hackskii

asih.net
Medical Doctor
Location: Texas



Re: Clomid and Novadex

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The administration of antiestrogens is a common treatment because anti estrogens interfere with the normal negative feedback of sex steroids at hypothalamic and pituitary levels in order to increase endogenous gonadotropin-releasing hormone secretion from the hypothalamus and FSH and LH secretion directly from the pituitary. In turn, FSH and LH stimulate Leydig cells in the testes, and this has been claimed to lead to increased local testosterone production, thereby boosting spermatogenesis with a possible improvement in fertility. There may also be a direct effect of antiestrogens on testicular spermatogenesis or steroidogenesis.

Clomiphene is a synthetic derivative an estrogen. Clomid is a mixed agonist/antagonist for the estradiol receptor. Tamoxifen is a pure estradiol receptor antagonist. 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.

Perusal of the literature thus indicates that clomiphene acts in several ways in the human male; (a) due to its similarity of structure to stilbesterol it binds with receptor sites in the hypothalamus and pituitary, (b) It stimulates gonadotrophin secretion by acting on the hypothalamo-hypophyseal system, (c) the inhibitory effects of high levels of circulating estrogens (produced under the influence of clomiphene) on hypothalamo-hypophyseal axis are possibly prevented by its potent antiestrogenic behaviour. The result of these varied effects of clomiphene is an overall increase in gonadotrophin and estrogen secretion and accounts for their increase under clinical conditions.

In one study the administration of tamoxifen, 20 mg/day for 10 days, to normal males produced a moderate increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels, comparable to the effect of 150 mg of clomiphene citrate (Clomid). Treatment of patients with "idiopathic" oligospermia for 6 to 9 months resulted in a significant increase in gonadotropin, testosterone, and estradiol levels.

Cochran database summary showed ten studies involving 738 men were included. Five of the trials did not specify method of randomization. Antiestrogens had a positive effect on endocrinal outcomes, such as serum testosterone levels. Antiestrogens appear to have a beneficial effect on endocrinal outcomes, but there is not enough evidence to evaluate the use of antiestrogens for increasing the fertility of males with idiopathic oligo-asthenospermia.

In the over one-thousand patiemts I have treated for HPTA normalization after AAS cessation i have used the combination of clomiphene citrate and tamoxifen. I have used clomiphene citrate alone in many cases. I added tamoxifen to the protocol to see if I could get a better clinical response. This seemed to be the case although I have not had the opportunity to evaluate the data. When both compounds are used the clomiphene citrate is discontinued first and the tamozifen is continued for 2 more weeks. as I stated in the post on hCG injections it is imperative to be tested while on the medications. thus one would be tested ~3-5 days before the tamoxifen expires. In the 1st stage described in the hCG post one tests for testosterone only. the serum T level determines whether or not the hCG is halted. In the typical situation the hCG is stopped and the CC & tamoxifen continued. the lab tests at the end of the oral meds is LH & T.
I hope this is of some assistance.

Peace.

Mike

__________________
Scott

hackskii

This dude is a doc and is in some kind of trouble but he is posting so I am copying

asih.net
Medical Doctor

Re: Injecting HCG?

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One should always inject hCG subcutaneously. The simplest reason is the comfort of the injection; less trauma to tissues; and decreased risk of infection. SC v IM are equally effective. As far as the kinetics of the injections one would expect them to be fairly similar. the reason why testosterone preparations last a longer time is due to the depot (oil) in which they are injected. hCG is soluble in water and will therefore be absorbed quickly. Other considerations are the weight of the individual. There are clinical indicators to monitor while taking hCG. If the hCG is being used for HPTA normalization a serum testosterone ashould be obtained while taking hCG and not after. this is critical and important for successful HPTA normalization.

Weissman, A., S. Lurie, et al. (1996). "Human chorionic gonadotropin: pharmacokinetics of subcutaneous administration." Gynecol Endocrinol 10(4): 273-6.
The objective of the present study was to evaluate the pharmacokinetics of human chorionic gonadotropin (hCG) following different regimens of subcutaneous and intramuscular single-dose administration. Two hypogonadotropic hypogonadal volunteers received hCG injections without prior ovarian stimulation. The regimens included a single dose of 10,000 IU hCG either subcutaneously or intramuscularly, or 5000 IU hCG intramuscularly. Serum beta-hCG concentrations were measured periodically up to 13 days after hCG administration. Each of the three regimens exhibit a similar pharmacokinetic profile and the highest serum beta-hCG concentrations were achieved with a dose of 10,000 IU administered subcutaneously. Seven days after hCG administration beta-hCG was detectable only after subcutaneous or intramuscular administration of 10,000 IU, but not after a single intramuscular injection of 5000 IU. From the preliminary results of the study it is suggested that a single intramuscular dose of 5000 IU hCG might be sufficient to trigger ovulation, but for luteal-phase support a higher dose may be needed. Subcutaneous administration of hCG for the induction of ovulation or luteal-phase support in gonadotropin-induced cycles is feasible and might offer a better tolerance and cost-effectiveness of infertility treatments, leading to their further simplification.

Trinchard-Lugan, I., A. Khan, et al. (2002). "Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers." Reprod Biomed Online 4(2): 106-15.
The pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin (rHCG) were investigated in three studies of healthy volunteers. After single intravenous doses of 25, 250 and 1000 microg, rHCG and urinary HCG (uHCG) showed linear pharmacokinetics described by a bi-exponential model, although the area under the curve (AUC) for uHCG was ~29% lower than for rHCG. After intramuscular or subcutaneous administration (absolute bioavailability, 40-50% for both), rHCG pharmacokinetics could be described by a first-order absorption, one-compartment model. During multiple subcutaneous dosing, the amount of HCG increased by approximately1.7-fold. A comparison of liquid and freeze-dried rHCG and freeze-dried uHCG showed pharmacokinetic bioequivalence. In down-regulated male subjects, single doses of 125 microg rHCG, given intravenously, intramuscularly or subcutaneously, produced comparable increases in serum testosterone, inhibin and 17beta-oestradiol, with little further increase during repeated subcutaneous administration (in female subjects, this produced a sustained comparable increase in serum androstenedione and testosterone concentrations). In conclusion, the pharmacokinetics and pharmacodynamics of rHCG are similar to those of uHCG and are not affected by the use of different formulations. In healthy subjects, rHCG produces pharmacodynamic responses consistent with HCG physiology and is suitable for use in the same clinical indications as uHCG. The secured source and high purity of rHCG may offer important advantages.

Burgues, S. and M. D. Calderon (1997). "Subcutaneous self-administration of highly purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism. Spanish Collaborative Group on Male Hypogonadotropic Hypogonadism." Hum Reprod 12(5): 980-6.
The efficacy and safety of highly purified follicle stimulating hormone (FSH) associated with human chorionic gonadotrophin (HCG) was studied in 60 men with hypogonadotrophic hypogonadism. Of these men, 16 suffered from Kallmann's syndrome, 19 from idiopathic hypogonadotrophic hypogonadism and 25 from hypopituitarism. Basal testosterone concentrations were found to be far below the normal range. At baseline, 26 patients were able to ejaculate and all of them showed azoospermia, while the remaining patients were aspermic. All patients self-administered s.c. injections of FSH (150 IU x three/week) and HCG (2500 IU x two/week) for at least 6 months and underwent periodic assessments of testicular function. Testosterone concentrations increased rapidly during treatment and all but one patient reached normal values. Testicular volume showed a sustained increase reaching almost 3-fold its baseline value. At the end of treatment, 48 patients (80.0%) had achieved a positive sperm count. The maximum sperm concentration during treatment was 24.5 +/- 8.1 x 10(6)/ml (mean +/- SEM). The median time to induce spermatogenesis was 5 months. Eleven patients reported adverse events, generally not related to treatment. Three patients experienced gynaecomastia. No local reactions at injection site were observed. In conclusion, the s.c. self-administration of highly purified FSH + HCG was well tolerated and effective in stimulating spermatogenesis and steroidogenesis in these patients.

Jones, T. H., J. F. Darne, et al. (1994). "Diurnal rhythm of testosterone induced by human chorionic gonadotrophin (hCG) therapy in isolated hypogonadotrophic hypogonadism: a comparison between subcutaneous and intramuscular hCG administration." Eur J Endocrinol 131(2): 173-8.
When human chorionic gonadotrophin (hCG) is used to stimulate testosterone synthesis and release in males with hypogonadotrophic hypogonadism, it is administered two or three times weekly by intramuscular injection. We have compared the pharmacokinetics of a twice weekly standard dose of hCG (5000 U) given for the first week by intramuscular injection and in the second week by self-administered subcutaneous injection. The patients studied had Kallmann's syndrome, isolated idiopathic hypogonadotrophic hypogonadism or post-traumatic isolated hypogonadotrophic hypogonadism. Salivary testosterone was collected twice daily at 08.00 h and 20.00 h, and serum testosterone was collected after 0, 24 h, 72 h, 120 h and 168 h each week. The cumulated serum and salivary testosterone levels were comparable on both intramuscular and subcutaneous hCG. In normal males there is diurnal variation in testosterone, with peak serum levels in the morning falling to a nadir in the evening. The exact nature and controlling factors of this circadian rhythm have not been established. In four of the subjects, the twice weekly hCG injections, either subcutaneous or intramuscular, produced a regular testosterone diurnal rhythm. The other four patients had fluctuations in testosterone but with no strict diurnal pattern. This study provides evidence that the luteinizing hormone-like action of hCG is necessary to prime the circadian rhythm but only a single bolus of hCG is sufficient to induce the rhythm in the absence of endogenous gonadotrophin production. In conclusion, self-administered subcutaneous hCG is safe and produces comparable levels of serum and salivary testosterone to that administered by the intramuscular route. Moreover, it was very well accepted by the patients and was preferred to conventional treatments. Human hCG in some patients with hypogonadotrophic hypogonadism produces normal physiological changes in daily testosterone levels.

Saal, W., H. J. Glowania, et al. (1991). "Pharmacodynamics and pharmacokinetics after subcutaneous and intramuscular injection of human chorionic gonadotropin." Fertil Steril 56(2): 225-9.
OBJECTIVE: The pharmacokinetics and efficiency of human chorionic gonadotropin (hCG) after subcutaneous (SC) injection was to clarify in comparison with the intramuscular (IM) mode of administration. DESIGN: In a prospective study, the pharmacokinetics of hCG and the response of serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) after an IM and SC injection of 5,000 IU hCG were evaluated up to 144 hours in two randomized groups. SETTING: The study was carried out in a clinical dermatology department providing tertiary care. PARTICIPANTS: Twenty-four healthy male volunteers with a mean age of 22.7 +/- 4.3 years were divided into two groups. INTERVENTIONS: Human chorionic gonadotropin (5,000 IU) was injected IM or SC. MAIN OUTCOME MEASURE: Serum concentration of /b-hCG, T, LH, and FSH were evaluated after IM and SC administration of hCG. Differences between the two groups were determined by t-test. RESULTS: Compared with IM administration of hCG, peak serum drug concentration was significantly delayed (P = 0.01) and serum half-life was prolonged (P = 0.01) after SC injection; however, T, LH, and FSH responses were identical. CONCLUSIONS: Subcutaneous application of 5,000 IU hCG is as effective as IM administration in terms of steroidogenesis.

Hope this helps.

Mike

__________________
Scott

John

nice post, informative.

hackskii

This dude is a doc on another board.
I am pumping this guy for info hard.
I hope he can answer some of my questions.

Sent him a little PM too.

This dude lost his license trying to help dudes.
He is bankrupt, penniless and full of information.

I hope he gets back to me on my questions.

__________________
Scott