Future treatments
A treatment goal of HPTA restoration will have its basis in the
regulation and control of testosterone production. The HPTA has
two components, both spermatogenesis and testosterone production.
In males, luteinizing hormone (LH) secretion by the pituitary
positively stimulates testicular testosterone (T) production; follicle-
stimulating hormone (FSH) stimulates testicular spermatozoa
production. The pulsatile secretion of gonadotropin-releasing hormone
(GnRH) from the hypothalamus stimulates LH and FSH
secretion. In general, absent FSH, there is no spermatozoa production;
absent LH, there is no testosterone production. Regulation of
the secretion of GnRH, FSH, and LH occurs partially by the negative
feedback of testosterone and estradiol at the level of the hypothalamo-
pituitary. Estradiol has a much larger, inhibitory effect than
testosterone, being 200-fold more effective in suppressing LH
secretion [5761].
In the case of ASIH, where the individual suffers from functional
hypogonadism and the belief for eventual return of function, treatment
is directed at HPTA restoration. A medical quandary for physicians
presented with hypogonadal patients secondary to AAS
administration is there is currently no FDA approved drug to restore
HPTA function. Standard treatment to this point has been testosterone
replacement therapy (TRT), human chorionic
gonadotropin (hCG), conservative therapy (watchful waiting or
do nothing), or off-label prescribing of aromatase inhibitors or
selective estrogen receptor modulators (SERM).
The primary drawback of testosterone replacement and hCG
administration is that this therapy is infinite in nature. These treatments
will remedy the signs and symptoms associated with hypogonadism,
but do not alleviate the need for a life-long commitment
to therapy. Further, administration serves to further HPTA suppression.
Conservative therapy (watchful waiting or do nothing) is
the probably worst case option as this does nothing to treat the patient
with ASIH. Also, conservative therapy will have the undesirable
result of the nonprescription AAS user to return to AAS use
as a means to avoid ASIH signs and symptoms.
The aromatase inhibitors demonstrate the ability to cause an
elevation of the gonadotropins and secondarily serum testosterone
[62]. The administration of SERMs is a common treatment in attempts
to restore the HPTA because they increase LH secretion
from the pituitary that leads to increased local testosterone production
[6367].
Guay has used clomiphene citrate as therapy for erection dysfunction
and secondary hypogonadism. Patients received clomiphene
citrate 50 mg per day for 4 months in an attempt to raise
their testosterone level [68]. Clomiphene has been reported in a
case study to reverse andropause secondary to anabolicandrogenic
steroid use [69]. The patient received clomiphene citrate
50 mg twice per day in an attempt to raise his testosterone level.
The patient when followed up after two months had a relapse,
tiredness and loss of libido, after discontinuing clomiphene citrate.
There are case study reports demonstrating the effectiveness of
the combination of clomiphene and tamoxifen in HPTA restoration
after stopping AAS administration [7073]. Clomiphene is a mixture
of the trans (enclomiphene) and cis (zuclomiphene) enantiomers,
which have opposite effects upon the estradiol receptor
[74]. Enclomiphene is an estradiol antagonist, while zuclomiphene
is an estradiol agonist. The addition of tamoxifen to clomiphene
might be expected to increase the overall antagonism of the estradiol
receptor. Enclomiphene alone might be a good candidate to restore
HPTA function.
