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  1. #1
    Senior Member Benson's Avatar
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    Default hCG administration, IM vs. SC injections

    This is sort of interesting...you have two studies of hCG administration routes and they appear to have completely opposite findings and a third which shows IM and SC administration of hCG to be equivalent...apparently it doesn't really matter how you inject it...

    Hum Reprod. 2003 Nov;18(11):2294-7.
    Bioavailability of hCG after intramuscular or subcutaneous injection in obese and non-obese women.

    Chan CC, Ng EH, Chan MM, Tang OS, Lau EY, Yeung WS, Ho PC.
    Source

    Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, SAR, China. cwcchan@graduate.hku.hk

    Abstract

    BACKGROUND:

    Obese women require higher gonadotrophin doses for ovarian stimulation and to trigger ovulation. The bioavailability of a drug is affected by its route of administration. Herein, the bioavailability of hCG was compared after intramuscular (i.m.) or subcutaneous (s.c.) injection in obese and non-obese women.
    METHODS:

    Twenty four Chinese women, 12 with a body mass index (BMI) >/==" BORDER="0">28 kg/m(2) and 12 with a BMI of 20-25 kg/m(2) were recruited as the obese and non-obese groups respectively. A single hCG injection was given intramuscularly on one occasion, and subcutaneously on a second occasion, separated by 4 weeks. Blood samples were taken at intervals for the pharmacokinetic study of hCG.
    RESULTS:

    Examination of the hCG plasma concentration-time curve showed the area under the curve (AUC) and maximum concentration (C(max)) of hCG to be significantly higher after i.m. injection than after s.c. injection in both the obese and non-obese groups. However, the AUC and C(max) values in obese women were significantly lower than in non-obese women, irrespective of whether i.m. or s.c. dosing was employed.
    CONCLUSIONS:

    Intramuscular dosing of hCG provided better bioavailability than s.c. dosing, but bioavailability was significantly less in obese women than in non-obese women.






    Fertil Steril. 2003 Apr;79(4):881-5.
    Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle.

    Stelling JR, Chapman ET, Frankfurter D, Harris DH, Oskowitz SP, Reindollar RH.
    Source

    Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston IVF, Boston, Massachusetts, USA. jstelling@pol.net

    Abstract

    OBJECTIVE:

    To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG.
    DESIGN:

    In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval.
    SETTING:

    This study was carried out in a university-affiliated IVF program.
    PATIENT(S):

    Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration.
    INTERVENTION(S):

    S.c. or i.m. injection of hCG.
    MAIN OUTCOME MEASURE(S):

    Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval.
    RESULT(S):

    There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L).
    CONCLUSION(S):

    After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.








    Hum Reprod. 1998 Jun;13(6):1461-4.
    A randomized three-way cross-over study in healthy pituitary-suppressed women to compare the bioavailability of human chorionic gonadotrophin (Pregnyl) after intramuscular and subcutaneous administration.

    Mannaerts BM, Geurts TB, Odink J.
    Source

    Clinical Development Department, NV Organon, Oss, The Netherlands.

    Abstract

    The objective of this study was to compare the bioavailability of s.c. and i.m. administration of human chorionic gonadotrophin (HCG; Pregnyl). In a randomized, single-centre, three-way cross-over study, 18 healthy pituitary-suppressed volunteers were assigned to single HCG injections of 5000 and 10,000 IU i.m. and 10,000 IU s.c. Rate (Cmax, t(max)) and extent [area under curve from zero to infinity (AUC(0-infinity))] of absorption of HCG were determined. Serum immunoactive HCG increased from 0.4-0.5 IU/l at baseline to mean peak concentrations, which were reached 20 h after injection of 156 IU/l with 5000 IU i.m., of 307 IU/l with 10,000 IU i.m. and of 339 IU/l with 10,000 IU s.c. Eight days after administration, < 10% of the maximum HCG activity was found for each regimen. The elimination half-life (t(1/2)) was on average 32-33 h, irrespective of the treatment regimen. Intramuscular and s.c. injections of 10,000 IU HCG were bioequivalent with respect to AUC(0-infinity). The Cmax and t(max) were also similar between the two administration routes but bioequivalence could not be proven due to intersubject variability. Intramuscular doses of 5000 IU and 10,000 IU HCG were dose-proportional. Since s.c. HCG is bioequivalent to i.m. HCG with respect to extent of absorption (its major pharmacokinetic variable) and is well tolerated, the s.c. administration route may be effectively and safely used in assisted reproduction. Moreover, since s.c. injection can be performed by the patients themselves, acceptability may be enhanced.
    Remember, believe none of what you hear and half of what you see...





  2. #2
    Senior Member Jakeshorts's Avatar
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    It'd be interesting to see the bf% of all these patients. In the first study they comment that the obese females absorbed s.c. poorly. I wonder what statistical impact this had on the the results. Perhaps if you are not obese there is no problem with s.c. administration.
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  3. #3
    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by Jakeshorts View Post
    It'd be interesting to see the bf% of all these patients. In the first study they comment that the obese females absorbed s.c. poorly. I wonder what statistical impact this had on the the results. Perhaps if you are not obese there is no problem with s.c. administration.
    It's also worth pointing out that hCG IM may have other drawbacks. I don't have a citation handy, but I seem to recall that injecting water-soluble compounds into muscle is far more damaging to the issue than injecting lipid-soluble compounds. I don't remember the mechanism, but it might have to do with osmotic effects.

    hCG is, of course, strictly water-soluble, as it's dissolved in water. Steroids, by contrast, are not.

    Might be something to think about. Personally I take hCG bi-weekly as part of TRT, and have always done SubQ. My testicles and sperm count are in excellent condition despite pinning 100mg testosterone/week.

  4. #4
    Senior Member Jakeshorts's Avatar
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    Quote Originally Posted by Ex Dubio View Post
    It's also worth pointing out that hCG IM may have other drawbacks. I don't have a citation handy, but I seem to recall that injecting water-soluble compounds into muscle is far more damaging to the issue than injecting lipid-soluble compounds. I don't remember the mechanism, but it might have to do with osmotic effects.

    hCG is, of course, strictly water-soluble, as it's dissolved in water. Steroids, by contrast, are not.

    Might be something to think about. Personally I take hCG bi-weekly as part of TRT, and have always done SubQ. My testicles and sperm count are in excellent condition despite pinning 100mg testosterone/week.
    The only thing I might counter with is that a dose of hCG is usually a relatively small quantity of liquid ~.2 or so of a mL.
    Resident Badger
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  5. #5
    Senior Member Benson's Avatar
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    Old study on the effects of hCG administration on body comp courtesy of ergo-log.

    HCG course can build muscles
    Remember, believe none of what you hear and half of what you see...





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    on a related note: do we have any evidence that HCG can be taken orally? I mean with the advent of the HCG diet many crooks are selling respective supplements, which are a ) underdosed and of which I b ) think that they will not hit the bloodstream intact, anyway (even if there was actually HCG in them)
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  7. #7
    Senior Member Benson's Avatar
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    Quote Originally Posted by physicus007 View Post
    on a related note: do we have any evidence that HCG can be taken orally?
    Seems incredibly unlikely that a peptide like hCG could survive digestion intact.
    Remember, believe none of what you hear and half of what you see...





  8. #8
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    Quote Originally Posted by Benson View Post
    Seems incredibly unlikely that a peptide like hCG could survive digestion intact.
    when I looked for an "easy to understand" scientific paper that would make clear that taking oral (homepathically dosed) HCG was bull to email it back to one of the SuppVersity readers who sent me a question in this regard, I happened onto the following study

    Hum Reprod. 2009 Mar;24(3):640-8. Epub 2008 Dec 16.
    Induction of ovulation by a potent, orally active, low molecular weight agonist (Org 43553) of the luteinizing hormone receptor.

    van de Lagemaat R, Timmers CM, Kelder J, van Koppen C, Mosselman S, Hanssen RG.
    Source

    Department of Pharmacology, Medicinal Chemistry, Molecular Design and Informatics, Molecular Pharmacology and Clinical Research, Schering-Plough Research Institute, PO Box 20, 5340 BH Oss, The Netherlands. ruud.vandelagemaat@spcorp.com

    Abstract

    BACKGROUND:

    In assisted reproductive technology, human chorionic gonadotrophin (hCG) is administered subcutaneously for the induction of oocyte maturation and ovulation. Our efforts to develop orally bioavailable luteinizing hormone (LH) receptor agonists have led to the discovery of Org 43553, a low molecular weight (LMW) LH receptor (LH-R) agonist.
    METHODS:

    Org 43553 was tested in vitro and in vivo in pre-clinical pharmacological models to demonstrate efficacy and oral availability.
    RESULTS:

    Org 43553 is a potent stimulator of the human LH-R in vitro (EC(50) 3.7 nM). In primary mouse Leydig cells, Org 43553 stimulated testosterone production. Pharmacokinetic analyses showed high oral bioavailability in rats (79%) and dogs (44%) with a shorter half-life compared with hCG (3.4 versus 5.6 h in the rat). Ovulation induction by Org 43553 was demonstrated in immature mice as well as in cyclic rats after single-dose oral administration (50 mg/kg). The ovulated oocytes were of good quality as demonstrated by successful fertilization and implantation of normal embryos. In male rats, testosterone production was substantially induced after oral administration.
    CONCLUSIONS:

    Org 43553 is the first LMW LH-R mimetic with demonstrated in vivo efficacy upon oral administration and could therefore replace subcutaneously administered hCG. The elimination half-life of Org 43553 is substantially shorter than hCG, which could potentially represent a clinical benefit in reducing the risk of ovarian hyperstimulation syndrome (OHSS).

    PMID:19088107 [PubMed - indexed for MEDLINE]
    So, even if pregnyl is not orally available, this Org 43553 appears to be.
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  9. #9
    Senior Member Benson's Avatar
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    Quote Originally Posted by physicus007 View Post
    So, even if pregnyl is not orally available, this Org 43553 appears to be.
    Nice find. Never heard of this before.
    Remember, believe none of what you hear and half of what you see...





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