Nolva, Clomid, or Both for PCT

[AnabolicDoc]

I'm starting to think we should all be doing nolva only for PCT, possibly coupled with a low dose AI. I need to do more research, however. I thought this thread might help me get new ideas to pursue.

I have no doubt that clomid works - there are hundreds of studies showing that it works well for hypogonadotropic hypigonadism. I just think that nolva may work better and if you are going to do both, then one should start with nolva only for a few weeks and then maybe add clomid. Also, possibly a low dose AI from the beginning as well.

Clomid's net effect at the pituitary is as an estrogen. When GnRH binds to its receptors in the pituitary it is affected by the level of estrogen (this includes SERMs acting as estrogen agonists). At the pituitary, GnRH will have an enhanced effect in the presence of estrogens IN WOMEN and this is called estrogen priming. However the opposite happens in men - in men, the presence of estrogen at the pituitary decreases the effectiveness of GnRH at the pituitary. That's why I think clomid may not be best for PCT, at least at the beginning. (Edit: this paragraph has been edited, it previously said LH where it currently says GnRH. When I re-read this, I realized that what I initially typed did not make sense.)

There are studies that show that estrogen priming occurs in some men, but only those who self-selected themselves as homosexual. I mention this bc I know ppl will come across those studies and I don't want to make this an issue of whether homosexuality is a choice or genetically determined. If anyone is curious as to my beliefs, PM me or start a separate thread and I will gladly share.

Another reason against the use of clomid at least initially is that it has been repeatedly shown that GnRH agonists, when used in hypogonadal men, demonstrate decreased effectiveness in the presence of clomid but increased effectiveness in the presence of tamoxifen.

Regarding references, I need to re-find all the studies as my Internet Explorer became unresponsive bc of all the windows I had opened. But I will eventually get to it.

Any thoughts?

Oh, last thing I was looking for the thread that supported the use of nolva and clomid, with explanations as to why it's so necessary, but I couldn't find it using the search engine and it's not a sticky. If anyone has the link, please share it. Thank you.

[jimmyinkedup]

The whole concept behind the nolva/clomid pct is the mechanism that clomid acts not only as an estrogen agonist but antagonist as well as it is made up of of both e and z isomer. The thought process of say a Dr Scally is that the combination of both, due to the agonist /antagonist activity of clomid is more effective that either alone. I posted a somewhat extensive explanation from Dr Scally in the PCT section at one point. I know Mickey Knox has the link - he has posted it several times. Anyway its in the pct section and is titled Why Nolva and Clomid.

[AnabolicDoc]

I read Dr. Scally's explanation on the forum that he is a member of as other ppl have challenged his belief on this as well. I understand his explanation, but it doesn't address the two main points of my original post.

[MickeyKnox]

Med Hypotheses. 2009 Jun;72(6):723-8. Epub 2009 Feb 23.
Anabolic steroid -induced hypogonadism--towards a unified hypothesis of anabolic steroid action.
Tan RS, Scally MC.

Source
HPT/Axis Inc., 1660 Beaconshire Road, Houston, TX 77077, USA.

Abstract

Anabolic steroid-induced hypogonadism (ASIH) is the functional incompetence of the testes with subnormal or impaired production of testosterone and/or spermatozoa due to administration of androgens or anabolic steroids . Anabolic-androgenic steroid (AAS), both prescription and nonprescription, use is a cause of ASIH. Current AAS use includes prescribing for wasting associated conditions. Nonprescription AAS use is also believed to lead to AAS dependency or addiction. Together these two uses account for more than four million males taking AAS in one form or another for a limited duration. While both of these uses deal with the effects of AAS administration they do not account for the period after AAS cessation. The signs and symptoms of ASIH directly impact the observation of an increase in muscle mass and muscle strength from AAS administration and also reflect what is believed to demonstrate AAS dependency. More significantly, AAS prescribing after cessation adds the comorbid condition of hypogonadism to their already existing chronic illness. ASIH is critical towards any future planned use of AAS or similar compound to effect positive changes in muscle mass and muscle strength as well as an understanding for what has been termed anabolic steroid dependency. The further understanding and treatments that mitigate or prevent ASIH could contribute to androgen therapies for wasting associated diseases and stopping nonprescription AAS use. This paper proposes a unified hypothesis that the net effects for anabolic steroid administration must necessarily include the period after their cessation or ASIH.

PMID: 19231088 [PubMed - indexed for MEDLINE]

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 LHsecretion.

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
[63–67].

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 anabolic–androgenic 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 [70–73]. Clomiphene is a mixture of the trans (enclomiphene) and is (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.


"Clomiphene is an antiestrogen, which decreases the estrogen effect in the body. It has a dual effect by stimulating the hypothalamic pituitary area and it has an antiestrogenic effect, so that it decreases the effect of estrogen in the body. Tamoxifen is more of a strict antiestrogen; it decreases the effect of estrogen in the body, and potentiates the action of clomiphene. Tamoxifen and clomiphene citrate compete with estrogen for estrogen receptor binding sites, thus eliminating excess estrogen circulation at the level of the hypothalamus and pituitary, allowing gonadotropin production to resume. Administering them together produces an elevation of LH and secondary gonadal sex hormones. " Dr Michael Scally

[AnabolicDoc]

Thanks Mickey, I'll read this as soon as I get a chance. I appreciate it.

[MickeyKnox]

Youre welcome Doc.

[jimmyinkedup]

Thanks Mick!

[MickeyKnox]

You bet! ^^