A recent review article in the journal Blood looked at the issues around reproduction and sex in sickle cell. Unfortunately, there is little hard fact and lots of anecdote and speculation in this area, but the author, Dr Kim Smith-Whitley, from The Children’s Hospital in Philadelphia, attempts to summarise what is known and what areas need further research. This blog will concentrate on the issues for men and a following one will address those for women.
Delayed puberty. In boys with sickle cell, sexual maturation and the teenage growth spurt, are usually delayed for 1-2 years, compared with boys of the same age who don’t have sickle cell. This is normal and expected, although can sometimes can cause a lot of distress, with boys feeling that they are being left behind by their friends and contemporaries. However, with patience the vast majority eventually pass through puberty and develop normally thereafter without any need for medical intervention.
Plotting a patient’s weight and height on a growth chart every time they come to clinic, is sometimes a useful way to track the changes, reassure the patient and their doctor and pick up early on if there is any major delay. Maintaining a good calorie intake is essential for normal growth but is sometimes very difficult in the presence of frequent painful crises and hospital admissions. Referral to a dietician can sometimes be helpful and all patients should be given dietary advice and supplements if necessary Fitness exercise and weight training, as well as improving general health, may also be helpful psychologically, provided the exercise is undertaken carefully and within the limits imposed by the sickle cell.
Apart from delayed puberty the other main reproductive complications encountered among men with sickle cell are priapism, hypogonadism and sperm abnormalities.
Priapism is probably the most familiar. It refers to the occurrence of painful erections of the penis, not related to sexual excitement, which can occur at any age and at any time of the day or night, although most commonly they wake patients from sleep. Usually they go away on their own after 10-20 minutes (known as minor or stuttering priapism), but sometimes can last for hours at a time and can be excruciatingly painful (known as a major priapism). Minor attacks can be irritating and embarrassing and can lead to sleepless nights and exhaustion. Of more concern though, minor attacks occurring on a frequent basis, or a single major attack lasting for more than an hour, can lead to permanent damage to the penis. This is the most serious result of priapism and, as a result of the scar tissue laid down in the penis, the man can be left impotent, unable to have an erection at all, or only able to achieve partial or short lasting erections. Medically this is called erectile dysfunction.
Helping men with erectile dysfunction is difficult and the treatments available are not very effective. it is much better to prevent it happening in the first place. This is now possible with drug treatment; etilefrene hydrochloride, also known as Efortil, can prevent recurrent attacks of priapism and the risk of erectile dysfunction, but does not interfere with normal sexual activity. What can you do as a patient? Well the first thing is to report all episodes of priapism to your doctor, even if the attacks only occur occasionally and are short lasting. Sometimes simple interventions, such as passing urine, taking a warm bath or avoiding prolonged sexual arousal can help to prevent or resolve the attacks, but if they persist despite this your doctor can prescribe medication, such as etilefrene.
If you are unlucky enough to have a major attack, one lasting more than an hour or one which is extremely painful, it is very important to go to your Accident and Emergency Department straight away. Do not delay seeking help hoping it will go away on it’s own – it won’t. Emergency treatments are available which, if implemented quickly enough, will resolve the attack, relieve the pain and prevent the development of erectile dysfunction. The usual treatment involves removing some of the sickled blood from inside the penis using a needle or cannula and then injecting etilefrine, or a similar drug, into the penis. The drug relaxes the blood vessels and allows the blood to begin to flow normally again and as it does so the priapism goes down. The longer treatment is delayed the less likely it is to work. Failure of simple interventions means that it then becomes necessary to consider an exchange blood transfusion and surgery. Yet another reason not to delay, but to present to the Emergency Department as soon as you suspect that you have a major attack.
Hypogonadism is a less well known problem. The word hypogonadism means a failure of the gonads, or testes, to work normally. It is not known how many men with sickle cell are affected by this complication, but some estimates put the number as high as 25%. The main symptoms are a low sex drive or libido, poor quality erections, infertility or inability to conceive a baby, thin or sparse facial, armpit or pubic hair and small sized testes. Your doctor can confirm the diagnosis by measuring the level of testosterone in your blood. Testosterone is the male hormone normally produced by the testes and the level in the blood will be low if the testes are not working properly.
No one is quite sure why this problem sometimes develops in men with sickle cell. It may be due to a sickle cell crisis affecting the testes, interfering with the blood supply and damaging the function of the organs or it may possibly be due to a deficiency of the element zinc. In men who have iron overload, due to repeated blood transfusions, the excess iron may be deposited in the pituitary gland, preventing the normal function of that gland, one of those functions is to stimulate the testes to produce testosterone. Finally, long term use of powerful pain killing drugs, including many opiate drugs such as morphine and diamorphine, can suppress testosterone production and result in hypogonadism. This mechanism may be particularly relevant in many men with sickle cell who use these drugs to manage the pain of recurrent sickle cell crises.
Treatment of hypogonadsim is controversial, but extra testosterone, given by injection or skin patches, can have a dramatic effect in reversing the symptoms and signs of testosterone deficiency. Long term supplementation with testosterone is however associated with a variety of serious health complications. The frequency, causes and treatment of hypogonadism in men with sickle cell disease is an area which needs a lot more research.
Abnormalities in the sperm. These are very common in men with sickle cell. They include a reduction in the number of sperm, a reduction in their motility, or how effectively they swim and the presence of more abnormal looking sperm. It is not at all clear what causes these abnormalities, and it is not even clear whether these changes have any effect on fertility or not. Sperm abnormalities can also be induced by the treatments that some patients receive, particularly bone marrow transplantation (BMT) and hydroxycarbamide, and here there is also considerable confusion.
BMT may sometimes, but not always, result in complete loss of sperm production and consequent permanent infertility. It is now customary to offer men who are about to undergo BMT “fertility preservation options”. These include depositing some of your sperm in a frozen sperm bank, a technique known as cryopreservation. The sperm can then be unfrozen at a later date and your partners’ eggs fertilised in a test tube before being re-implanted for the embryos to grow in the mother’s womb. For young boys having a BMT, who have not yet gone through puberty and who are not yet producing any sperm, it may be possible in the future to remove some tissue from the testes and store this frozen for future use, although at the moment this remains an experimental technique only.
Hydroxycarbamide is another treatment which theoretically could affect the ability of men who are taking the drug to produce sperm. Unfortunately, there is no good evidence to prove this one way or another. The situation is made still more confusing because, as noted above, abnormalities in sperm are commonly seen in sickle cell men even when they are not taking hydroxycarbamide. If the drug does affect sperm production, there is no good data showing that this reduces fertility, or showing the time course of recovery after the drug is stopped. This is clearly another area in which new research is needed urgently. In the meantime, most doctors would consider that the very significant proven benefits from taking hydroxycarbamide, including reduced crises and attacks of the acute chest syndrome and improved mortality, outweigh any possible theoretical damage to sperm production.
Reproductive issues in sickle cell disease. K Smith-Whitley. Blood (2014), volume 124 (number 24), pages 3538-3543