Contrary to prior understanding, many hormones related to spermatogenesis take longer to recover than previously thought, and up to 3 years in some cases after anabolic steroid misuse, according to a fertility expert speaking at the Royal Society of Medicine webinar series.
Dr Channa Jayasena, consultant in reproductive endocrinology and andrology at Imperial College and Hammersmith Hospital, London, gave a talk on male hypogonadism that he admitted might seem provocative to some people but addresses issues that extend current knowledge. The three key issues discussed were: how quickly can men recover fertility after androgen use; how to assist azoospermic men with Klinefelter syndrome (or XXY) father children; and whether testosterone therapy affects progression to diabetes in obese men.
Dr Jayasena spoke at last weeks 3-day webinar held by the Royal Society of Medicine, Endocrinology and Diabetes section, entitled, EDN50:What's new in endocrinology and diabetes 2020?
He began by asking how quicky do men who take anabolic steroids recover fertility? "This has never been studied to much extent."
Self-confessed steroid user and reality television star, Spencer Matthews, said in a tabloid newspaper article that the UK is in the grips of an epidemic of anabolic steroid use, Dr Jayasena remarked. "I see men who take anabolic steroids but then they want a baby and want to know whats next?"
The nearest data to understanding recovery from anabolic steroids comes from studies of the male pill, said the andrologist. This involves giving a high level of progesterone to suppress luteinising hormone and follicle stimulating hormone (in effect the male pill), and then giving the men testosterone replacement. A Lancet paper (Liu at al 2006) involving this regimen looked at the time from stopping the male pill to recovery of sperm. It shows that, by 12 months, all participants had recovered some sperm function, with 80% recovering to the pre-treatment semen level, explained Dr Jayasena. "This has long been presumed to be the measure of recovery. However, this does not resonate with reality and the observation that actually there are many people who dont recover within this time frame and take a lot longer, some with azoospermia[semen containing no sperm]," he pointed out.
Another cross-sectional observational study looked at 41 current users of anabolic steroids, 31 recent ( 3 months since last use), and 21 healthy eugonadal men. All were 18-55 years, exercising at least three times a week. "The critical strength of this study is that these men were all clinically indistinct," Dr Jayasena remarked. "This matching of baseline characteristics is critical for interpretation of the data. Due to recruitment issues, weve never had such a good look at recovery in this way before."
The study looked at the reproductive endocrine profiles including the levels of luteinising hormone, follicle stimulating hormone, and testosterone. In current users, the former two were suppressed and the testosterone level was high, as expected, displaying a hypogonadatropic profile. "Past users and non-users have very similar profiles, suggesting reversible luteinising hormone and follicle stimulating hormone suppression," said Dr Jayasena, adding, "this is really interesting and looking at acne, gynaecomastia, hair loss and smaller testicles all classical features of androgen abuse - appear to persist in many of the men who are past users. Its important we counsel these men that we, the clinicians, are not really clear about how long these side effects will persist."
Results also showed low HDL cholesterol and high triglycerides in users, but not in non-users or past users, and cardiac hypertrophy in users but not past users. "The latter finding is encouraging," Dr Jayasena pointed out.
Regarding fertility, the study by Shankara-Naranya found that when comparing non-users to users of anabolic steroids, it took a mean of 10.7 months for users to recover their luteinising hormone levels to the mean luteinising hormone of a non-user. "But recovery time is highly variable. Luteinising hormone (and testosterone by inference), and sperm concentration seem to recover within a year, with a mean of 10 months, but all the other hormones that are important for spermatogenesis take much longer to recover so follicle stimulating hormone was 20 months, inhibin B was 32 months, sperm motility was 38 months, up to 3 years to recover. This is critical and we didnt know this," reported Dr Jaysena.
"In answer to what is the prognosis for recovery in men after androgen misuse? The endocrine system mostly recovers in the first year but sperm take much longer to recover," he concluded.
Along with Downs syndrome, Klinefelter is the most common chromosomal disorder in men, affecting 1 in 500 men. A total of 90% of those with Klinefelter syndrome are azoospermic, and it has long been assumed to be incompatible with fatherhood.
"Things have changed, and Id like to ask what is the chance of fatherhood for a man with XXY undergoing microdissection testicular sperm extraction (mTESE)?" said Dr Jayasena. "This can be done by dissecting open a testicle and looking for an engorged seminiferous tubule that is likely to be full of sperm," he explained. "If this is confirmed, after some processing, the sperm can be used in intracytoplasmicsperm injection (ICSI)."
It has been known that it was possible for patients with Klinefelter syndrome to father children for the past 20 years, but, asked Dr Jayasena, how successful is it? "Its still an embryonic field," he noted. Referring to a meta-analysis of 37 studies, Dr Jayasena said 40% of men with Klinefelters syndrome had sperm retrieved, and of these 40%, an average of nearly 50% of men had live births after ICSI. But some studies reported 10% and others 90%.
In conclusion, the chances of fatherhood in XXY men undergoing mTESE, is around 20% but a large randomised controlled trial (RCT) is needed to confirm this, said Dr Jayasena.
Finally, the researcher moved on to the third topic of whether testosterone therapy improves the effectiveness of weight loss in men over 50 years with type 2 diabetes. Referring to outcomes of the largest, as yet unpublished, testosterone trial ever, in more than 1000 men by Dr Gary Wittert, from the University of Adelaide, Dr Jayasena described the study.
Most importantly, they did not select men with hypogonadism these results are not valid for hypogonadism because not all men had hypogonadism, explained Dr Jayasena. Two-hour plasma glucose was 7.8 to 15 mmol/l. The men were randomised to Weight Watchers weight loss programme plus placebo versus the same weight loss programme plus testosterone. They also excluded men with high cardiovascular risk, due to a Food and Drug Administration [FDA] unproven concern about cardiovascular risk. "Testosterone may be dangerous in some of these men (59-75 years and obese) in real life," he pointed out.
The paper is currently in review but some preliminary findings were presented at a conference earlier this year. Dr Jayasena says: "If testosterone improves the prevention of type 2 diabetes during weight loss in men without hypogonadism, then that would challenge our understanding of how it works. However, testosterone is still not a treatment to prevent type 2 diabetes,"
To answer the question definitively, said Dr Jayasena, confirmatory data, mechanistic data, and safety data are needed.
COI: Dr Jayasena received an honorarium for speaking during a debate organised by the Society for Endocrinology and sponsored by Besins Healthcare. He has an investigator-led grant by Logixx Pharma Ltd.
Presented at the Royal Society of Medicine, Endocrinology and Diabetes section, entitled, EDN50: What's new in endocrinology and diabetes 2020? , Day 3. September 23, 2020
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