Preoperative hormone evaluation in hypospadias
Hypospadias is a congenital malformation in which the urethral opening lies on the underside of the penis instead of its tip. While severity of hypospadias is classified according to the urethral opening, hypospadias is sometimes associated with small penile size. Let’s delve into the facts about hypospadias, its effect on penile size and treatment options.
Understanding Hypospadias:
During development of penis between 8-12 weeks of pregnancy, the urethra (urinary pipe) starts forming from the base of the scrotum to penis, finally proceeding forwards towards the tip. Hypospadias occurs when the tissue forming the urethra doesn’t fully close during fetal development. This results in the urethral opening appearing anywhere on the underside of the penis, from the glans (mildest form) to the scrotum (severest form).
Hypospadias and Penile Size:
The relationship between isolated hypospadias and penile size is complex.
In most cases of distal or minor hypospadias, usually the penis size is normal and is comparable to unaffected boys. Less than 10% of boys with distal hypospadias may have a smaller penis. In severe varieties such a s proximal penile, penoscrotal, scrotal or perineal hypospadias, penis may be small in almost 50% of the cases.
To understand the correlation of hypospadias and small penis, lets first understand how hormones work to cause penis growth:
Penis formation is complete by 12 weeks of pregnancy. During the rest of the pregnancy, under the influence of hCG hormone, which is released from placenta of the mother, the testes of developing baby produce a hormone called testosterone. Testosterone is the main male hormone, which is responsible for male pattern of facial hair growth, beard formation, muscle development, thickening of voice etc. which are male external features at puberty. However, testosterone is the not main hormone responsible for penis growth. Testosterone gets converted into dihydrotestosterone (DHT) which is much stronger variant of testosterone and is the main hormone responsible for penis size increase. Collectively, testosterone and dihydrotestosterone are called androgen hormones. Both testosterone and dihydrotestosterone act via androgen hormone receptors. For a moment think of a lock and key mechanism. Hormones are the keys which go and bind to receptors which are the locks. Working together, the lock and key, unlock the penis development. So, inadequate androgen action either due to:
A) Less production of testosterone
B) Testosterone not getting converted to dihydrotestosterone
C) or androgen receptors are not working,
Then the penis size will remain small.
Hormonal Reasons which may cause short penis length in hypospadias:
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- Hormonal disorders: Some children with hypospadias may have hormonal issues like testosterone production defect, androgen insensitivity or 5 alpha reductase deficiency. Whenever we find penis size to be very small along with hypospadias, we typically do a detailed hormonal evaluation to find out the real cause and then treat it.
- Low birth weight or premature babies: Our experience shows that babies which are born ahead of their full-term date of birth usually have a smaller penis. This happens as the main penile growth in a baby in pregnancy happens in the last few weeks. If the baby does not receive hCG in the last weeks of pregnancy, then testosterone and DHT is also low, leading to smaller size of penis. Same thing happens in babies who have IUGR or low birth weight, their body produces smaller quantities of hormones for penile growth in the last few weeks of pregnancy.
Addressing small size of penis with hypospadias:
First, penile size should be measured properly in all children with hypospadias. Two measurements are important – penile length (stretched penile length) and glans diameter. Normally in a 6-month-old child, the SPL should be atleast 35mm and glans diameter should be atleast 14 mm.
If the child was born preterm or was low birth weight, and the glans diameter is atleast 11-12 mm, then as a first choice we give testosterone injections. These injections are given 1 month apart in 2 doses. Typically, it takes 3 months for the penis size to become normal. And then we plan the hypospadias repair surgery. Testosterone injection response also tells us how the penis will respond to natural testosterone at time of puberty and is a good marker to assure the parents and the doctor.
If the penile size is very small in a full-term baby or the baby has severe hypospadias, then we do a full hormonal test in the form of hCG stimulation test.
hCG stimulation test:
Day 1: Blood sample is collected to measure levels of Serum LH (Luteinizing hormone), Serum FSH (Follicle stimulating hormone), Serum AMH (Anti mullerian hormone) and Serum testosterone levels. Following this first injection of hCG with dose of 3000IU/m2 BSA is administered in intramuscular route
Day 2: Second injection of Inj hCG 3000IU/m2 BSA administered via intramuscular route
Day 3: Third injection of Inj hCG 3000IU/m2 BSA administered via intramuscular route
Day 4: Blood sample is collected to measure Serum testosterone and Serum 5-alpha DHT (dihydrotestosterone) levels.
Through this test we are assessing the pre and post injection rise in testosterone levels. hCG stimulates the testis to produce testosterone which in turn is converted to DHT (dihydrotestosterone). Also, the conversion of testosterone to DHT is assessed.
Based on the hCG stimulation test results, there are three possibilities at this stage:
- Testosterone does not rise: That means there is testosterone biosynthetic defect. This can be solved by giving external testosterone injections.
- Testosterone rises normally but DHT does not rise as evidenced by T/DHT ratio: This is suggestive of 5 alpha reductase enzyme defects. Such children will require DHT gel to help them achieve normal penile size.
- Both Testosterone and DHT rise normally: There is a possibility of androgen insensitivity in such cases. We give testosterone injections, but they may not work in all the cases.
All these tests and their interpretation should be done by an experienced pediatric urologist or a hypospadias surgeon or a pediatric endocrinologist.
DHT (Andractim) gel:
Dihydrotestosterone is a more potent form of testosterone and is responsible for the direct growth of the penis. It is mainly used in children and adults with DHT deficiency or 5 alpha reductase biosynthetic defect.
It is available as a 2.5% gel in the name of Andractim. This gel is for external use over the penis only. Since this gel is not manufactured in India and is imported by licensed dealers it is expensive compared to testosterone.
The gel is applied all over the penis once daily for 3-6 months. When we recommend this gel to a child its better if the father applies it since it’s a male hormone. If the mother will be applying it to the child, then she should wear gloves.
The side effects of this are hyperpigmentation of the skin over the penis and local hair growth. These are temporary and will normalize once the gel application is stopped.
At Hypospadias foundation India, we have been taking care of children and adults with hypospadias for last 16 years with best-in-class results. Children with hypospadias and small penis should be well evaluated whenever needed by a hypospadias expert surgeon. This evaluation is important in childhood itself to lay a future healthy path for the child. There is detailed measurement and counselling done before any hypospadias surgery at our centre. Dr A.K.Singal is currently rated as the best hypospadias surgeon expert in India for such cases. Dr Singal works along with Dr Ashwitha Shenoy in MITR Hospital Navi Mumbai to help children and adults get good results for treatment of hypospadias.