Replacement with sex steroids in hypopituitary men and women: implications for gender differences in morbidities and mortality.

Women with hypopituitarism experience significantly elevated prevalence of cardiovascular risk factors, myocardial infarction, stroke, and mortality compared to the general population, while men approach general population rates.

• There are marked sex disparities in the morbidity and mortality experienced by patients with hypopituitarism
• In women with hypopituitarism, the prevalence of many cardiovascular risk factors, myocardial infarction, stroke and mortality are significantly elevated compared to the general population
• In men with hypopituitarism, cardiovascular risk factors and mortality approach that of the general population
• The reasons for the sex disparities in mortality remain poorly understood

Untreated gonadotropin deficiency is independently associated with an increased mortality risk when women and men are considered together.

• When women and men are considered together, untreated gonadotropin deficiency is independently associated with an increased mortality risk
• Gonadotropin deficiency is caused by a deficiency of either hypothalamic GnRH or pituitary gonadotropins (FSH and LH)
• HPG axis dysfunction results in oestrogen and testosterone deficiency in women and men, respectively

Treatment with sex hormone replacement reduces mortality risk in patients with gonadotropin deficiency to levels comparable to those with an intact gonadal axis.

• Treatment with sex hormone replacement reduces the mortality risk comparable to those with an intact gonadal axis
• Replacement of deficient sex hormones is the mainstay of treatment in individuals not seeking fertility
• Oestrogen and testosterone replacement in women and men, respectively, have numerous beneficial health impacts

Oestrogen and testosterone replacement provide multiple beneficial health effects including improvements in body composition, insulin sensitivity, lipid profiles, and bone mineral density.

• Benefits include improved body composition, enhanced insulin sensitivity, improved atherogenic lipid profiles and increased bone mineral density
• Oestrogen replacement in women also reduces the risk of developing type 2 diabetes mellitus
• These benefits apply to oestrogen replacement in women and testosterone replacement in men

The hypothalamic-pituitary-gonadal axis is described as the most sexually dimorphic pituitary hormone axis.

• The HPG axis is characterized as 'the most sexually dimorphic pituitary hormone axis'
• HPG axis dysfunction results in oestrogen deficiency in women and testosterone deficiency in men
• Hypopituitarism is a heterogeneous disorder characterised by a deficiency in one or more anterior pituitary hormones

Several potential explanations for sex disparities in mortality in hypopituitarism have been proposed.

• Potential explanations include the reversal of women's natural survival advantage over men
• Premature loss of oestrogen's cardioprotective effect is identified as a potential explanation
• Less aggressive cardiovascular risk factor modification is cited as a contributing factor
• Inadequate oestrogen replacement in women with gonadotropin deficiency is also identified as a potential explanation

Historical inertia and unfounded safety concerns about oestrogen replacement have impeded treatment of gonadotropin deficiency in women of reproductive age.

• Historical inertia and unfounded concerns about the safety of oestrogen replacement in women of reproductive age have impeded the treatment of gonadotropin deficiency
• These concerns are described as 'unfounded' in the context of women of reproductive age
• This is identified as a factor potentially contributing to inadequate treatment and worse outcomes in women