Getting Off Testosterone or Anabolics? You May Want to Read this HPTA protocol

Nelson Vergel · Dec 1, 2014

PCT post TRT....

Nelson Vergel · Jul 29, 2015

From an interview I did with Dr Scally:

NV: Can you expand about resetting the HPGA?

The word resetting is a misnomer, although recent studies published in the New England Journal of Medicine do indicate this possible. In 2007, the NEJM reports on the resetting of the HPTA after TRT for adult onset idiopathic hypogonadism. This is the first report demonstrating HPTA plasticity in adulthood. The term I prefer is HPTA functionality and restoration.

AAS, including testosterone, licit and illicit, administration induce a state of hypogonadism that continues after their cessation. All compounds classified as androgens or anabolic steroids cause a negative feedback inhibition of the hypothalamic pituitary testicular axis, suppress endogenous gonadotropin secretion, and as a consequence serum testosterone.

The symptoms of AIH are identical to classical hypogonadism. This problem prevents many of discontinuing testosterone or anabolic steroids. As we have said, there are many reasons for stopping testosterone, including polycythemia, gynecomastia, and other issue as compliance, affordability, and changing life style.

The accepted standard of care within the medical community for anabolic steroid induced hypogonadism is to do nothing with the expectation the individual will return to normal unassisted. But the literature shows this not to be the case.

AIH is critical towards any future planned use of AAS or similar compound to effect positive changes in muscle mass and muscle strength as well as an understanding for what has been termed anabolic steroid dependency. The further understanding and treatments that mitigate or prevent AIH could contribute to androgen therapies for wasting associated diseases and stopping nonprescription AAS use.

NV: What is used for this resetting of the hormonal axis?

MS: A combination of three drugs. The individual use of hCG, clomiphene citrate, and tamoxifen are well-known, well-accepted, and well-tested standards of care treatments in peer-reviewed medical literature for the diagnostic testing for underlying pathology of hypogonadism. The HPTA protocol uses the medications human chorionic gonadotropin -hCG, clomiphene citrate, and tamoxifen.

The first phase of the HPTA protocol examines the functionality of the testicles by the direct action of hCG. hCG raises sex hormone levels directly through the stimulation of testis and secondarily decreases the production and level of the gonadotropin LH. The increase in serum testosterone with the hCG stimulation is useful in determining whether any primary testicular dysfunction is present.

This initial value is a measure of the ability of the testicles to respond to stimulation from the hCG. Demonstration of HPTA functionality is by an adequate response of the testicles to raise the serum level of T well into the normal range. If this is observed the hCG is discontinued. The failure of the testes to respond to an hCG challenge is indicative of primary testicular failure. In the simplest terms, the first half of the protocol is determine testicular production and reserve by direct stimulation with hCG. If one is unable to obtain adequate (normal) levels successfully to the first half there is little cause or reason to proceed to the second half.

The second phase of the HPTA protocol, clomiphene and tamoxifen, examines the ability of the hypothalamo-pituitary to respond to stimulation by producing LH levels within the normal reference range. The clomiphene citrate challenge differentiates secondary hypogonadism. Clomiphene is an antiestrogen, which decreases the estrogen effect in the body. It has a dual effect by stimulating the hypothalamic pituitary area and it has an antiestrogenic effect, so that it decreases the effect of estrogen in the body. Tamoxifen is more of a strict antiestrogen, it decreases the effect of estrogen in the body, and potentiates the action of clomiphene. Tamoxifen and clomiphene citrate compete with estrogen for estrogen receptor binding sites, thus eliminating excess estrogen circulation at the level of the hypothalamus and pituitary, allowing gonadotropin production to resume.

Administration produces an elevation of LH and secondarily gonadal sex hormones. The administration of clomiphene leads to an appropriate rise in the levels of LH, suggesting that the negative feedback control on the hypothalamus is intact and that the storage and release of gonadotropins by the pituitary is normal. If there was a successful stimulation of testicular T levels by hCG, but an inadequate or no response in LH production, then the patient has hypogonadotropic, secondary, hypogonadism.

In the simplest terms, the second half of the protocol is to determine hypothalamo-pituitary production and reserve with clomiphene and tamoxifen. The physiological type of hypogonadism—hypogonadotropic or secondary—is characterized by abnormal low or low normal gonadotropin (LH) production in response to clomiphene citrate and tamoxifen. In the functional type of hypogonadism, the ability to stimulate the HPTA to produce LH and T levels within the normal reference range occurs.

There is a dearth of good studies in anabolic steroids, both while you're taking them and after you stop them, I think this is going to be something that we're going to need to look at in the future. In fact, we are going to plan on looking at it in our proposed clinical studies that we have with our company for the prevention of anabolic steroid-induced hypogonadism.

Nelson Vergel · Jan 4, 2017

Post PCT Panel

ABOUT THIS TEST

This panel is designed to measure the health and recovery of the Hypothalamic-Pituitary-Testicular Axis (HPTA) after attempting to normalize it spontaneously or with the use of Post-Cycle Therapy (PCT) with hCG, clomiphene and/or tamoxifen. PCT is prescribed by some physicians for men who stop testosterone replacement therapy (TRT) or Anabolic-Androgenic Steroids (AAS).

Testosterone replacement therapy and anabolic steroids can lead to HPTA (Hypothalamic-Pituitary-Testicular Axis- shown in figure below) dysfunction. Supplemental testosterone can inhibit the release of the body's own testosterone production through negative feedback inhibition on LH levels. This feedback inhibition also results in suppression of FSH levels, leading to suppression of sperm production (spermatogenesis).

It is suggested that this panel be done no sooner than 4 weeks after PCT cessation and in a fasting state (morning time)

Tests included:

- Sensitive Estradiol (E2) by Liquid Chromatography/Mass Spectrometry (LC/MS assay used to more accurately measure estradiol in men)

- Total and Free Testosterone [ Free T: direct analog/radioimmunoassay (RIA); Total T: electrochemiluminescence immunoassay (ECLIA) ]

- Luteinizing Hormone (LH) (Responsible for activating Leydig testicular cells to produce your own testosterone). This hormone is shut down by testosterone replacement or AAS.

- Follicle Stimulating Hormone (FSH) (Responsible for activating Sertoli testicular cells to produce sperm). This hormone is shut down by testosterone replacement or AAS.

- CBC - Complete Blood Count (Includes hematocrit)

- CMP - Comprehensive Metabolic Panel (Includes liver and kidney function, glucose and electrolytes)

BUY PANEL HERE

Nelson Vergel · Dec 26, 2018

Is the reversibility of Anabolic steroid-induced hypogonadism achievable? A systematic review

The abuse of anabolic androgenic steroids (AAS) is a growing problem that is widely spread among teenagers and unprofessional gym attendees that use these substances usually for cosmetic purposes. The prevalence of AAS use worldwide is estimated to be 6.4 % in men and around 60,000 users are reported every year in the UK. AAS abuse is associated with many health complications. In this systematic review, the impact of these substances on male gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH) is critically investigated and reviewed. A systematic review was conducted from 03/10/2016 to15/03/2017 using PubMed databases to investigate the effects of exogenous anabolic steroids on the reproductive organs. Relevant and primary references were screened for supporting evidence and background information about the subject. Main outcomes included were: full clinical examination of AAS abusers, which were men of reproductive age. All the animal studies were excluded. Full clinical examination and assessment consisted of blood tests to measure gonadotropins (LH and FSH) and testosterone levels, as well as semen analysis including sperm count, concentration and morphology. In total 30 papers including primary references passed the inclusion criteria and were assigned in this systematic review. All papers reported successful reversibility of the gonads after steroids cessation and some pregnancies were achieved with and without gonadotropins treatment. However, the recovery phase of gonadotropins was highly dependent on the number of substances administrated and the duration of abuse, as some patients reported prolonged infertility problems after years of cessation. No permanent suppression of gonadotropins was reported. It was concluded that the reversibility of suppressed gonadotropins is highly achievable especially when treated with human chronic gonadotropin (HCG) and human menopausal gonadotropins (hMG) even with the severest cases. Therefore male infertility issues reported by AAS abusers should always be addressed and treated properly.

Source

Nelson Vergel · Dec 26, 2018

Low Testosterone After Anabolic Steroids: A Review of Online Site PCT Protocols

Nelson Vergel · Dec 26, 2018

Trying to Regain Natural Testosterone After High T Dose Use

Nelson Vergel · Dec 26, 2018

HPTA restart need help

Nelson Vergel · Jan 30, 2019

Clomid to Reset Hormonal Axis After Anabolic Steroids

Nelson Vergel · Jun 18, 2019

What happens after 14 weeks of weekly injections of 100 mg, 250 mg and 500 mg of testosterone cypionate when patients stop? No PCT. Young and healthy males.

Nice graphs at the end of the paper (attached). Intensive sampling (finally!)

Testosterone returned to baseline at week 23 (last injection at week 14). So, it took 9 weeks for their HPTA to recover, which I find it to be fast for a 500 mg/week dose exposure for 14 weeks. Subjects were healthy and young, so that may have been the reason.

Population Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Depot Testosterone Cypionate

Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
Long-term excessive dosing of anabolic steroids can lead to serious health risks. One of the most significant physiologic changes induced by the use of testosterone esters is a dose-dependent impairment of normal testicular androgen secretion and spermatogenesis.

WHAT QUESTION DID THIS STUDY ADDRESS?
This study characterizes and quantifies changes in testosterone and luteinizing hormone concentration, and spermatogenesis following long-term testosterone cypionate administration.

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
The study developed a PK-PD model based on a randomized three-arm (100mg, 250mg, 500 mg/week) clinical trial which quantified the relationship between testosterone exposure after exogenous administration and suppression of LH and spermatogenesis. Model results showed that the suppression of endogenous testosterone secretion, LH synthesis, and spermatogenesis was more severe and of greater duration in 250mg and 500mg dose groups.

HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?
This PK/PD model provides a framework to quantify and predict the change in LH and spermatogenesis after exogenous testosterone administration. The average concentration of total testosterone in the past 18 weeks was found to have the strongest association with suppression of spermatogenesis.

Bi Y, Perry PJ, Ellerby M, Murry DJ. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Depot Testosterone Cypionate in Healthy Male Subjects. CPT: Pharmacometrics & Systems Pharmacology.

A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate. Thirty-one healthy males were randomized into a dose group of 100, 250 or 500mg/wk and received 14 weekly injections of TC.

[The endogenous testosterone secretion rate returned to baseline at approximately week 23 in all three dose groups.]

Nelson Vergel · Jul 10, 2019

Hormonal recovery after anabolic steroid cycle lasts longer than 4 months

Four months after an anabolic steroid cycle, the production of hormones such as LH and FSH, which stimulate the testes to produce testosterone, will be recovered - but this does not apply to the production of testosterone. This is apparent from a meta-analysis that Greek endocrinologists at the University of Ioannina published in Sports Medicine.

Hormonal recovery after anabolic steroid cycle lasts longer than 4 months

Nelson Vergel · Sep 12, 2019

How to Improve Sperm Quality, LH, FSH and Testosterone in Infertile Men

Nelson Vergel · Aug 28, 2020

Coming off TRT- Defy HPTA Reset Protocol

I am curious if anyone knows what sort of HPTA protocol Defy Medical offers. I'm considering coming off TRT. I am currently a Defy patient and they have managed my protocol very well, but I just don't feel a huge benefit from TRT a year later even with Test levels going from 350 to...

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HPTA recovery log

Has anyone ever recovered from testosterone abuse or long term testosterone therapy (can it cause permanent damage)?? If so, I would like to hear your story and how long it took you to recover your HPTA... There may be a topic out there already, but I figured I ask again. I know there are a lot...

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HPTA restart need help

Hi guys My name is Garðar and I’m from Iceland, i need advice on dr scally’s protocol. The post i was reading your comments has been locked I hope it’s ok that I post here. I’ve twice done steroid cycles and I’m prettt extreme when it comes to evertthing lol(addict but sober now 2 years) My...

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Getting Off TRT: Replace Clomid with Enclomiphene in HPTA Reset Protocol?

What are peoples thoughts about replacing Clomid with Enclomiphene in this reset protocol? Protocol has just been copied from one of Nelsons posts in 2016. Defy Medical HPTA Reset Protocol by Jasen Bruce During the previous years large surge in testosterone prescriptions and TRT clinics there...

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Need help HPTA restart HCG protocol

Hi all and Nelson I have stopped TRT cos of my low shbg and high E2 thus TRT really didn't work for me. My Endocrinologist doesn't believe in AI or SERM treatments so I had no choice but to go TRT route. Now obviously my HPTA shutdown as my LH and Fsh are 1.0 and 0.8 last i checked...

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hpta

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HPTA Restart in Young Men After Anabolic Steroids

Anabolic steroids and testosterone shut down the body's Hypothalamic-Pituitary-Testicular Axis (HPTA) while people use them and for a few weeks after cessation of these compounds. However, some men's testosterone production does not recover back to baseline values. These men have...

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Forum list

The Most Respected Testosterone TRT Men's Health Forum Since 2013

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Dr. Scally's most current Restart Protocol?

Hey guys, Is this Dr. Scallys most current Restart Protocol?: Phase 1: HCG 2500iu EOD for 16 days Phase 2: Clomid 50mg twice daily for 30 days Tamoxifen 20mg daily for 30 days Phase 3: Tamoxifen 20mg daily for 15 more days

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TRT Reset protocol questions

Hi all, i've been on TRT for about a year. Took a break 6 months ago for about 6 weeks and intend to do so again starting now. I'd like your advice on reset protocol. I've been taking 50-75 test e every 3 days together with hcg and nolvadex (tiny amounts). My question is, as...

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Nelson Vergel · Jun 1, 2026

Thread 'How to Stop Testosterone Safely and Possibly Reset Your Hormonal Axis'

Sep 17, 2013

From the book: Testosterone: A Man's Guide (click here)

Some men need to stop using testosterone or other androgens because side effects are a problem (e.g. low sperm count interferes with their goal to have children). Most physicians advise the patient to just stop testosterone without thinking about the possible consequences of the hypogonadal state after treatment cessation. Will the patient be worse off than when he started?