Effects of Intermission and Resumption of Long-term Testosterone Replacement Therapy on Body Weight and Metabolic Parameters in Hypogonadal in Middle-aged and Elderly Men

Aksam Yassin; Yousef Almehmadi; Farid Saad; Gheorghe Doros; Louis Gooren


Clin Endocrinol. 2016;84(1):107-114. 

In This Article

Abstract and Introduction


Objective In addition to primary and secondary ('classical') hypogonadism, hypogonadism occurring in middle-aged and elderly men has been recognized. There is evidence that restoring T levels to normal improves body weight, serum lipids and glucose levels.

Design Observational registry study.

Patients Two hundred and sixty-two hypogonadal, middle-aged and elderly, men received testosterone replacement treatment (TRT). After having been on TRT for a mean duration of 65·5 months, TRT was temporarily intermitted in 147 patients for a mean of 16·9 months (Group I) due to cost reimbursement issues and in seven men due to prostate cancer. All these men resumed TRT for a mean period of 14·5 months. Of the cohort, 115 men were treated continuously (designated as Group C). To compare on-treatment to off-treatment periods, three periods of equal duration were defined: pre-intermission (on TRT), during intermission (off TRT) and post-intermission (on TRT after resumption of TRT). For proper comparison, the same periods were analysed for those patients who continued TRT throughout (Group C).

Measurements Variables of body weight, glucose metabolism, lipids, blood pressure and C-reactive protein (CRP).

Results In Group C there was a continuous improvement of body weight, serum lipids, glucose, HbA1c, blood pressure and CRP. In Group I there was a similar initial improvement which was reversed upon intermission of T administration but which appeared again when T treatment was reinstated.

Conclusions Our observation indicates that T administration improves body weight and metabolic factors in men with hypogonadism but withdrawal of T reverses these beneficial effects to appear again when TRT is resumed.


In addition to primary and secondary hypogonadism, hypogonadism based on the decline of serum testosterone (T) levels in some ageing men has received extensive attention over the last decades.[1] The term late-onset hypogonadism (LOH), distinguishing it from primary and secondary hypogonadism, has been proposed to describe this form of hypogonadism.[1] While it was initially thought that chronological age per se was an important determinant of LOH, this did not hold up in later research.[1] A far more important determinant of the decline of T in ageing men is obesity, but also impaired general health.[2] The role of obesity is supported in a study from Russia on serum T levels in obese men <40 years. Their hormonal profiles were not different from obese men labelled as men with LOH.[3] The role of obesity is supported by the reversibility of low T levels by weight loss.[1,2] Over time, there have been increasingly indications that the decline of serum T with ageing to subnormal levels has important consequences for the health of elderly men.[4]

In view of the findings that ageing in itself is not a key factor in the decline of T levels in some ageing men, the term LOH may be abandoned.[5] Below-normal levels of serum T appeared to be associated with significantly higher risks of all-cause and cardiovascular mortality.[6] In further analysis, the level of serum T and the presence of sexual symptoms were significant and independent factors.[7] In a recent review, advanced age, obesity, a diagnosis of metabolic syndrome and a poor general health status were the predictors of LOH and its co-morbidities.[8] Diabetes mellitus was correlated with hypogonadism in most studies, but could not be proven to be a risk factor.[2] In statistical analysis, diseases such as coronary heart disease, hypertension, stroke and peripheral arterial disease were not predictive of hypogonadism, but they could be shown to correlate with incident low T. There is now substantial evidence that low levels of T are associated with significant long-term negative health consequences.[8] In the ongoing European Male Ageing Study (EMAS), it was found that more than 50% of subjects with LOH had one or more common morbidities. Most prevalent were hypertension (29%), obesity (24%) and heart diseases (16%).[9] In a follow-up of the same study, obesity, weight gain and increased waist circumference were identified as the predictors of incident hypogonadism.[10] Remarkably, in the EMAS sexual symptoms are powerful indicators of LOH. This was demonstrated in one study that established an inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level. The authors attributed great value to these sexual symptoms and concluded that LOH can be defined by the presence of at least three sexual symptoms when also total testosterone levels are <11 nmol/l (3·2 ng/ml) and free testosterone levels are <220 pmol/l (64 pg/ml).[11]

Upon normalization of serum T levels following administration of T, a number of beneficial effects particularly on weight, fat distribution and metabolic factors have been observed.[12,13] While treatment of obesity is commonly a frustrating experience for patient and doctor, several studies indicate now that normalizing serum T levels may produce substantial and sustained effects on weight reduction, associated with a number of benefits on lipids and glycaemic control.[14–17]

This study reports the effects of long-term testosterone replacement treatment (TRT) in a cohort of elderly men. In a subgroup of these men, there was an intermission of T treatment because costs of the T preparation were no longer reimbursed and in a small group because of an incidental prostate carcinoma. In all of these men, T treatment could be reinstated. So, we present a comparison of data for a group of men who were continuously treated with T treatment and a group who had a temporary intermission of T treatment but eventually resumed treatment.