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.
