MANAGEMENT OF ENDOCRINE DISEASE: Rationale and current evidence for testosterone therapy in the management of obesity and its complications

Abstract

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (T) therapy. As obese men often display lower serum T levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase of T prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low T predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low T are truly hypogonadal. We further describe the mechanisms underlying the bidirectional relationships of T levels with obesity and metabolic health, and finally assess the evidence for T therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum SHBG and total T levels are highly prevalent in obese men, but that only those with low free T levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low T is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound T therapy trials having shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate T therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, focus should remain on lifestyle measures and management of obesity-related consequences.

Prader–Willi Syndrome and Hypogonadism: A Review Article

“…We therefore suggest prescribing the same adult starting dose of testosterone to men with PWS and personalising the maintenance dose as in normal men with hypogonadism. In some men with visceral obesity, it might be better to monitor free testosterone levels during treatment for tailoring treatment [36]. In adolescents and women who are potentially fertile (e.g., inhibin B levels above 20 pg/mL), contraceptive measures should be taken; we prescribe an oral contraceptive pill in these cases.…”

“…In obese men, sex hormone-binding globulin (SHBG) and resultant testosterone levels can be low. Therefore, it is recommended to also measure free testosterone levels and SHBG in order to decide whether free testosterone should be measured to monitor and tailor therapy [36]. Haemoglobin levels should also be monitored as there is a risk of erythrocytosis when testosterone levels are too high.…”

Endocrine Disorders Accompanying Obesity - Effect or Cause?

“…Accordingly, several cross-sectional and longitudinal studies have reported an inverse correlation between serum testosterone level and indices of obesity and metabolic risk [reviewed in ref. 51]. In turn, interventional studies have shown a beneficial effect of testosterone replacement therapy on BMI, adipose tissue distribution, and body composition in hypogonadal men [14].…”

Testosterone replacement therapy and its relationship with hyperestrogenism and obesity. Problems of laboratory diagnostics of hyperestrogenism

“…Кроме того, на фоне статей, подтверждающих эффективность ТЗТ, есть убедительные работы, которые акцентируют внимание на негативных сторонах ТЗТ и обосновывают свою позицию [21,22]. Прежде всего важно модифицировать образ жизни и мотивировать пациента к снижению объема жировой ткани, так как без этих важнейших действий можно не добиться никакого эффекта даже при использовании максимально успешных препаратов [23]. Тестостерон не является конечной точкой в стероидогенезе.…”