Endocrine Abstracts

Hypogonadotrophic hypogonadism (HH) in males is defined both biochemically – low serum testosterone (T) level with LH+FSH levels in or below the lower half of the reference range – and clinically. ie. the person is actually hypogonadal. This clinical criterion is crucial for an accurate diagnosis adult-onset HH in men, because biochemical features are common to other scenarios for which T treatment is presently not indicated. These include afternoon-, or non-fasted- venepuncture, intercurrent or chronic non-gonadal illness of any description, sleep-deprivation, reversed sleep-wake cycles from night shifts, recent abuse of non-prescription opiates or androgens, and hyperinsulinaemic diabetes/prediabetes (where hepatic SHBG secretion is suppressed, leading reduced total T with preserved free T).

A notable feature of the male hypothalamo-pituitary-gonadal (HPG) axis is that, though far less vulnerable to bioenergetic deficit–highly-associated with hypothalamic amenorrhoea in women – it is uniquely vulnerable to obesity. By contrast, obesity per se doesn’t result in women developing HH. Despite interesting preliminary data that should prompt definitive clinical trials of T therapy for men with “diabesity”, there are insufficient safety and outcome data to support off-label prescribing.

For men presenting as adult with this biochemical picture, the diagnosis of HH requiring T therapy may be obvious through absence of secondary sexual characteristics, a history of pituitary surgery, irradiation, or trauma, otherwise unexplained anaemia or osteoporosis, or indefinite high-dose prescribed opiates. By contrast there may be evident signs of systemic illness, such as sleep apnoea, for which therapy should instead be directed at the underlying disease.

However, in the absence of such features, a fasted 8–9 am screen comprising Hb/Hct/ferritin, anterior pituitary function (including calculated free T) and lipid/metabolic profile usually separates men with organic HPG disease (who will likely need MRI pituitary as well as T therapy) from those with physiologically low LH/FSH/T (who require neither, particularly if desiring fertility).