Successful treatment of anabolic steroid-induced azoospermia

thanks for this post nandi

this was actually a topic of discussion recently. perfect timing.

My biggest concern...haven't had my children yet...

Here is a little more background on the guy :

A 27-year-old woman was referred by her general practitioner because of a 1-year history of primary subfertility. Her 37-year-old husband, who worked as a security guard, was an amateur bodybuilder and had been lifting weights regularly for the past 20 years. He had taken part in several regional level bodybuilding competitions. He admitted starting to use anabolic steroids to enhance his muscle mass and strength 10 years previously. In this time he had used more than seven different types of steroid, all of which he obtained illegally.

He explained that he used steroid combinations for usually a few months before taking a short break and then commencing another course of steroids. The longest sustained course he took was for 8 months when he took twice weekly injections of testosterone cypionate (amounting to 1 gram per week) combined with both daily Dianabol tablets (methandrostenolone; he started on 10 mg/day and then increased the dose to 60 mg/day) and daily Anavar tablets (oxandrolone at 20 mg/day). He admitted to also using sustanon injections (testosterone propionate), Anadrol tablets (oxymetholone),Deca-Durabolin injections (nandrolone decanoate), and Primobolan Depot injections (methenolone enanthate).

During this period of time he had noticed a marked testicular atrophy as well as some erectile dysfunction (he described only partial erections which were difficult to maintain). He had not been on any medication in the past 1 year, had no other past medical history of note, and did not smoke or drink alcohol. On examination his skeletal muscle mass was found to be greatly increased. His secondary sexual characteristics were normal, although he had demonstrable gynecomastia. His testicles were of a low volume (2 to 3 mL) but were firm and nontender. There were no varicoceles present.

His serum gonadotropin and testosterone levels were low (FSH 0.5 U/L, LH 0.9 U/L, testosterone: 7 nmol/L). His serum prolactin level was normal. A urinary drug screen failed to identify any illicit substances; this was consistent with his story of having stopped taking the anabolic steroids 1 year previously when the couple decided to start a family. Three semen analyses (the third repeated 3 months after the second) showed a complete azoospermia with normal ejaculate volumes and liquefaction times.

We provided him with injections of human chorionic gonadotropins (hCG; Profasi; Serono) three times a week at a dose of 10,000 IU together with daily injections of human menopausal gonadotropin (hMG, Humegon; Organon) at a dose of 75 IU per day. After just 1 month of this treatment there was a dramatic improvement in his semen analyses, which showed a count of 8 million sperm/mL, motility of 48%, and 60% with normal morphology. His serum gonadotropin and androgen levels were normal at this time (FSH 5 U/L, LH 8 U/L, testosterone: 21 nmol/L). We continued this regimen for 2 months more and then rechecked his semen analyses. The sperm count was 23 million sperm/mL; motility was 45%, and 50% had normal morphology. We stopped the drug regimen and rechecked his semen analyses and serum testosterone levels 3 months later. The semen analysis was normal, as were the testosterone levels.

The goal of treating anabolic steroid�induced azoospermia is to restore endocrine function. Endocrine medications that are targeted specifically to ameliorate hypothalamic-pituitary-gonadal function have been well described and include testosterone esters, hCG, synthetic analogues of GnRH, and antiestrogens [5]. Human chorionic gonadotropin used alone has been reported to be successful in treating this group of patients [6 and 7]. In these cases, testicular function, once back to normal, continued even after the hCG was stopped. Although administering hMG seems appropriate given the hypogonadotropic results in this patient, it is not clear if exactly the same response could not have been achieved using hCG alone. Indeed the speed of recovery of endocrine function in our patient did not seem to be any faster than in reported cases using hCG alone [6].

There is no consensus on the ideal dosage of hCG or hMG in the treatment of this condition. We choose this dosage regimen empirically, with a mind to increase the dose further if subsequent semen analyses failed to show a response. Further study is needed to identify the optimal treatment in these patients

Does hmg stimulate sertoli cells? I always wondered if hcg and fsh would be the way to treat this.

10000 IU thrice weekkly?! I also wonder how necessary the HMG was. This is a treatment I may have to take.

quote:

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Does hmg stimulate sertoli cells? I always wondered if hcg and fsh would be the way to treat this

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Yes it does stimulate Sertoli cells, hopefully enhancing spermatogenesis. hCG stimulates the Leydig cells to produce testosterone. This is why the patient was given HMG. The couple was trying to conceive and the docs wanted to improve both sperm production (from Sertoli cells) and testosterone levels (to support sperm development and viability)

I spoke to an expert in invitro fertilization in primates, and she said that after trying both HCG and HMG, she now uses GnRH (which stimulates both FSH and LH) to induce ovulation in females and improve spermatogenesis in males with much better results, so this might be another or better option, but is not a drug that is readily available except to doctors. It also has the paradoxical effect of shutting down LH and FSH production if not dosed properly, so is probably not something to self administer unless you really knew what you were doing. In fact, this treatment has been advocated in the case of AAS induced HPT shutdown (note these authors use the synonym LH-RH for GnRH) (1)

(1) Int J Sports Med. 2003 Apr;24(3):195-6.

Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study.

van Breda E, Keizer HA, Kuipers H, Wolffenbuttel BH.

And of course the really important information was in the followup post by nandi wherein the sperm levels werre still up 3 months after cessation of treatment. That was my immediate concern after reading hte abstract. No, how about 6 months?

jb

Wouldn't 10000 IU three times per week actually be counterproductive? I would think it would completely shut down nat test production, thereby exacerbating azoospermia. Also, what about the estrogen?

I wonder, Is this just in people that didn't do any post cycle therapy? This treatment seems excessive.

Unfortunately, the text was not worded clearly at all. They could have meant 10,000 IU in divided doses. This would be more in line with what my PDR recommends for hypogonadism: 4000 IU injected three times per week for a total of 12,000 IU/week.

Doctors' writing skills have been known to suck.

And they did imply they were starting out low with the intention of increasing if the response was poor. So I am interpreting it as 10,000 IU in three divided doses. I could be wrong though.

I wonder how important the HMG is...

For Testosterone production it is not important at all. To induce spermatogenesis, FSH, either stimulated "naturally" by administering recombinant GnRH, or artificially in the form of HMG, really helps spermatogenesis, according to my resident fertility expert (sister in law at UC Davis). But her expertise is in the field of monkeys, who (according to her) often will have great difficulty breeding in captivity, due both to impaired fertility and an unwillingness to mate. Hence her in vitro work. From my limited knowledge gained primarily from reading up on it on fertility websites, it is pretty commonly used in both men and women. But again, in the study in question, recall the authors questioned whether it would have made a difference.

I don't think there is a one size fits all fertility treatment protocol. For instance, some women are able to conceive after a short course of clomid. Others require long protracted treatment with a variety of agents, and that often does not even work.

Great post Nandi,

As a guy that's planning on starting a family in the next few years I'm always interested in anything that may improve my fertility if something is ever amiss.

Now we just need to see hmg showing up on some lists!

I'd bet SWALE would prescribe it if you didn't mind paying his "consultation fee". We should try to get him to give a discount to CEM members. (SWALE, bro, are you listening? )

I think that's a fantastic idea, and when the times comes (hopefully in about 1 year...) I'll certainly go that route.