Low levels of anti-Müllerian hormone (AMH) are associated with poor sperm quality among infertile men. Conversely, higher levels of AMH may indicate which infertile men could benefit from treatment with an anti-osteoporosis drug, which may temporarily improve sperm quality and thereby increase the probability of achieving pregnancy.
AMH is normally associated with biological sex development in the male fetus or the hormonal transition in connection with puberty in boys. Now a new study shows that AMH also affects infertile men.
The researchers behind the study investigated whether the levels of AMH are associated with sperm quality among infertile men, and they are. According to a researcher, this indicates that assessing AMH may need to be included in the andrological examination of male infertility.
This perspective is interesting, since there have been indications that treatment with denosumab, an anti-osteoporosis drug, can improve sperm quality among infertile men with moderate-to-high levels of AMH.
“It appears that we can activate a reserve capacity for sperm production among infertile men by giving denosumab to the men with moderate-to-high levels of AMH. We are conducting large studies on this, and if this is confirmed, these infertile men could be treated with a drug that could give them a window of higher semen quality, which will increase their chances of achieving pregnancy,” explains Rune Holt, MD and PhD fellow, Department of Growth and Reproduction, Rigshospitalet, Copenhagen.
AMH: here, there and everywhere
AMH plays different roles throughout life.
As a male fetus develops, AMH helps to regulate regression of the female genitalia (the Müllerian ducts), and male fetuses that cannot produce AMH are born with ovaries, a uterus and the upper part of the vagina.
Boys also have enormously high levels of AMH before puberty, but this drops during puberty from approximately 1,000 pmol/L to just 50 pmol/L.
Among women, AMH can indicate how many eggs they have left in their ovaries and is also called “the ovarian reserve hormone”. A twist to the story is that women with polycystic ovary syndrome have very high levels of AMH.
“AMH is thoroughly studied among women, but among men it has never been particularly interesting, because the levels of AMH probably do not have much effect on fertile men. However, in this study we focused specifically on how the levels of AMH are associated with testicular function among infertile men,” says Rune Holt.
The researchers examined the levels of AMH in the blood of 307 infertile men and divided them into three groups according to these levels. The researchers then compared the AMH levels with testicular function as measured by various reproductive hormones in the blood and by semen quality.
AMH is produced in the Sertoli cells, which support the germ cells during spermatogenesis and are crucial for sperm production.
The research has been published in BMC Medicine.
Noticeably better sperm quality among infertile men with high AMH levels
The results indicate that the levels of AMH are clearly associated with both semen quality and the function of the Sertoli cells.
Men with the lowest levels of AMH clearly had the worst testicular function and Sertoli cell function and the poorest semen quality. Specifically, the third of infertile men with the highest levels of AMH had 200% higher sperm production.
Similarly, the production of the hormone inhibin B, which is also produced by the Sertoli cells during sperm formation, was 59% higher among infertile men with high levels of AMH versus infertile men with low levels of AMH.
Conversely, the levels of follicle-stimulating hormone (FSH), which is also associated with the function of the Sertoli cells and spermatogenesis, were 38% lower among infertile men with high levels of AMH. Lower levels of FSH are associated with better semen quality.
Finally, the researchers also examined testicle size as an indication of sperm production and found a slight difference, since infertile men with high levels of AMH in the blood had slightly larger testicles than men with low levels of AMH.
“There have been other small studies in this field, but there has been a lack of focus on infertile men with low levels of AMH. We can show that low AMH is a poor prognostic sign for infertile men, but not necessarily for men with normal semen quality,” explains Rune Holt.
May help to understand infertility
Rune Holt says that understanding the significance of AMH as a marker for poor semen quality among infertile men can be useful in several ways.
The results indicate that something happens during puberty among some men, with the levels of AMH declining dramatically from high to almost zero. This could be the maturation of the Sertoli cells, which happens during puberty.
“We interpret the data such that the levels of AMH can indicate poorer testicular function but also that an infertile man has more Sertoli cells that do not contribute to producing sperm. Perhaps these Sertoli cells can be considered as a reserve capacity that can potentially be activated and boost semen quality, so that the chance of achieving pregnancy increases,” says Rune Holt, adding that “the results also indicate that you can probably determine whether an infertile man has reduced semen quality by the end of puberty. This requires determining the level of AMH and comparing it with semen quality.”
Treatment with denosumab increases sperm production
Rune Holt says that the results may also pave the way for improving treatment for some infertile men based on measuring their AMH levels.
Some research results have indicated that treating infertile men with moderate to high levels of AMH with denosumab, which is usually used as anti-osteoporosis therapy, can stimulate the formation of sperm. This gives infertile men a few months of improved semen quality, during which they have better chances of achieving pregnancy.
The researchers are carrying out a few more studies of this kind to investigate the clinical potential.
“If the levels of AMH are high, this may indicate that there is a greater reserve capacity of Sertoli cells, which we can activate with denosumab. Conversely, we may have to be careful about giving men with low levels of AMH denosumab, since this probably will not benefit them,” concludes Rune Holt.