Hi guys
Found a study on the use of HCG during pct. Will post the link to the full study as well as some data I deemed most important. If you don´t feel like going through the data then just read my conclusion.
Gries JM, Munafo A, Porchet HC, Verotta D. Down-regulation models and modeling of testosterone production induced by recombinant human choriogonadotropin. J Pharmacol Exp Ther 1999;289(1):371-7
Down-Regulation Models and Modeling of Testosterone Production Induced by Recombinant Human Choriogonadotropin
Abstract
Chorionic gonadotropin (CG) is a glycoprotein hormone, whose action is mediated by the luteinizing hormone/CG receptor. Testosterone concentrations from six pituitary-desensitized, healthy male volunteers were obtained after four different administrations of recombinant-human CG (rhCG). We present a modeling study to provide a possible explanation for the observations that increased exposure to rhCG induces higher and then lower testosterone concentrations and that marked rebound effects are observed at the end of repeated administration of rhCG. We used semimechanistic models (in which flexible functions represent unknown parts of the models) to identify the relationship of rhCG concentrations to the testosterone levels. Based on the results obtained with the semimechanistic models, different mechanistic down-regulation models were devised and tested. The final model uses a one-compartment model to describe the endogenous production rate of testosterone; rhCG affects the production rate with a mechanism consistent with a two-site binding site, with effect proportional to one-site bound concentration. The modeling results indicate that when rhCG concentration increases, the testosterone production rate increases to 45 times the baseline value. However, at an rhCG concentration of more than about 30 IU/liter, the production rate decreases. Simulations showed that both dose and dosing interval profoundly influence testosterone response to rhCG.
Chorionic gonadotropin (CG) is structurally related to the pituitary hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The actions of LH and CG are mediated by the LH/CG receptor, which is a member of the superfamily of G protein-coupled receptors. The binding of LH and CG occurs with similar high affinity, and both hormones have similar potencies and efficacies in stimulating gonadal cells. Thus, at a cellular level, the two hormones are roughly equivalent. In vivo, the main difference is the much longer half-life of CG.
The primary physiological effect of the gonadotropins is the promotion of gametogenesis and/or gonadal steroid production. In the male, endogenous production of CG does not occur, and LH stimulates the de novo synthesis of androgens, primarily testosterone, by Leydig cells. The secreted testosterone is required for gametogenesis and for the maintenance of sexual libido and secondary sexual characteristics. CG is used primarily in females to trigger ovulation or to induce final follicular maturation before assisted reproduction techniques, and it is used for male infertility and cryptorchidism. Gonadotropins of urinary origin have been used for a long time. Recombinant forms of human LH and CG have been produced (in mammalian cells) and are being tested in clinical studies for human use; recombinant human FSH is available in several countries.
We present the modeling of recombinant human CG (rhCG) in male subjects under pituitary desensitization: the male volunteers previously received a gonadotropin-releasing hormone analog to suppress their secretion of gonadotropins, secondarily decreasing their testosterone secretion. Each volunteer in the study received rhCG via four different routes. The main feature of the data was that all doses induce an effect but that the intravenous route (associated with the highest drug concentrations) leads to the smallest response. To analyze these data, we applied a general approach to model complex drug dynamics (Verotta, 1995; Verotta and Sheiner, 1995) that allows testing for alternative functional forms within a particular model structure. This helps devise final models that appear to be consistent with the physiological characteristics of the LH/CG receptor.
We describe the study design; the model for drug dynamics, including a pharmacokinetic model; and the various semimechanistic and mechanistic pharmacodynamics models, and we present selected results.
Results
Figure 2
Mean testosterone and rhCG serum concentrations after 2500 IU of rhCG i.v., i.m., s.c., and s.c. repeated five times (every other day). Top, testosterone. Bottom, rhCG. The solid line (and circles) is for the s.c. dose repeated five times, the dotted line (and triangles) is for the single s.c. administration, the broken line (and plus) for the i.m. administration, and the long dashed line (and crosses) for the i.v. administration. The error bars represent ±1 S.E.M.
Figure 5
Simulation of testosterone production in response to different doses and schedules of rhCG (SC×5 route) obtained with the down-regulation model. Five s.c. administrations are given daily (top left), every other day (top right), every 4 days (bottom left), and weekly (bottom right). The solid, dotted, broken, long dashed, and longer dashed lines mark the concentration time course for 500, 1000, 2500, 5000, and 10,000 IU, respectively; the short (solid) bars indicate the time of dose.
Discussion
The simulated testosterone levels show that to reach a target testosterone concentration of 25 nmol/liter, a dose of 1000 IU of rhCG every other 4 days would be sufficient. A higher 2500 or 5000 IU dose would produce a slightly higher response, but the highest dose will produce a lesser response according to the model. Clearly, the predicted pattern of decreased response at high doses and the pronounced rebound effect at treatment cessation is intriguing.
My conclusion
Taking HCG at 500iu is sufficient to reach Testosterone Serum levels of 25nmol/L, but a dose of 1000iu EOD can produce much higher Test levels.
To get the best testosterone response is to take HCG @1000iu 5 times EOD.
To inject 5 times EOD is a lot of injections. You also get a very good response from 1000iu once EOD. This is the way I suggest taking HCG during PCT.
Yes it is only one study and yes it is old but I think it is relevant to us.
