I have Kallmann syndrome, which is a rare hormone condition that affects puberty and fertility. It means I have to be on life long hormone replacement therapy.

I had a late diagnosis and treatment which meant I did not have what I would regard as normal teenage years and adolescence.

I have never been formally tested form any form of autisim but others with my condition have. I certainly have developed personality traits over the years, especially linked to social situations. I have never been sure whether this has been linked to hormone levels and not feeling like a "normal" adult or if there was something else going on.

As an example this week at work we had a social gathering one lunch time at work to celebrate somebody's birthday.

I just could not bring myself to attend, to be able to sit around colleagues and have casual conversations or small talk

Everybody is friendly, I just physically could not feel comfortable being in a social group and being relaxed. I needed to go and eat lunch on my own. I have been like this for a while, needing to socially recharge at times.

The more I read about autism spectrum disorder the more I think I fit into it, even though I have never been formally tested.

There may be a link to Kallmann syndrome, my poor hearing certainly does not help my social awareness. It can not solely been down to having KS. I know KS friends who are very friendly and social. I certainly can not blame my behaviour on having KS but the late diagnosis and treatment probably did not help.

>Autistic individuals have a higher rate of social anxiety than the general public. For many, the anxiety is not an irrational fear. As discussed by users on Reddit, there is a consensus that autistic anxiety is often a logical response to real-world obstacles like sensory burnout, past social rejections, and the daily fatigue of navigating a neurotypical world.

My hearing aid broke today. So I am going to have to spend a few days in my own quiet little world. Not totally deaf but enough to make it awkward at work, especially for colleagues who have to shout at me.

I sometimes think that my poor hearing and lack of sense of smell have affected my life far more than the more obvious aspects of having Kallmann syndrome. There must be so much I have missed out on just by not hearing conversations or by people thinking I am ignoring them.

If you have Kallmann syndrome and were just told that you have azoospermia, I want to start with something important: this diagnosis is not the same thing as being told your testicles have permanently failed. In fact, Kallmann syndrome represents one of the more treatable causes of severe male infertility. Men with this condition frequently have extremely low testosterone, very small testicles and absolutely no sperm in the ejaculate before treatment. That sounds terrible when you first see the numbers. But the fundamental problem is often not that the sperm producing machinery has been destroyed. The problem is that the hormonal signal telling that machinery to develop and operate never arrived normally. With the correct hormonal treatment, sperm production can often be induced, although treatment requires patience and can take many months or longer.

To understand Kallmann syndrome, you first need to understand how the brain controls the testicles. A small region of the brain called the hypothalamus normally releases gonadotropin releasing hormone, commonly called GnRH, in pulses. GnRH travels to the pituitary gland and tells it to release two hormones, LH and FSH. LH stimulates Leydig cells inside the testicle to produce testosterone. FSH acts primarily on Sertoli cells, which support developing sperm. FSH and the very high concentration of testosterone inside the testicle then work together to support spermatogenesis. In Kallmann syndrome, this system is disrupted because the neurons responsible for producing GnRH do not develop or migrate normally during embryonic development. Without adequate GnRH, the pituitary does not appropriately release LH and FSH. Without LH and FSH, the testicles never receive the normal hormonal instructions required for puberty, testicular growth and sperm production.

Kallmann syndrome is a form of congenital hypogonadotropic hypogonadism. The word hypogonadotropic means that the gonadotropins, LH and FSH, are abnormally low or inappropriately normal for the degree of testosterone deficiency. The characteristic feature separating Kallmann syndrome from other forms of congenital hypogonadotropic hypogonadism is an impaired sense of smell. Some men cannot smell at all, called anosmia, while others have a reduced sense of smell, called hyposmia. This connection seems strange until you understand embryology. The neurons responsible for GnRH production and structures involved in smell develop along related embryologic pathways. When that developmental process is disrupted, reproductive hormone signaling and the sense of smell can both be affected.

The genetics are complicated. Numerous genes have now been associated with Kallmann syndrome and congenital hypogonadotropic hypogonadism, and inheritance can be X linked, autosomal dominant, autosomal recessive or more complex. Some men have additional findings such as a history of undescended testes, a small penis from infancy, hearing abnormalities, abnormal tooth development, kidney abnormalities, cleft lip or palate, unusual hand movements or other developmental findings. Other men look completely healthy except that puberty never occurred normally. Genetic testing can be useful for confirming the diagnosis, understanding inheritance and counseling families, but a negative genetic panel does not exclude Kallmann syndrome because we still do not know every gene responsible for the condition.

The diagnosis often begins much earlier than infertility. A teenager may fail to progress through puberty. Facial and body hair may remain sparse, muscle development may be limited, the voice may not deepen normally and the testicles remain very small. Unfortunately, some men are simply told they are late bloomers and do not receive a diagnosis until much later. In an adult man, I become suspicious when I see low testosterone accompanied by low or inappropriately normal LH and FSH, particularly when there is a history of delayed puberty or an absent sense of smell. Evaluation may include repeat morning testosterone, LH, FSH, prolactin and additional pituitary hormones when appropriate. Imaging of the hypothalamus and pituitary may be necessary to exclude acquired causes of secondary hypogonadism, and magnetic resonance imaging may also demonstrate abnormalities of the olfactory structures. Testicular examination is extremely important because testicular volume provides information about previous pubertal development and can help predict response to fertility treatment.

When a man with untreated Kallmann syndrome provides a semen analysis, azoospermia is common. This is where many men understandably panic. They see zero sperm and immediately start reading about nonobstructive azoospermia, microTESE, Sertoli cell only syndrome and testicular failure. But Kallmann syndrome is biologically different. This is central hypogonadism. The testicles have been chronically understimulated because LH and FSH are deficient. The therapeutic goal is therefore to replace the missing hormonal signals and wake up the reproductive system.

There is one major mistake men with Kallmann syndrome need to understand: testosterone treatment and fertility treatment are not the same thing. Testosterone is excellent for producing many of the effects of puberty and treating symptoms of testosterone deficiency. It can improve sexual function, muscle mass, bone health, energy and secondary sexual characteristics. But testosterone alone does not stimulate sperm production. In fact, external testosterone suppresses pituitary LH and FSH. If the goal changes from maintaining normal testosterone to producing sperm, the treatment strategy generally needs to change.

For fertility, we need to reproduce the hormonal signals that normally come from the brain and pituitary. One approach uses hCG, which acts similarly to LH and stimulates Leydig cells to produce testosterone inside the testicle. FSH is then used to stimulate Sertoli cells and support developing sperm. In congenital hypogonadotropic hypogonadism, combined gonadotropin treatment with hCG and FSH is frequently necessary. Another approach is pulsatile GnRH therapy, which attempts to recreate the normal pulses coming from the hypothalamus and allows the pituitary to release its own LH and FSH. Both strategies can induce spermatogenesis.

This treatment is very different from taking a pill for three months and checking another semen analysis. Men with Kallmann syndrome often begin with extremely small prepubertal testes. Those testes need time to grow and develop before substantial sperm production can occur. Semen analyses are generally followed periodically during treatment, often approximately every three months. Some men produce sperm within several months. Others require a year or longer. The process can be painfully slow, but a semen analysis showing zero sperm early during therapy does not necessarily mean treatment has failed.

Several factors influence the likelihood and speed of response. Larger testicular volume before treatment generally predicts a better response. Men who experienced at least partial spontaneous puberty tend to respond more easily than men with completely absent puberty and extremely small testes. A history of bilateral undescended testes is associated with a more difficult fertility prognosis. Severe congenital deficiency is also important because normal testicular development actually begins long before adulthood. There is a hormonal period during infancy called minipuberty during which LH, FSH and testosterone temporarily become active. Men with severe congenital hypogonadotropic hypogonadism may miss this developmental period, which may partly explain why some have very small testes and require prolonged treatment later in life.

Newer treatment strategies have therefore examined whether giving FSH before adding hCG might be beneficial in men with extremely small testes. The idea is to stimulate and expand the Sertoli cell population before exposing the testicle to high concentrations of testosterone. This sequential approach is particularly interesting in men with severe congenital disease and prepubertal testicular volumes. It is not necessary for every patient, and the optimal regimen continues to be studied, but it demonstrates how fertility treatment in Kallmann syndrome is becoming increasingly individualized.

So what are the actual fertility chances? Published literature generally suggests that spermatogenesis can ultimately be induced in a substantial majority of appropriately treated men with congenital hypogonadotropic hypogonadism, although estimates vary considerably depending on disease severity, previous puberty, testicular size, cryptorchidism and treatment protocol. Reviews commonly report sperm appearing in approximately three quarters or more of treated men, while particularly severe Kallmann syndrome can be more difficult. Importantly, the sperm count does not necessarily have to become normal for fatherhood to become possible. A man may produce relatively small numbers of sperm but still have enough for natural conception, intrauterine insemination or IVF with ICSI.

This is an important difference between treating fertility and chasing a normal semen analysis. Our goal is a child, not a perfect laboratory report. Once sperm appear, I frequently think about cryopreservation. If you spent a year stimulating sperm production and finally have sperm in the ejaculate, freezing samples can provide valuable insurance against future fluctuations. Depending on the sperm concentration, motility and the female partner's fertility, couples may continue trying naturally or proceed to assisted reproduction.

Assisted reproduction can be very successful in this population. A systematic review involving men and women with congenital hypogonadotropic hypogonadism undergoing assisted reproduction found 388 pregnancies among 709 patients, with reported fertilization, implantation and live birth outcomes broadly comparable with infertility treatment for other causes. These numbers should not be interpreted as an individual's personal chance of having a child because outcomes depend heavily on both partners, but they reinforce an important point: Kallmann syndrome does not automatically remove biological parenthood from the table.

There is another fascinating aspect of this condition. Although Kallmann syndrome and congenital hypogonadotropic hypogonadism have traditionally been considered lifelong disorders, approximately 10 to 20 percent of patients in some series experience reversal, meaning that reproductive hormonal function can spontaneously recover. Unfortunately, reversal cannot be reliably predicted and relapse can occur, so nobody should stop treatment without medical supervision. Still, it reminds us that this is a disorder of a dynamic hormonal system rather than simply a permanently damaged testicle.

Finally, I do not think we talk enough about the emotional burden of Kallmann syndrome. Many men have felt different since adolescence. They may have experienced delayed puberty, concerns about penis or testicular size, reduced body hair, sexual difficulties or embarrassment changing in locker rooms. Some have spent years wondering why their bodies were different before anyone gave the condition a name. Then adulthood brings another blow when they discover they are azoospermic. It can affect masculinity, relationships, sexuality and confidence in ways that are difficult to explain to someone who has never experienced it.

If you are that man reading this on Reddit after seeing zero sperm on your semen analysis, I want you to understand what the zero means before you assume the worst. In Kallmann syndrome, zero sperm often means the reproductive system has never received the hormonal stimulation required to start the sperm factory properly. It does not automatically mean that the factory is destroyed. Treatment can be long, expensive, frustrating and filled with months where seemingly nothing is happening, but this remains one of the unusual situations in male infertility where we can sometimes treat the underlying hormonal defect and actually induce sperm production.

The important thing is to work with an endocrinologist or reproductive urologist who understands congenital hypogonadotropic hypogonadism. Establish the diagnosis correctly. Understand your genetics when possible. Know your baseline testicular volume. If you want fertility, make sure your treatment is designed for fertility rather than simply replacing testosterone. Give gonadotropin therapy enough time to work. Monitor semen analyses. Freeze sperm when they appear if appropriate. And remember that needing hCG, FSH, GnRH, IUI or IVF does not make the eventual child any less yours.

Kallmann syndrome can delay puberty and it can delay fatherhood. It does not necessarily prevent either one.

References

1. Boehm U, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism: pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology. 2015. PMID: 26194704.
2. Young J, et al. Clinical Management of Congenital Hypogonadotropic Hypogonadism. Endocrine Reviews. 2019. PMID: 30698671.
3. Dwyer AA, et al. Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism. Annals of the New York Academy of Sciences. 2024. PMID: 39190467.
4. Rohayem J, et al. Treatment of congenital hypogonadotropic hypogonadism in male patients. Annals of Pediatric Endocrinology and Metabolism. 2022.
5. Dwyer AA, et al. Fertility induction in hypogonadotropic hypogonadal men. Clinical Endocrinology. 2019. PMID: 30194850.
6. Swee DS, Quinton R. Managing congenital hypogonadotrophic hypogonadism: a contemporary approach directed at optimizing fertility and long term outcomes in males. Therapeutic Advances in Endocrinology and Metabolism. 2019. PMID: 30800268.
7. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility and Male Hypogonadism.
8. Thakker S, Persily J, Najari BB. Kallmann syndrome and central nonobstructive azoospermia. Best Practice and Research Clinical Endocrinology and Metabolism. 2020. PMID: 33419659.
9. Mao JF, et al. Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta analysis. 2018. PMID: 30453944.
10. Bianco SDC, Kaiser UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nature Reviews Endocrinology.
11. Balasubramanian R, Crowley WF. Isolated Gonadotropin Releasing Hormone Deficiency. GeneReviews.
12. European Association of Urology. Sexual and Reproductive Health Guidelines. Management of secondary hypogonadism and fertility.

Did anybody experience disappointment when they first started treatment for Kallmann syndrome / CHH.

I still talk to younger patients who whose doctors never fully explain what changes they would experience when starting treatment or how quickly these changes may occur.

I still think some people expect they will get totally normal puberty & fertility when placed on standard hormone treatment.

I was certainly a little annoyed when first starting treatment that I did not get the full development I was expecting. It was only until I learnt more about the condition I understood why this would be the case but it was certainly annoying at the time.

Being on treatment, male or female, is certainly better than not being on treatment in my view but I quite understand people who do not want to be on treatment. I think it would help if we told more about our condition when we start treatment.

I find it difficult to write about myself but I will give it a go. I am biomedical scientist (blood transfusion) by trade but also enjoy cricket. I like travel and history. I have always been a solo traveller and do enjoy long train rides in different countries and travelling just for the sake of it.

I have a hormone condition, Kallmann syndrome, that has affected my self confidence and I am certainly shy socially but can relax around the right people.

I like animals but have no pets of my own at the moment.

The major part of having Kallmann syndrome that annoys me is missing out on the emotional side of growing up as a teenager / young adult as well as the physical development.

I kind of feel I am not quite a real adult since I missed out on learning the social and life skills I should have done as an adolescent. It seems to be very difficult to catch up once you get left behind.

Even in my 50's, I still get annoyed that I think I missed out on so much as young adult.

I certainly can not blame my life entirely on having KS. Late diagnosis did not help but I certainly made some poor life decisions when I was younger. Even with KS there is so much I could have done differently back then which would have helped me be in a better position today. This is part of the reason why I am so vocal about KS, trying to help people get an earlier diagnosis and not let KS hold them back.

I really do try to be as positive as I can when talking to others about KS. I really do love it when my KS friends get on far better with relationships than I ever did.

I do try to be a positive as I can in discussions with other KS patients around the world. I am always happy to hear and read the positive life stories of people who have coped with this condition far better than I have.

I think part of the reason I like to advocate for this condition is to help people reach an earlier diagnosis and treatment.

I get very frustrated at times that I have never managed to get my relationship life sorted out. Late diagnosis and treatment did not help and I made a few mistakes when I was younger. I can certainly not blame my KS for lack of relationships but it has not helped in gaining experience.

I am now in a situation I do desire physical contact but lack the social skills, experience and energy to engage with people. Lack of social confidence is not an easy thing to overcome. I am more confident about my body image than I used to be. It would have been helpful if I was this confident when I was younger and had more energy and opportunity.

One thing that does annoy me still and I am more than a little perdantic on this point. When first diagnosed a lot of patients are told they will go through puberty.

I do not think it is always fully explained that we do not have a normal puberty and we have to have hormone treatment for life and extra treatment if we want to be fertile for a short while.

Having treatment is better than nothing of course but I do feel sometimes that doctors do not take the time (or want to take the time) to explain about the condition more fully.

Tuesday 14th July. 8:30pm UK time. Seminar presentation on male fertility treatment options.

Seminar on male fertility treatment options for Kallmann syndrome / CHH patients.

A research term based at Imperial NHS Trust in London has undertaken a research project to look at the different types of protocols used for male fertility treatments at various KS specialist centres around the world.

They have collected data from various centres to try to identify the best treatment protocols for patients that give the best outcomes and what type of patients get the best results on treatment.

This will be a short seminar where a couple of the doctors will present the data and explain the results they have found.

They will then be able to answer any specific questions patients may have.

It will only be for about an hour and focus just on the results of their study and to outline potential treatment options.

The meeting will be recorded but if anybody would like to attend the on line meeting via Teams or to submit a question, please let me know and I will send you a link.

My latest testosterone level 14.5 nmol/l, 16 weeks after the last injection. (About 336 ng/dl)

My Hb / red cell count / haematocrit are still too high which is not helping my blood pressure.

Also now in the diabetic range due to high HbA1c.

Was due to have a another Nebido shot but going to wait for a few more weeks.

Have to start Metformin as soon as I can.

Need to loose weight so no more full sugar Coke for me, but I can not cut out chocolate totally. Have to have a little in moderation, I need my comfort food but will have to cut down.

I can not really blame the diabetes and being over weight on having KS.

Routine appointment today. I am fortunate to be seen by one of the most experienced KS specialists in the UK. Today I was seen by one of his junior staff but I still managed to have a quick word with the main guy.

One strange thing about the reproductive endocrinology appointments at the hospital I attend in London is that the clinic is held in a gynaecology / ultrasound out-patient clinic. So I normally end up sitting in the waiting room surrounded by expectant and newly delivered mums.

The appointment focused more on my weight, blood pressure and risk of diabetes than my actual testosterone level. Though they could all be linked in a way. It was a good appointment and no need for any physical exams.

The doctor asked when I last had my Nebido shot and I realised was over 3 months ago. I completely forgot about taking it. It will be interesting to see what my T level is like when the blood test results come back.

I certainly do not feel like I have low T at the moment. More critical will be the HbA1c and lipid results to check for diabetes. I will have to arrange a Nebido injection in the mean time.