic hyperinsulinemic clamps, reduction of androgen levels or blockade of androgen action improved insulin sensitivity. Testosterone administration to female rats caused skeletal muscle insulin resistance. Testosterone induced insulin resistance in adipocytes of women in vitro. In conclusion, the metabolic consequences of androgen excess in women have been under-researched. Studies of long-term interventions that lower androgen levels or block androgen effects in young women with hyperandrogenism are needed to determine whether these might protect against metabolic syndrome/type 2 diabetes in later life.

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Effects of Testosterone Therapy on Cardiovascular Risk Markers in Androgen-Deficient Women with Hypopituitarism

Cited by 31 publications

References 40 publications

Androgen deficiency: effects on body composition

Androgen deficiency: effects on body composition

Arteriolar insulin resistance in a rat model of polycystic ovary syndrome

Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome?

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