just use both, I think post cycle therapy (pct) is best when you use clomid and nolva together imo.
This is the common answer, I however, disagree completely.
THe following is what is believed by MOST bro's.
Clomid acts as an estrogen, rather than an antiestrogen, by sensitizing pituitary cells to the action of GnRH. Although tamoxifen is almost as effective as Clomid in binding to pituitary estrogen receptors, tamoxifen has little or no estrogenic activity in terms of its ability to enhance the GnRH-stimulated release of LH. The estrogenic action of Clomid at the pituitary represents a unique feature of this compound and that tamoxifen may be devoid of estrogenic activity at the pituitary level.
What is described above is also known as "estrogen priming," the concept that estrogen makes the pituitary more sensitive to GnRH from the hyp[othalamus, so that more LH is released for a given GnRH stimulus. This is well known to occur in females leading up to ovulation. Unlike females, however, men don't have a preovulatory period or spikes in LH. The research is fairly clear that estrogen priming does not occur in males. For starters, take a look at an authoritative reference work like Grossman's
Clinical Endocrinology, which states (pg. 99):
Progesterone, acting synergistically with oestrogens, exerts negative feedback on the hypothalamus during the luteal phase, thus limiting GnRH pulsatility and slowing LH pulse frequency. The mechanism of positive oestrogen feedback at the time of the LH surge has been much debated. There is now evidence that enhancement of both hypothalamic GnRH pulse generator activity and pituitary responsiveness to GnRH are involved. All species so far studied have shown an increased 'self-priming' effect of GnRH on the pituitary during the preovulatory period... In males, the situation is more straightforward. Since LH surges do not occur, only negative feedback effects are relevant. Testosterone (and its active metabolite dihydrotestosterone, DHT) exerts major suppressive effects on both LH and FSH secretion, largely by inhibiting the GnRH pulse frequency generator, but possibly also by direct pituitary actions. Oestrogens in the male reduce pituitary responsiveness to GnRH
That states pretty clearly that there is no priming in males, only negative feedback. The last emboldened sentence in this quote directly contradicts the statement made at the beginning of this post. If clomid were to produce estrogenic action in the pituitary, it would only serve to inhibit LH secretion.
Grossman's statement is corroborated by
the most recent research on the specific effects of androgens and estrogen on the pituitary and hypothalamus of healthy men. Here, it was shown that estrogenic action at the pituitary has an inhibitory effect on LH output. In other words, estrogen decreases pituitary sensitivity to GnRH. Estrogen does not produce positive feedback as seen in estrogen priming in females. The paper stated in its conclusion that "These data confirm previous work from our group which ... showed
[estrogen] has both hypothalamic and pituitary sites of negative feedback in the male." In fact, "negative feedback at the pituitary requires aromatization," as testosterone itself doesn't produce negative feedback at the pituitary.
This older paper had a very interesting finding:In other words, estrogen levels during brain development are responsible for the sex-specific differences in gonadotrophin secretion and estrogen feedback at the pituitary. The important point of this research is that males (with the exception of homosexuals) were not found to have any positive feedback from estrogen. Those results that were "strongly confirmed."
Finally, there's
this research, which couldn't have been any more relevant. It directly examined the effects of nolva and clomid on the pituitary of human males. They infused the men with 100 mcg of GnRH and then measured LH output from the pituitary. The men taking nolvadex at 20mg/day had a significantly increased LH response to GnRH. In contrast,
the men taking clomid had reduced LH output, a decreased sensitivity to GnRH. The researchers stated that "a role of the intrinsic estrogenic activity of Clomid which is practically absent in Tamoxifen seems the most probable explanation."
All in all, I don't understand the "BRO LORE" position for using clomid during post cycle therapy (pct). It assumes estrogen priming in males, yet both research and experts in endocrinology seem to squarely contradict the notion. Clomid appears to produce an estrogenic effect at the pituitary, yes, but the evidence shows that in males this serves to inhibit LH output in contrast to nolva. All else being equal, that would make the use of clomid inferior to nolva for purposes of post cycle therapy (pct).
