September 16th 2025
In this event report, Malcolm Rochefort summarises the intriguing talk by Dr Ian Jefferson, a retired paediatric endocrinologist
Dr Jefferson talk was enticingly entitled ‘Sugar & Spice or Slugs & Snails?’
We’re familiar with the rhyme suggesting that boys and girls are made from different things – pleasant (girls) or unpleasant (boys)! In fact, apart from the obvious external signs of sex, what are the genetic determinators and what do they really affect in terms of sexual development in human beings?
We learnt from Dr Jefferson that sexual development has, genetically, a very complicated pathway and subtle variations in chromosomal inheritance can produce some remarkable changes in the developing baby, child and adult human being.
Ian had an eminent career in paediatric endocrinology, based originally in Hull, then several years in the Middle East (Dubai and Abu Dhabi), that enabled him to develop a wide knowledge about the mechanisms of sex differentiation, how to manage clinical problems and ethical decision making. The relatively closed (historically) societies of the Emirates do tend to lead to unusually high rates of certain genetic abnormalities which, while unfortunate for the population, can be used to enhance medical general understanding of the causes and effects.
Most people are familiar with the fact that we humans have 23 chromosomes, and that one of these has a major influence on sexual determination. The chromosomes themselves are composed of two very long strands of DNA (deoxy-ribose nucleic acid). The ‘sex’ chromosome is in most humans XX or XY. XX results in females and XY in males. However, most of us also know that there can be abnormalities. Apart from the obvious potential abnormality of an extra chromosome (XXY, for example), or lacking one (45X – Turner’s syndrome), the differences can be much more subtly caused.
Research and knowledge around the causes for anomalous sexual development in the last few decades means our understanding is far better than in the past.
The basic human phenotype or blueprint is female – hormones leading to the production of certain enzymes, for example, during the development of a foetus, lead to certain aspects of development including formation of a penis, testes and ovaries. Later, excess or lack of hormones can lead to hair and breast formation in young adults. Perhaps less well known is that these chemicals can also influence development of the brain in subtle ways – for example that make young girls more naturally attracted to dolls and social games, and boys more inclined towards inanimate objects such as guns and toy cars, etc. Yes, there are cultural influences on any behavioural traits, but some of these inclinations even begin during brain development in the womb.
Ian Jefferson illustrated his talk with some concrete examples in the news or from his experience. One example was Caster Semanya – the South African athlete who grew up as a girl and was in physical appearance a female (i.e. no penis or testes) but excelled at sports requiring muscle strength, winning against female opponents, with 5 gold medals won between 2009 and 2017. On analysis, she was found to be XY – normally this would be genetically male. However, as a foetus, she developed with alpha-reductase deficiency. This affects the foetal development pathway which results in no uterus, or testes descending, but internally the gonads (sex glands & organs) are testes. Unfortunately, apart from the problems of classification in sport, she also suffers as she matures because testosterone is still produced leading to obvious male characteristics developing (hair distribution, as well as muscle strength). Now undergoing treatment with testosterone suppression, she identifies as a ‘different kind of woman’. She was brought up as a girl in a large family having several brothers and sisters, so quite understandably, psychologically, still feels herself to be a woman.
Another illustrative case was of a 7-year-old girl presenting with an inguinal hernia. On testing, the hernia was found to be a testis and chromosome analysis showed she was genetically male (46XY), but with an X-linked recessive genetic inheritance resulting in complete androgen insensitivity. Internally she had testes, no uterus and a shortened vagina. The condition is known as Complete Androgen Insensitivity Syndrome (CAIS). Androgen is a hormone with critical influence on foetal sexual development. Excess androgen in genetically female foetuses (46XX) will result in ‘virilised’ female – physically appearing as a male. Conversely, insufficient androgen in a genetically male foetus (46XY) will result in an incompletely virilised male – physically appearing as a female. In this case the recommended management would be removal of the testes. She can then live and develop as a female, but would be infertile.
The final case was rather sad – an apparent male born in the UAE who became ill at 4 weeks of age. Analysis showed he was genetically female (46XX), but had developed with a critical enzyme deficiency (21- hydroxylase). This enzyme is needed to convert progesterone into aldosterone and cortisol, which in this case can’t occur, and instead the excess is converted into androstenedione and testosterone – which results in excessive virilisation. Physically the baby looked male, with a penis. The condition is called Congenital Adrenal Hyperplasia (CAH). Other side effects are salt wasting (lack of sodium), and glucocorticoid deficiency, i.e. ultimately fatal. These deficiencies can be treated successfully, enabling the child to survive. Unfortunately, the recommended case management would then be surgery to allow development at puberty as a girl. However, culturally the father would not accept or allow this to happen. This will almost certainly result in problems during puberty.
Most of these conditions are very rare across the world, one in several thousands (under 0.1%). However, cultural and historical development of populations can result in some conditions being over-represented in some populations, especially where interfamilial marriage is more common (e.g. between first cousins). Some Polynesian societies have such a high frequency of anomalous sexual development that this is freely recognised as a third sex.
Differences of Sexual Development (DSD) must always be treated carefully. Golden rules for physicians when there is any doubt about the sex of a baby or child are: don’t guess; get senior expert opinion; test for chromosome situation and abnormalities as soon as possible. There will be serious implications if not treated, from life-threatening to psychological and societal development and acceptance.
I think we were all blown away by the complexities of normal and abnormal sexual development that most lay people are unaware of. Clearly, there are more possibilities that those discussed here, but we all understood that this is a very complex topic that requires considerable expertise and human understanding and tact in tackling – for the child, parents and society as a whole.