MedUni Vienna: Patients with adrenogenital syndrome more likely to suffer from sexual dysfunction

If a form of AGS is present, conversion of cholesterol into the hormones cortisol and aldosterone is inhibited

Intersex people cannot be clearly assigned to one gender, since their chromosomes, hormones, gonads and external sexual characteristics can have both male and female elements. A variant of this clinical picture known medically as "disorders of sex development" is adrenogenital syndrome (AGS), a congenital disorder affecting steroid hormone production in the adrenal cortex. Doctor of internal and sexual medicine Michaela Bayerle-Eder and biochemist Sabina Baumgartner-Parzer from MedUni Vienna's Department of Medicine III are studying the sexual function and sexual orientation of a group of women with severe and mild forms of AGS. An important initial finding is that they are much more likely to suffer with sexual dysfunction and problems with gender identification than healthy women. This topic is also to be discussed at the 5th Scientific Symposium of the Austrian Society for Sexual Medicine and Sexual Health, to be held in Vienna General Hospital on 23 and 24 November 2018.

Adrenogenital syndrome (AGS) is the name for a group of genetic disorders with autosomal recessive inheritance, in which production of certain endogenous steroid hormones in the adrenal cortex is disrupted. In AGS, inherent genetic modifications cause a reduction in the production of cortisol and aldosterone and, at the same time, an increase in the production of male hormones. The term AGS covers several diseases, which are named according to the genetically modified enzyme involved, by far the commonest form being 21-hydroxylase deficiency. Both boys and girls can suffer from AGS but each gender manifests different gender-specific symptoms.

If a form of AGS is present, conversion of cholesterol into the hormones cortisol and aldosterone is inhibited. These hormones are therefore no longer produced in sufficient quantity. Since the body attempts to offset this deficiency by producing more hormones, the adrenal cortex is overstimulated.   However, since this is impossible due to the enzyme defect (e.g. 21-hydroxylase), the body produces a surplus of hormone precursors and these are then converted into androgens (i.e. male hormones) in other metabolic processes. AGS is therefore characterised by a deficiency of cortisol and aldosterone and a surplus of male hormones.

The clinically severe form is known as "classical AGS". This form of the disease can produce life-threatening symptoms right from birth, which could bring about a salt wasting crisis in both genders or masculinisation of the external sexual characteristics in girls. The latter range from enlargement of the clitoris right through to formation of a pseudo-penis, despite the presence of internal female genitalia.  Both genders experience rapid growth during childhood causing false precocious puberty with development of pubic hair and breaking of the voice. A rapidly growing penis in boys and the absence of periods in girls are then further signs of "classical AGS", as is excessive body hair and acne. A new-born screening programme also conducted in Austria includes checking for AGS, to prevent life-threatening salt wasting crises and initiate substitution therapy as soon as possible.

A milder form is "non-classical AGS", where symptoms do not occur until later in life, often not being diagnosed until after puberty. These patients have a "milder genetic defect" in the corresponding enzyme, so that the adrenal cortex can still produce a certain amount of cortisol and aldosterone.

Before puberty, affected children are often taller than their contemporaries but, without treatment, they will be small as adults. "Non-classical AGS" can even be so minimal that, although there is a biochemical disruption in the hormone balance, no marked clinical symptoms are exhibited, so that often AGS is only diagnosed when sufferers fail to conceive children.

Doctor of sexual and internal medicine Michaela Bayerle-Eder and biochemist Sabina Baumgartner-Parzer from the Division of Endocrinology & Metabolism of the Department of Medicine III are looking at the extent to which prenatal androgenisation due to AGS can potentially influence the sexual identity of female patients. The aim of this Europe-wide research project is to clarify to what extent AGS patients with severe and mild forms also suffer from sexual dysfunction and what differences exist in their gender roles and sexual preferences.

Based on their sexual history and various specific parameters, it was found that AGS patients suffer more from sexual dysfunction and sexual stress than women from the general population. No significant differences were found between the group with classical and the group with non-classical AGS. There is an overall tendency to greater restriction of sexual function and greater psychological stress in patients with non-classical AGS and patients with classical AGS are more likely to be orgasmic. A large proportion of all volunteers state their gender role as mannish/masculine. As regards sexual orientation, women with classical AGS displayed a greater homosexual preference. Prenatal hyperandrogenaemia therefore seems to influence gender role and sexual preference."

In summary, it seems that patients with non-classical AGS, with less obvious symptoms and mild genetic defects, suffer more due to the late diagnosis, since they have had longer without any explanation of their "otherness" and have not received any treatment. Says Bayerle-Eder, who is also President of the Austrian Society for Sexual Medicine and Sexual Health: "For women with signs of masculinisation (such as acne and increased body hair), menstrual problems, the inability to conceive and sexual dysfunction, it is therefore important to also consider non-classical AGS when making a diagnosis and to order genetic tests where appropriate.

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5th Scientific Symposium of the Austrian Society for Sexual Medicine and Sexual Health. 23 – 24 November in Vienna General Hospital, MedUni Vienna. The keynote lecture will be given by the philosopher Konrad Paul Liessmann.
For information: www.sexualmedizin.or.at