How long for TRT to shut down spermatogenesis

[Appassionato]

As per title of the thread, does anyone know if there are studies showing how long it takes for exogenous testosterone to kill spermatogenesis?
As stated in other posts, I'm thinking of dropping HCG because it raises my E2 to 100+, giving me terrible sides even at doses as low as 50 IU 3x week and I can't manage it with an AI.
I would like to go with a protocol of daily injections of T enanthate and try to stay away from any AI, but at the same time, try to make kids in the next years until my spermatogenesis will definitely shut down.

P.S.: Freezing sperm is not an option for bio-ethical reasons.

 

[Systemlord]

You can add HCG and FSH injections to your TRT protocol when looking to have kids, until then you can do TRT in isolation.

 

[Appassionato]

You can add HCG and FSH injections to your TRT protocol when looking to have kids, until then you can do TRT in isolation.

Thanks for your reply Systemlord.
I forgot to mention that before, but I don't want to put any obstacle to how many kids I could have with my wife, which means I should run HCG all the time until my wife gets pregnant, stop with it and then repeat the procedure when she will be able to get pregnant again.
Something that would be obviously unsustainable for me for the months I'm on HCG, because I don't tolerate such high levels of E2. Also that would create a roller-coaster of hormonal changes throughout the years that I'm not willing to experience.

Other question would be, is FSH alone enough to keep fertility? If yes, does it raises E2 as well as HCG?

 

[HealthMan]

Thanks for your reply Systemlord.
I forgot to mention that before, but I don't want to put any obstacle to how many kids I could have with my wife, which means I should run HCG all the time until my wife gets pregnant, stop with it and then repeat the procedure when she will be able to get pregnant again.
Something that would be obviously unsustainable for me for the months I'm on HCG, because I don't tolerate such high levels of E2. Also that would create a roller-coaster of hormonal changes throughout the years that I'm not willing to experience.

Other question would be, is FSH alone enough to keep fertility? If yes, does it raises E2 as well as HCG?

FSH alone will not be enough for optimal spermatogenesis in the absence of LH. Intratesticular testosterone is necessary. FSH does not raise E2

 

[madman]

As per title of the thread, does anyone know if there are studies showing how long it takes for exogenous testosterone to kill spermatogenesis?
As stated in other posts, I'm thinking of dropping HCG because it raises my E2 to 100+, giving me terrible sides even at doses as low as 50 IU 3x week and I can't manage it with an AI.
I would like to go with a protocol of daily injections of T enanthate and try to stay away from any AI, but at the same time, try to make kids in the next years until my spermatogenesis will definitely shut down.

P.S.: Freezing sperm is not an option for bio-ethical reasons.

When starting trt use of exogenous testosterone will result in shutdown of ones hpta within 4-6 weeks and will have a negative effect on spermatogenesis and fertility within 4 months of use.



How testosterone inhibits spermatogenesis and fertility

Mechanism of action
Testosterone inhibits both GnRH and gonadotropin secretion. Exogenous administration of synthetic testosterone results in negative feedback on the hypothalamic-pituitary axis, inhibiting GnRH, leading to inhibition of FSH and LH production. As a result, intratesticular testosterone levels (ITT) and overall testosterone production decrease. Exogenous testosterone therapies can suppress ITT production to such a degree that spermatogenesis can be dramatically compromised at ITT concentrations to less than 20 ng/mL, even resulting in azoospermia (9-11) (Figure 3).

 

[Appassionato]

When starting trt use of exogenous testosterone will result in shutdown of ones hpta within 4-6 weeks and will have a negative effect on spermatogenesis and fertility within 4 months of use.



How testosterone inhibits spermatogenesis and fertility

Mechanism of action
Testosterone inhibits both GnRH and gonadotropin secretion. Exogenous administration of synthetic testosterone results in negative feedback on the hypothalamic-pituitary axis, inhibiting GnRH, leading to inhibition of FSH and LH production. As a result, intratesticular testosterone levels (ITT) and overall testosterone production decrease. Exogenous testosterone therapies can suppress ITT production to such a degree that spermatogenesis can be dramatically compromised at ITT concentrations to less than 20 ng/mL, even resulting in azoospermia (9-11) (Figure 3).





View attachment 7001

Thanks for the reply.
I've been without HCG from September 2017 until May 2018, when I've introduced it due to upcoming marriage. I managed to get my wife pregnant at the first attempt in June, even she was still with her period (last few days). Does that mean that 250 IU 3x week for 1 month were enough to restore my spermatogenesis?
Or that within 4 months you get a lowered motility and density, but not complete shutdown of spermatogenesis?

 

[HealthMan]

Thanks for the reply.
I've been without HCG from September 2017 until May 2018, when I've introduced it due to upcoming marriage. I managed to get my wife pregnant at the first attempt in June, even she was still with her period (last few days). Does that mean that 250 IU 3x week for 1 month were enough to restore my spermatogenesis?
Or that within 4 months you get a lowered motility and density, but not complete shutdown of spermatogenesis?

TRT does not necessarily cause infertility. Some men on TRT have normal sperm count even without HCG. You might be one of them.

 

[Appassionato]

TRT does not necessarily cause infertility. Some men on TRT have normal sperm count even without HCG. You might be one of them.

That's really interesting, since I will be doing just 10mg daily to get E2 in check without an AI. Do you have studying backing that claim up?

 

[HealthMan]

That's really interesting, since I will be doing just 10mg daily to get E2 in check without an AI. Do you have studying backing that claim up?

There are many studies out there. Because testosterone has been of interest as a male contraceptive method. It is not used as such for a reason. One example below

Progress and prospects in male hormonal contraception

 

[HealthMan]

In most cases men will have azoospermia or oligospermia. And some will have normal sperm count. Remember you can still make a women pregnant if you have oligospermia.

 

[Appassionato]

In most cases men will have azoospermia or oligospermia. And some will have normal sperm count. Remember you can still make a women pregnant if you have oligospermia.

The first study enrolled 271 subjects who were administered 200 mg testosterone enanthate by intramuscular injection weekly for 6 months [9]. Sixty percent of the men in this study became azoospermic, and an additional 30% became severely oligospermic. The fertility of 119 of the azoospermic men was then tested in a 12-month efficacy phase. In these couples, only one pregnancy occurred despite the cessation of other forms of birth control, corresponding to a rate of 0.8 pregnancies per 100 person-years.

That's interesting. So basically 60% became completely infertile, but one was still able to make his wife pregnant? And an additional 30% got their spermatogenesis severely impaired but not shutted down completely?

 

[HealthMan]

This is the problem. If you have little sperm (oligospermia) you can still get a woman pregnant. Dosage, interval, ester all seem to have an impact on sperm count as well. And a very small portion of men will still have normal sperm count. Oligospermia will make it much harder to make a woman pregnant but not impossible. After all.. all it takes is one sperm to reach the egg. Testosterone also impacts fertility other ways (not only by decreasing sperm count). It lowers motility, forward progression, increase the number of abnormally shaped sperm etc. All these play against the odds of making a baby

 

[HealthMan]

For example i know of various friends and friends of friends that got their wives pregnant while taking massive dosages of testosterone (for bodybuilding purposes). Not 1 or 2 cases. Several.

 

[Appassionato]

For example i know of various friends and friends of friends that got their wives pregnant while taking massive dosages of testosterone (for bodybuilding purposes). Not 1 or 2 cases. Several.

Thanks HealthMan, that was good news. I will discuss it next time with Dr. Saya if the once a week micro dose of exemestane doesn't work.

 

[madman]

In 1978, a newly available oral testosterone preparation known as testosterone undecanoate (TU) was investigated as a possible form for male contraception. The study found that regular testosterone use for 10 to 12 weeks causes suppression of sperm production, and even azoospermia, albeit inconsistently [24]. Ever since that study, testosterone has undergone extensive clinical trials as a hormonal method of male contraception and many have found testosterone to be efficacious, reversible and safe with minimal short-term side effects [23].





TESTOSTERONE AS A MALE CONTRACEPTIVE

Unfortunately, the contraceptive effect of testosterone is not reliable. This has been proven in multiple studies, including two by the World Health Organization (WHO) Task Force on Methods for the Regulation of Male Fertility [14,15,25]. These two studies found an azoospermia rate of 64% to 75% in 6 months with testosterone enanthate [6,7]. A sperm concentration of 3 million/mL was used as a threshold for effective suppression of spermatogenesis in this study [14,15]. In a Chinese study of a monthly intramuscular TU injection, an azoospermia rate of 93% to 98% was achieved after 6 months with 1 million/mL as the criteria for effective suppression [25,26]. The different rates of azoospermia can be explained by the variable criteria and by ethnic differences in testosterone response [26,27]. These studies confirm the effectiveness of testosterone as a contraceptive, and provides evidence that men who desire fertility should not be prescribed TRT. Even with this evidence, testosterone has not been approved by the USA Food and Drug Administration (FDA) for use as a contraceptive. In 2011, a phase II study for a combined TU/norethisterone enanthate formulation ended prematurely because of higher than anticipated adverse effects including mood changes (such as depression), increased libido, acne and weight gain [27,28].



FORMULATIONS OF TESTOSTERONE REPLACEMENT THERAPY

In terms of the contraceptive effect of the different formulations of testosterone, most research has shown that transdermal and intramuscular testosterone seem to be the strongest contraceptive formulations. The WHO and Chinese studies used testosterone enanthate and TU, respectively. The topical formulations of testosterone have variable contraceptive effects. The testosterone patch was shown to be an ineffective contraceptive [41] while the gel had mixed results [42,43].

However, the sample size for most of these studies are not large enough to truly assess the extent to which fecundity is affected. More research needs to be done to evaluate the contraceptive effect of the various formulations of testosterone.



USING TESTOSTERONE IN THE TREATMENT OF HYPOGONADISM IN MEN WHO DESIRE FERTILITY

Considering that there is abundant evidence demonstrating that TRT significantly decreases sperm production, it is important that clinicians consider the evidenced risks of male infertility before starting patients on TRT. It can be surprising to patients that testosterone can suppress fertility, in contrary to its stimulatory effects on libido and erectile function. The patient’s desire for fertility must be discussed in depth and established prior to initiating testosterone. The discussion must also include future thoughts on fertility. This will allow the physician to manage the timing of hypogonadism treatment, essentially balancing the alleviation of hypogonadal symptoms with the patient’s desires for fertility. This could also open discussion about cryopreservation of sperm as an option for the patient to preserve fertility further down the line.


Regardless, the recovery of spermatogenesis is unclear for patients on chronic TRT. Physicians should take caution when treating hypogonadism in men who desire future fertility, but also acknowledge the reversible azoospermia seen in controlled studies [51]. Adjunctive hCG and clomiphene can be used with TRT to maintain testicular size and intra-testicular testosterone concentrations [52]. Referral to a reproductive urologist should be considered in a male with low testosterone interested in fertility.





CONCLUSIONS

Testosterone therapy is a contraceptive, albeit a poor one. Men of reproductive age with low testosterone should be counseled on the adverse effects of TRT on fertility. Obtaining a semen analysis and possible cryopreservation of sperm should be offered if TRT is prescribed to men interested in preserving fertility. Options such as clomiphene citrate and hCG along with a referral to a reproductive urologist should be considered to naturally increase testosterone levels in those men with low testosterone who want to avoid TRT.

 

[Appassionato]

In 1978, a newly available oral testosterone preparation known as testosterone undecanoate (TU) was investigated as a possible form for male contraception. The study found that regular testosterone use for 10 to 12 weeks causes suppression of sperm production, and even azoospermia, albeit inconsistently [24]. Ever since that study, testosterone has undergone extensive clinical trials as a hormonal method of male contraception and many have found testosterone to be efficacious, reversible and safe with minimal short-term side effects [23].





TESTOSTERONE AS A MALE CONTRACEPTIVE

Unfortunately, the contraceptive effect of testosterone is not reliable. This has been proven in multiple studies, including two by the World Health Organization (WHO) Task Force on Methods for the Regulation of Male Fertility [14,15,25]. These two studies found an azoospermia rate of 64% to 75% in 6 months with testosterone enanthate [6,7]. A sperm concentration of 3 million/mL was used as a threshold for effective suppression of spermatogenesis in this study [14,15]. In a Chinese study of a monthly intramuscular TU injection, an azoospermia rate of 93% to 98% was achieved after 6 months with 1 million/mL as the criteria for effective suppression [25,26]. The different rates of azoospermia can be explained by the variable criteria and by ethnic differences in testosterone response [26,27]. These studies confirm the effectiveness of testosterone as a contraceptive, and provides evidence that men who desire fertility should not be prescribed TRT. Even with this evidence, testosterone has not been approved by the USA Food and Drug Administration (FDA) for use as a contraceptive. In 2011, a phase II study for a combined TU/norethisterone enanthate formulation ended prematurely because of higher than anticipated adverse effects including mood changes (such as depression), increased libido, acne and weight gain [27,28].



FORMULATIONS OF TESTOSTERONE REPLACEMENT THERAPY

In terms of the contraceptive effect of the different formulations of testosterone, most research has shown that transdermal and intramuscular testosterone seem to be the strongest contraceptive formulations. The WHO and Chinese studies used testosterone enanthate and TU, respectively. The topical formulations of testosterone have variable contraceptive effects. The testosterone patch was shown to be an ineffective contraceptive [41] while the gel had mixed results [42,43].

However, the sample size for most of these studies are not large enough to truly assess the extent to which fecundity is affected. More research needs to be done to evaluate the contraceptive effect of the various formulations of testosterone.



USING TESTOSTERONE IN THE TREATMENT OF HYPOGONADISM IN MEN WHO DESIRE FERTILITY

Considering that there is abundant evidence demonstrating that TRT significantly decreases sperm production, it is important that clinicians consider the evidenced risks of male infertility before starting patients on TRT. It can be surprising to patients that testosterone can suppress fertility, in contrary to its stimulatory effects on libido and erectile function. The patient’s desire for fertility must be discussed in depth and established prior to initiating testosterone. The discussion must also include future thoughts on fertility. This will allow the physician to manage the timing of hypogonadism treatment, essentially balancing the alleviation of hypogonadal symptoms with the patient’s desires for fertility. This could also open discussion about cryopreservation of sperm as an option for the patient to preserve fertility further down the line.


Regardless, the recovery of spermatogenesis is unclear for patients on chronic TRT. Physicians should take caution when treating hypogonadism in men who desire future fertility, but also acknowledge the reversible azoospermia seen in controlled studies [51]. Adjunctive hCG and clomiphene can be used with TRT to maintain testicular size and intra-testicular testosterone concentrations [52]. Referral to a reproductive urologist should be considered in a male with low testosterone interested in fertility.





CONCLUSIONS

Testosterone therapy is a contraceptive, albeit a poor one. Men of reproductive age with low testosterone should be counseled on the adverse effects of TRT on fertility. Obtaining a semen analysis and possible cryopreservation of sperm should be offered if TRT is prescribed to men interested in preserving fertility. Options such as clomiphene citrate and hCG along with a referral to a reproductive urologist should be considered to naturally increase testosterone levels in those men with low testosterone who want to avoid TRT.

Thanks.
Only caveat would be that Dr. Saya, for example, doesn't believe in clophiphene ability to keep fertility on men on TRT, according to his multiple years experience with patients.
I recall him saying that he had just a handful of patients on clomiphene and TRT keeping their spermatogenesis intact, possibly the same patients they would have it on TRT only anyway.