Book - PCT/AIH

[Michael Scally MD]

Q: Can hCG be administered by routes other than by injection?

A: Claims that oral, sublingual, or intranasal HCG are as effective as when hCG is given by injection are marketing attempts intended to deceive scientifically unsophisticated consumers. As added proof of its effectiveness, people point to a patent(s). Bottom line, the only effective and safe way to receive the benefits of hCG is by injection. To believe otherwise only indicates your gullibility and ignorance. And, a patent is meaningless!

What I find particularly amazing is the number of people that buy into this crap despite the overwhelming evidence against oral/sublingual hCG and the hCG diet. For those of you that have bought or are buying into this scam, it is time for a reality check. How many other things are you being scammed on? Any physician that uses or promotes this idea is a quack, pure and simple.

There is one report by a self-promoter. And even here they did not detect hCG in the serum after administration. UTILITY OF AN ORAL PRESENTATION OF HCG (HUMAN CHORIOGONADOTROPIN) FOR THE MANAGEMENT OF OBESITY: A DOUBLE-BLIND STUDY - Utility of an oral presentation of hCG; http://www.hcgobesity.org/research/D..._Study_hCG.pdf

There is so much money to be made by a route other than injection for glycoprotein(s). PhRMA has been trying for years to develop an inhalational form of Insulin, a much smaller drug. The problems for this much smaller drug have proven insurmountable to the largest companies with $$$.

 

[Michael Scally MD]

Q: Is rectal administration of hCG available?

A: No. In 2002, investigators reported in a rabbit study the successful use of rectal suppositories for hCG administration. This study has both never been repeated (probably for good reason) and never attempted in humans!

A look at the study reveals a number of reasons why this would be unwieldy in humans and possibly even dangerous, harmful, or deadly. In the rabbit study, hCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4000 IU/kg body weight). To enhance the rectal absorption of hCG, the effectiveness of its coadministration with ?-cyclodextrin (?-CyD), an absorption-enhancing agent, was performed. hCG 4000 IU/kg body weight) was detected in plasma following coadministration of hCG and ?-cyclodextrin (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of ?-cyclodextrin.

There are two very significant hurdles to this study. One is dosing. The other potentially lethal.

1. The dose was 4,000 IU/Kg body weight. For the typical male (70-80 Kg), this would mean an hCG dose of 28,000-32,000 IU. If that does not stop you in your tracks, the next concern will certainly maker anyone think twice!

2. As the study showed, rectal hCG administration was effective only in the presence of ?-cyclodextrin. And, apparently the more ?-cyclodextrin the better. While the exact mechanism is unknown, it is accepted that one of the proposed mechanisms is compromising the integrity of the mucosal membrane.

Does that need repeating? – “[C]ompromising the integrity of the mucosal membrane.”

No, Thank You.


Kowari K, Hirosawa I, Kurai H, Utoguchi N, Fujii M, Watanabe Y. Pharmacokinetics and Pharmacodynamics of Human Chorionic Gonadotropin (hCG) after Rectal Administration of Hollow-Type Suppositories Containing hCG. Biological and Pharmaceutical Bulletin 2002;25(5):678-81. https://www.jstage.jst.go.jp/article/bpb/25/5/25_5_678/_article

To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity.

To enhance the rectal absorption of hCG, the effectiveness of its coadministration with ?-cyclodextrin (?-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and ?-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of ?-CyD. The AUC0?48 observed after coadministration of hCG and ?-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and ?-CyD at 10 mg/kg body weight.

HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2±3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration.

On the other hand, the maximum level of testosterone concentration (40.0±12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with ?-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0±11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4±0.9 ng/ml) observed before the administration.

These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.

 

[Michael Scally MD]

AAS Addiction Fail – A Case of Circular Logic

In 2009, the following was part of the response to a letter challenging the criteria proposed for AAS Addiction in the upcoming DSM-V. And despite these efforts, the DSM-V did NOT include a separate category for AAS Addiction. As has been the case for many decades, the overwhelming research demonstrates AAS Addiction to be a myth.

Moreover, as the response shows the proponents of AAS Addiction wish to include AIH as part of AAS Addiction. One must seriously question their desire to include AIH. Also, their understanding for the HPTA is wanting. AIH occurs 100% of the time after stopping androgens, not jus after “chronic anabolic-androgenic steroid exposure.” The variables are the duration and severity.

This post only addresses their concept for withdrawal, but equally confusing is their refusal to take into account the well-known and well-described actions for AAS upon muscle mass and strength. IMO, they are still living in the past and changing the goal posts for AAS Addiction in order to save face and their failed efforts over the past decades to have this myth recognized. Further,

Are they suggesting that there be NO testing for AIH before placing the label of AAS Addiction?

Are they suggesting to totally ignoring the real disease AIH, which is recognized by all of the medical community?

Are they purposefully ignoring the fact that no study on AAS Addiction accounted for AIH?

We agree with virtually all of the points raised by Drs. Scally and Tan, except for a minor semantic issue regarding their suggestion that anabolic steroid-induced hypogonadism represents a possible “confounding variable” in the diagnosis of anabolic-androgenic steroid dependence.

To explain, we need to carefully define our terms. Anabolic steroid- induced hypogonadism is certainly a common physiologic response to chronic anabolic-androgenic steroid exposure, and it may contribute to anabolic-androgenic steroid withdrawal symptoms. Duh, you think?

Withdrawal symptoms, in turn, are a cluster of physical and psychological symptoms that may occur after discontinuing a drug that induces physiological dependence. Withdrawal symptoms are only one of the seven DSM-IV criteria for substance dependence and are neither necessary nor sufficient for a DSM-IV diagnosis of substance dependence.

With these definitions in mind, then, we would say that anabolic steroid-induced hypogonadism represents simply one underlying mechanism for the etiology of anabolic- androgenic steroid withdrawal symptoms and should not be considered a confounder for making a DSM-IV diagnosis of anabolic-androgenic steroid dependence.

http://www.focus.psychiatryonline.org/article.aspx?articleid=101236 (PsychiatryOnline | American Journal of Psychiatry | Dr. Pope Replies)

 

[CensoredBoardsSuck]

AAS Addiction Fail – A Case of Circular Logic

In 2009, the following was part of the response to a letter challenging the criteria proposed for AAS Addiction in the upcoming DSM-V. And despite these efforts, the DSM-V did NOT include a separate category for AAS Addiction. As has been the case for many decades, the overwhelming research demonstrates AAS Addiction to be a myth.

You're not the only one left shaking your head at the new DSM-V.
Allen Frances: Terrible News: DSM-5 Refuses to Reduce Overdiagnosis of 'Somatic Symptom Disorder'

We have failed, and DSM-5 has failed us. For reasons that I can't begin to fathom, DSM-5 has decided to proceed on its mindless and irresponsible course. The sad result will be the mislabeling of potentially millions of people with a fake mental disorder that is unsupported by science and flies in the face of common sense."

Allen Frances is a professor emeritus at Duke University and was the chairman of the DSM-IV task force.​

Unfortunate, but not surprising. When diagnostic criteria is based on consensus rather than scientific evidence, this is what you get. Even the National Institute of Mental Health has rejected the APA's cash cow and proposed the creation of an alternative manual. That pretty well says it all, IMO.

 

[Dr JIM]

I've no doubt the effects of AAS can be "habit forming" but an addiction! LMAO!

 

[Michael Scally MD]

Q: Other than AAS, what drugs have been shown to cause hypogonadism or reduce testosterone production?

A: Among the medications known to alter the hypothalamic-pituitary-gonadal axis are spironolactone, ketoconazole, cimetidine, flutamide, cyproterone, corticosteroids, ethanol, anticonvulsants, immunosuppressants, opiates, and psychotropic medications. Of particular note, spironolactone and ketoconazole are used for hair loss.

 

[Mr. Joe]

Will there be a section in your book discussing the current literature on the molecular mechanisms responsible for AIH and more interestingly, recovery from AIH. I would be interested to read about the molecular physiology behind why some of us bounce back quickly and others can't seem to restart. Furthermore, what changes are occurring overtime which make restarting more difficult for those who continue to cycle, to what extent is the repeated shutting down of HPTA to blame, vs. normal physiologic changes due to aging.

 

[Michael Scally MD]

Prices for 1 kit of 10000 units/vial Pregnyl (brand) [~$70]
Pregnyl Prices, Coupons and Information - GoodRx

 

[Michael Scally MD]

I believe you are all aware of my efforts in having this recognized. Unfortunately, my efforts at treatment went punished.

Coward RM, Rajanahally S, Kovac JR, Smith RP, Pastuszak AW, Lipshultz LI. Anabolic steroid-induced hypogonadism in young men. J Urol. Elsevier

PURPOSE: Use of anabolic androgenic steroids (AAS) has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism, a very heterogeneous population of men is now being evaluated. Within this larger population of patients, the existence of anabolic steroid-induced hypogonadism (ASIH), whether transient or permanent, should now be considered.

MATERIALS AND METHODS: An initial retrospective database analysis of all patients (2005-2010, n=6033) seeking treatment for hypogonadism was conducted. Subsequently, an anonymous survey was distributed in 2012 to established patients undergoing testosterone replacement therapy (TRT).

RESULTS: Profound hypogonadism, defined as a testosterone =50 ng/dL, was identified in 1.6% (n=97) of the large retrospective cohort initially reviewed. The most common etiology was prior AAS exposure, identified in 43% (42/97) of men. Because of this surprising data, a follow-up anonymous survey of our current hypogonadal patient population (n=382; mean age 49.2+/-13.0 years) was then performed which identified 20.9% of patients (n=80; mean age 40.4+/-8.4 years) with prior AAS exposure. Hypogonadal men <50 years old were greater than 10 times more likely to have prior AAS exposure than men >50 (OR 10.16, 95% CI 4.90-21.08). Prior AAS use was significantly negatively correlated with education level (rho=-0.160, p=0.002) and number of children (rho=-0.281, p<0.0001).

CONCLUSIONS: Prior AAS use is common in young men seeking treatment for symptomatic hypogonadism, and ASIH is the most common etiology of profound hypogonadism. These findings suggest a necessary refocused approach in the evaluation and treatment paradigms of young hypogonadal men.

 

[Michael Scally MD]

Re: The Endocrine Society's Annual Meeting - ENDO2013

[In other words, the HPTA was equally suppressed in both populations! Or, there would be a significant difference in TRT dose.]

Testosterone Replacement Therapy In Hypogonadal Men: The Contribution Of Endogenous Testosterone Production
http://edrv.endojournals.org/cgi/content/meeting_abstract/34/03_MeetingAbstracts/SAT-290 (Testosterone replacement therapy in hypogonadal men: The contribution of endogenous testosterone production -- Muram and Ni 34 (3): SAT-290 -- Endocrine Reviews)

Objective: This post-hoc analysis investigated the effects of endogenous testosterone (T) production reflected by baseline testosterone levels on testosterone replacement therapy (TRT) in hypogonadal men.

Design: In this open-label titration trial, 2% T topical solution was applied to the axillae daily for 120 days. Dose adjustments were allowed on Days 45 and 90 to maintain T within physiological range (300 - 1050 ng/dL).

Patients: Males (N = 155) over 18 years of age with hypogonadism (T < 300 ng/dL).
Measurements: Serum T levels were measured at days 15, 60 and 120. Subjects were divided by T-level at baseline (T < 230 ng/dL and T 230 ng/dL). Changes in T levels and the dose of TRT required to achieve serum T level within (300 - 1050 ng/dL) were collected.

Results: At baseline, 74 and 80 subjects were in the T<230 and T 230 ng/dL groups respectively (one subject was removed from the analysis due to protocol violation of using TRT prior to baseline). At day 15, patients whose T levels at baseline were <230ng/dL had slightly lower serum T levels (413 vs. 463, p=0.09). Similar results were seen on day 60 (470 vs 486, p=0.66) and day 120 (447 vs. 502, p=0.04). However, a similar proportion of patients in each group reached the threshold of 300ng/dL. Among patients who had a Day 45 visit, numerically higher proportion of patients in the <230 group required dose escalation (22% vs. 17%) based on the Day 15 T level; however, the difference is not statistically significant (p=0.52, based on the Fisher’s exact test).

Conclusions: While baseline T levels may affect the final T concentration, a similar proportion of patients was within the normal range and reach the therapeutic goal. Patients, especially those with very low levels at baseline, may benefit from close monitoring of testosterone levels and appropriate dose adjustment.

 

[Michael Scally MD]

Q: Is the “Cascade Effect” a problem in endocrinology?

A: Yes, examples include discovery of endocrine incidentalomas on head and body scans (MRI/CT).

 

[Michael Scally MD]

Reversible Idiopathic Hypogonadotropic Hypogonadism: Clinical and Genetic Characteristics
http://edrv.endojournals.org/cgi/content/meeting_abstract/34/03_MeetingAbstracts/SAT-163 (Reversible Idiopathic Hypogonadotropic Hypogonadism: Clinical and Genetic Characteristics -- Sidhoum et al. 34 (3): SAT-163 -- Endocrine Reviews)

Idiopathic hypogonadotropic hypogonadism (IHH) is caused by defective synthesis, secretion, or action of GnRH. Patients with IHH have low sex steroids and low or inappropriately normal gonadotropins in adulthood and are traditionally thought to require lifelong therapy. However, some individuals undergo spontaneous improvement of their reproductive function in the absence of therapy, a phenomenon termed "reversal".

Charts of 389 IHH patients with detailed medical follow-up and documentation were reviewed. Reversal was defined as 1 of the following: 1) fertility without GnRH/gonadotropins, 2) LH pulse frequency and amplitude within the normal range, 3) serum testosterone 250 ng/dL off therapy, 4) testicular volume 4 ml and >2 ml of growth without use of GnRH/gonadotropins, and 5) spontaneous menstrual cycling. Relapse was defined as once again developing hypogonadal sex steroid levels off therapy (testosterone <100 ng/dl in men, estradiol <20 pg/ml in women).

Of 389 patients with IHH, 13% (45 men, 5 women) met criteria for reversal. Reversal was first noted at a mean age of 27 y (range 19-55 y) and in individuals with both no pubertal development (testes <4 ml, microphallus, cryptorchidism, apulsatile LH secretion) and partial pubertal development. Surprisingly, 30% (n=15) had Kallmann syndrome (IHH + anosmia). One anosmic patient demonstrated absent olfactory bulbs on MRI (structures important for proper GnRH neuronal migration). Among reversal probands, 16% (6/38) carried deleterious mutations in the neurokinin B signaling pathway (TAC3 and TACR3) compared to 5% (43/826) of IHH patients in general (p=0.02). Four men did not sustain their reversal and reverted back to their hypogonadotropic state.

Four key findings emerged from our examination of patients with reversal of IHH:

1) reversal can occur across a broad range of ages and disease severity,
2) GnRH neurons are not strictly dependent on an intact olfactory system to reach their target destinations in the hypothalamus, challenging the prevailing dogma of over 20 years,
3) mutations that disrupt the neurokinin B signaling pathway continue to emerge as a genetic signature for reversal, suggesting that they may display reduced pathogenicity over time, and
4) reversal is not always sustained.

All individuals with IHH should periodically undergo brief therapy discontinuation to be screened for reversal and should be counseled about the possibility of reversal and relapse.

 

[Michael Scally MD]

My Balls are Small - A Steroid Love Song
[In other words Anabolic-Steroid Induced Hypogonadism (AIH) prevention/elimination is important.]
[ame=http://www.youtube.com/watch?v=JU7JS-sp6CY]My Balls are Small - A Steroid Love Song - By Mark Lim - YouTube[/ame]

 

[Michael Scally MD]

I was sent an email yesterday asking whether Vt. E would aid/help PCT? They sent along a link to an article by A. Roberts. Do yourself a favor, except for maybe gossip do not read any of the crap by this guy.

And, NO Vit. E will not help PCT. If you are Vit. E deficient, you have some serious diet problems. Also, do not supplement with Vit. E.

Also, FYI.

Conclusion Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.

Klein EA, Thompson IM, Tangen CM, et al. Vitamin E and the Risk of Prostate Cancer. JAMA: The Journal of the American Medical Association 2011;306(14):1549-56. http://jama.ama-assn.org/content/306/14/1549.abstract

 

[tendency]

some really great info in this thread doc.

how's the book coming?

 

[Michael Scally MD]

Kovac JR, Scovell J, Ramasamy R, et al. Men regret anabolic steroid use due to a lack of comprehension regarding the consequences on future fertility. Andrologia. http://onlinelibrary.wiley.com/doi/10.1111/and.12340/abstract

We examined whether men with anabolic-steroid-induced hypogonadism (ASIH) seeking testosterone supplementation therapy (TST) regretted their decision to use anabolic-androgenic steroids (AAS) and what their reasons were for this regret.

An anonymous, prospective survey was distributed to 382 men seeking follow-up treatment for hypogonadism. Prior AAS use was confirmed by self-report, and men were categorised based upon whether they regretted (R) or did not regret (NR) their use of AAS.

The average patient age was 40 ± 0.9 years (n = 79) and 15.2% expressed regret over AAS use. No demographic differences were identified between those who regretted AAS use (n = 12) and those who did not (n = 67).

Regret was not related to ASIH diagnosis or to AAS-related side effects like increased aggression, mood disorders, erectile dysfunction, acne, fluid retention or dyslipidemia.

Those who regretted AAS use were significantly more likely to have not comprehended the negative impact on future fertility (P < 0.030). Actual fertility issues were comparable in men who regretted AAS use (16.7%) and those who did not (13%).

A total of 15.2% of men regretted using AAS. A lack of awareness regarding the negative long-term effects on fertility was the primary factor related to regret of AAS use in men with ASIH.

 

[Northern Nutrition]

Gotta love the "hCG Diet". If you drop your calories down to 500 you could eat vitamin c (or anything else for that matter) and call it the Vitamin C Diet..lol. What a joke..

 

[Michael Scally MD]

[FWIW: I am a coauthor on this paper. Dr. Quinton, a well-respected endo, asked me to participate. I will continue to help raise awareness on ASIH. And, deal with the idiots at TMB.]

Karavolos S, Reynolds M, Panagiotopoulou N, McEleny K, Scally M, Quinton R. Male central hypogonadism secondary to exogenous androgen: a review of the drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects. Clinical Endocrinology. http://onlinelibrary.wiley.com/doi/10.1111/cen.12641/abstract

Androgen- or anabolic steroid-induced hypogonadism (ASIH) is no longer confined to professional athletes; its prevalence among young men and teenagers using androgens and/or anabolic steroids (AAS) is rising fast, and those affected can experience significant symptoms.

Clinicians are increasingly encountering demanding, well-informed men affected by ASIH, yet lacking authoritative information on the subject may struggle to project a credible message.

In this article we overview the methods and drugs that men use in an attempt to counteract ASIH (with a view to either preventing its onset, or reversing it once it has developed), and summarise the scientific evidence underpinning these.

The main channel for obtaining these drugs is the Internet, where they can be readily sourced without a valid prescription. An Internet search using relevant terms revealed a huge number of websites providing advice on how to buy and use products to counteract ASIH.

Drugs arising repeatedly in our search included human chorionic gonadotrophin (hCG), selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The quality and accuracy of the online information was variable, but review of medical literature also highlighted a lack of scientific data to guide clinical practice.

It is important for clinicians to be aware of the AAS user's self-treatment strategies with regards to ASIH side-effect mitigation. By ensuring that they are well-informed, clinicians are more likely to retain the credibility and trust of AAS-users, who will in turn likely be more open to engage with appropriate management.

 

[Millard]

Congratulations on the publication! And thank you @Michael Scally MD for all your continued efforts at promoting awareness of ASIH (and especially ASIH treatment)!

 

[Michael Scally MD]

27 Cites - Not much, but more than I would have thought. The article I wrote regarding ASIH has been cited 27 times. WTH! Maybe, they will get around to the treatments I published someday. https://www.researchgate.net/profile/Michael_Scally/stats/citations