Hypogonadotropic Hypogonadism
Pulsatile secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus is required for both the initiation and maintenance of the reproductive axis in the human. Pulsatile GnRH stimulates the biosynthesis of luteinizing hormone (LH) and follicle stimulating hormone (FSH) that in turn initiates endogenous testosterone production and spermatogenesis as well as systemic testosterone secretion and virilization. Failure of this episodic GnRH secretion or disruption of gonadotropin secretion results in the clinical syndrome of hypogonadotropic hypogonadism (HH).
The usage of anabolic androgenic steroids (AAS) may result in a functional form of HH known as Secondary Acquired Hypogonadotropic Hypogonadism and is diagnosed in the setting of a low testosterone level and sperm count in association with low or inappropriately normal serum LH and FSH concentrations.
In order to avoid any unnecessary confusion, it is important to understand what the actions of Gonadatropin therapy and Selective Estrogen Receptor Modulators are as well as how they differ from each other and more specifically, during post cycle recovery (PCT).
Gonadotropin Therapy
There is nothing more effective than Human Chorionic Gonadotropin (HCG). The action of HCG is identical to that of pituitary LH. This takes place independently and is not affected by exogenous hormones and/or preexisting HPTA suppression. Therefore, it directly stimulates a dramatic increase in endogenous testosterone production, spermatogenesis and testicular volume. The primary goal during the first few weeks of PCT is to quickly restore testicular volume and function. Also, the dramatic increase in testosterone production is necessary to avoid and/or minimize the unfavorable “crash” effect. In the majority of individuals with larger testes at baseline, HCG alone is sufficient in restoring endogenous testosterone production as well at the induction of spermatogenesis which is most likely a result of residual FSH secretion. Once there is a plateau in the response to HCG, treatment with an FSH preparation such as human menopausal gonadotropin (HMG) or recombinant follicle stimulating hormone (rFSH) should be added in combination to HCG.
*The addition of an FSH preparation is rarely required and is best suited for severe cases of HH. FSH preparations are not readily available to most individuals. Therefore, there is no need to go into details with respect to its application at this time.
HCG is administered by subcutaneous (SC) or intramuscular (IM) injection. The average (3ml 22-25G x �-1½�) syringe is adequate for IM injections but insulin syringes (½-1ml 28-30G x ½-1�) are recommended for SC injections. In regards to effectiveness, there should be no discernable difference between either of the techniques. The individual should opt for the most comfortable and/or convenient form of administration.
The following is a description of the available preparations by Serono:
HCG ampoules are supplied in 500, 1,000, 2,000, 5,000 and 10,000 IU preparations accompanied by 1 ml of sterile dilluent. It should be stored at a controlled room temperature (15-30 degrees C or 59-86 degrees F) and should be used immediately after reconstitution.
HCG multidose vials are supplied in 2,000, 5,000 and 10,000 IU preparations accompanied by 10 ml of bacteriostatic water. It should be stored at a controlled room temperature (15-30 degrees C or 59-86 degrees F), refrigerated (2-8 degrees C or 36-46 degrees F) after reconstitution and used within 30 days.
Other manufacturers are available and preparations may vary.
The terms international units (IUs) can occasionally cause confusion when reconstituting and measuring HCG. The actual process is quite elementary and the concentration per ml (cc) is dependant on the concentration of the lyophilized powder and the volume of dilluent used for reconstitution. For example, if you dilute 5,000 IUs HCG with 5ml (cc) solvent, the end result is 1,000 IUs per ml (cc). Divide the same 5,000 IUs with 10 ml (cc) and the end result is 500 IUs per ml (cc).
*Bacteriostatic water should always be utilized during reconstitution when long term (30 day) storage and multi dose administration are required.
Selective Estrogen Receptor Modulators
Selective estrogen receptor modulators (SERMs) such as Clomiphine (Clomid) and Tamoxifen (Nolvadex) increase pituitary LH secretion in secondary manner by blocking estrogen negative feedback on the HPTA. On average, this is not strong enough by itself to counteract the severe imbalance of the androgen:estrogen ratio that is encountered post cycle, especially in the presence of testicular atrophy. Therefore, SERMs are used during PCT primarily as an anti estrogen and to continue the stimulation of pituitary LH after HCG has been discontinued.
Nolvadex is widely available in 10 mg or 20 mg tablet preparations and Clomid is available in 50 mg tablet preparations.
Before Beginning PCT
It is highly recommended to establish baseline blood values before beginning a cycle. The same principle applies to establishing post cycle blood values, which are necessary for evaluating recovery. Post cycle blood work should be obtained approximately 4 weeks after the cessation of PCT in order to determine accurate readings. Additional blood work should be performed when applicable and/or required.
The following are Fasting blood values:
Hormone
1. Cortisol, Total
2. Estradiol, Extraction
3. Prolactin
4. LH
5. FSH
6. T3, Free
7. T4, Free
8. TSH
9. Testosterone, Total, Free and Weakly Bound
10. Hemoglobin A1C
11. Fasting Insulin
12. Somatomedian C (optional)
Cardiovascular
13. CBC
14. Comprehensive Metabolic Panel
15. Lipid Panel
Other
16. GGT Important Liver Value not included in Comp Metabolic Panel
When to begin PCT
On average, begin PCT approximately 5-10 days after your last injection regardless of longer acting esters. Begin PCT 1-3 days after your last injection and/or intake when using short acting esters.
Keep in mind, pituitary LH secretion automatically increases as the hormones diminish from your system. The elevated androgen levels are from an exogenous source and your endogenous production is suppressed. Therefore, waiting for the exogenous androgens to completely clear from your system, ultimately results in lower total concentrations of androgens in your system when beginning PCT. This leads to an unfavorable andgrogen:estrogen ratio and the well known “crash� effect.
*As previously mentioned, the actions of HCG take place independently and is not affected by exogenous hormones and/or preexisting HPTA suppression. There are no contradictions with respect to the effectiveness of HCG usage while exogenous hormones are present in your system.
PCT Protocol(s)
1.) 1,000 IUs HCG 3x/wk (mon/wed/fri) in combination with 20 mgs Nolvadex ED for the first 3 weeks. After, discontinue HCG and continue with 20 mgs Nolvadex ED for an additional 3 weeks.
2.) 1,000 IUs HCG 3x/wk (mon/wed/fri) in combination with 20 mgs Nolvadex ED and 50 mgs Clomid ED for the first 3 weeks. After, discontinue HCG and continue with 20 mgs Nolvadex ED and 50 mgs Clomid ED for an additional 3 weeks.
3.) 1,500 IUs HCG 3x/wk (mon/wed/fri) in combination with 20 mgs Nolvadex ED for the first 3 weeks. After, discontinue HCG and continue 20 mgs Nolvadex ED for an additional 3 weeks.
4.) 1,500 IUs HCG 3x/wk (mon/wed/fri) in combination with 100 mgs Clomid ED and 20 mgs Nolvadex ED for the first 3 weeks. After, discontinue HCG and continue with 50 mgs Clomid ED and 20 mgs Nolvadex ED for an additional 3 weeks.
Option one can be considered as a standard PCT protocol. This should apply to all basic cycles. Option 2 is generally the same as option one except for the addition of Clomid which is added as a supporting recovery aid. Option three and four incorporate a higher HCG dosage and have a relationship similar to options one and two in the sense that Clomid is incorporated in the latter as a supporting recovery aid.
*The majority of my experience is with intermediate to advanced athletes whom have completed multiple cycles with higher dosages. Therefore, based upon previous blood work results and considering the common or convenient preparations available, we have established that 1,500 IUs 3x/wk (mon/wed/fri) to be the optimal HCG dosage to begin with. The Nolvadex dosage remains unchanged however Clomid is utilized throughout the entire PCT at 100 mgs ED during the first 3 weeks and 50 mgs ED for the last 3 weeks.
HCG During Cycle
HCG in combination with Nolvadex can and should be used during prolonged (12+/wks) and high dosage (1,000+mgs/wk) cycles. In this case, 500-1,000 IUs HCG ED in combination with 20 mgs Nolvadex ED for 7-10 days consecutively is administered mid cycle or intermittently (every 6-8 weeks) during the cycle.
Maintaining testicular volume during cycle does in fact improve recovery when compared to atrophied testes when beginning PCT. This solution addresses both testicular atrophy and prevention of Leydig cell desensitization (discussed next) associated with HCG usage.
Leydig Cell Desensitization
Leydig cell desensitization does in fact occur to some degree with prolonged or high dose HCG usage. Using it continuously during a cycle could possibly cause the LH receptor to desensitize which in turn would ultimately render the PCT to be either less effective or possibly useless. This seems counterproductive. HCG will not be needed on cycles where the proper ancillaries are used and where the dosages/durations are realistic.
The previous summary was a general statement. The reality and good news is that Leydig cell desensitization due to HCG usage is blocked and/or minimized by Nolvadex. This occurs by suppressing HCG’s ability to inhibit the conversion of 17 alpha hydroxyprogesterone to testosterone.
Additional Factors That Influence Recovery
Factors that may complicate and/or delay recovery are elevated levels of estrogen and prolactin. Both of these hormones, when elevated, exert negative feedback on the HPTA. Estrogen and its side effects can be controlled by using an aromatase inhibitor such as Aromasin, Femara and Arimidex during cycles including aromatizing AAS. Prolactin and its side effects can be controlled by using an anti Prolactin such as Cabergoline (Dostinex) or Bromocriptine (Parodel) during cycles containing nandrolones. If these measures have not been addressed during the cycle, they will more than likely need to be addressed during PCT. In this scenario, the objective is to lower these hormones to acceptable levels in order to avoid the complications and/or delay in recovery. Blood work is imperative in evaluating the effectiveness of therapy. This will provide a clear and concise answer in regards to the adjustment of dosages and continuation of medication if necessary.
*There are numerous studies which support and refute the association of nandrolones and prolactin. However, based on first hand experience and blood work results, there are far more individuals today whom can testify that the usage of nandrolones can attribute to an increase in prolactin concentrations. In addition, many individuals have reported elevated prolactin levels during cycles which do not contain nandrolones. The common factor within these cases is supraphysiological levels of estrogen. Estrogens act directly at the pituitary level by causing the stimulation of lactotrophs which in turn enhances prolactin secretion. This is another reason why estrogen management in the form of an aromatase inhibitor should be included with cycles containing aromatizing AAS. Although not absolutely necessary and considering the necessary restoration of physiological estrogen values, there is sufficient evidence which suggests that aromatase inhibitors can improve and increase recovery rates.
Unsuccessful PCT
In some cases the aforementioned post cycle therapy protocols as well as those which are not mentioned may be unsuccessful in the restoration of homeostasis. This should not warrant immediate concern. Many endocrinologists have concluded that the only form of treatment in this particular scenario is hormone replacement therapy (HRT).
This is far from the truth. The reason many endocrinologists have come to this conclusion is due to the fact that very few of them have the experience treating severe forms of secondary acquired hypogonadotropic hypogonadism. They are unfamiliar with proper protocols which include high dosage HCG administration and additional gonadotropin preparations such as HMG or rFSH. This complication puts the patient at risk for potential and unknown side effects in the eyes of the doctor. Therefore, HRT is a reasonable solution since it will quickly alleviate the majority of the uncomfortable symptoms that the patient is experiencing.
Aside from disappointing blood work results which illustrate the typical signs of an unsuccessful recovery, the key physical indicator that the treatment is unsuccessful is testicular atrophy. In this case, HCG is continued with the necessary adjustments in dosage and frequency until an increase in testicular volume has been achieved. There is no one size fits all protocol since every case varies and deserves an individualized approach. Subsequent changes will be based upon the individual’s response to each particular stage. All the variable factors involved during the recovery process need to be considered. It’s far from accurate to reach the conclusion that HRT is needed if one specific recovery protocol is not successful.
Ongoing Argument(s)
Hypothetically speaking, if testicular function and volume have been maintained during cycle with HCG, SERMs are then utilized to counteract the imbalance in the androgen:estrogen ratio encountered post cycle as the exogenous androgens diminish. This results in the prevention of estrogenic side effects while increasing pituitary LH secretion which in turn increases testosterone production.
There is nothing wrong with using a commonly referred to protocol which recommends 250-500 IUs HCG 1-2x/wk to be incorporated throughout the cycle. However, a significant cause for concern in regards to this protocol relates to the cessation of HCG once the cycle has completed and from that point on, the only substances used during PCT are SERMs which consist of Nolvadex and/or Clomid. Realistically, there is absolutely no guarantee that this formula prevents testicular atrophy to the extent where the overall volume and function of the testes are in an optimal state. Unfortunately, a large majority of individuals do not realize or are not aware that Leydig cell desensitization does in fact occur with prolonged or high dosage HCG usage. Therefore, users which follow this protocol whom do not incorporate Nolvadex or an aromatase inhibitor are now susceptible to Leydig cell desensitization which may render HCG usage post cycle ineffective when and if needed.
During conservative cycles, there is substantial evidence which exists that supports the effectiveness of the HCG during cycle and SERMs only post cycle protocol, especially when proper estrogen and prolactin management has been incorporated. However, this conclusion is much more difficult to achieve on heavy or prolonged cycles. Testicular volume should be maintained to an acceptable extent but that does not necessarily result in an improved recovery as severe HTPA suppression still exists which is not immediately repairable through the usage of SERMs.
The most common argument here when incorporating HCG during PCT is that HCG itself is suppressive. This is true and one particular way this occurs is though the constant binding of HCG which disrupts the endogenous pulsatile secretion of LH. A recent study which included the usage of 250 mcgs Ovidrel (rHCG) 2x/wk for 12 weeks demonstrated that the patients resumed normal HPTA function within four weeks upon cessation, without the usage of SERMs. What’s even more interesting is that 250 mcgs rHCG is the equivalent of approximately 5,000 IUs uHCG. Therefore, putting things into perspective, a few additional weeks of suppression is nothing to be overly concerned about compared to and considering the 12 weeks of suppression incurred during the average cycle. The usage of HCG during PCT is a minimally intrusive variable where the benefits clearly exceed the associated costs.
Conclusion
PCT should begin after the last injection and/or AAS intake. More specifically, a relative guideline to begin PCT is within 5-10 days when using long acting esters or 1-3 days when using short acting esters. This PCT protocol should consist of 1,000-1,500 IUs HCG 3x/wk (mod/wed/fri) in combination with 20 mgs Nolvadex ED and, if necessary, 50-100 mgs Clomid ED. The mid/intermittent cycle protocol of 500-1,000 IUs HCG and 20 mgs Nolvadex ED for 7 days consecutively can and should be utilized when necessary during prolonged (12+/wks) or heavy dosage (1,000+mgs/wk) cycles. In addition, blood work should be performed before beginning a cycle and after completing a cycle in order to establish baseline values and evaluate recovery, respectively.
If recovery is unsuccessful, HCG is continued with an adjustment in dosage and frequency as necessary until the increase in testicular volume and function have been achieved which is unlike the more typical, yet incorrect belief that HCG is only to be used for a short period of time. Once there is a plateau in the response to HCG, treatment with an FSH preparation such as human menopausal gonadotropin (HMG) or recombinant follicle stimulating hormone (rFSH) should be added at a starting dose of 75-150 IUs on alternate days. This continual usage is not necessary and avoidable in most cases by utilizing the mid/intermittent protocol previously mentioned, but it is much more common and less avoidable with long term (1+/yr) users, whom have not taken the suggested preventive measures, and/or improper recovery from previous cycles regardless of which protocol is chosen.
With the usage of HCG post cycle, your androgens are elevated but well below that of supraphysiological concentrations from exogenous hormones. In addition, a noteworthy difference is that the effect is through a direct stimulation of testicular production compared to the secondary nature of SERMs in conjunction in the presence of testis that are not guaranteed to be in an optimal functioning state. Upon completion, blood work will display significantly higher levels of LH, FSH and testosterone in this environment which includes HCG and SERMs during PCT versus HCG during cycle and SERMs only during PCT. This ultimately results in a more comfortable as well as tolerable recovery both physically and psychologically. In conclusion, HCG should always be included during PCT in combination with SERMs regardless of what protocol has been utilized during cycle to prevent testicular atrophy, in order to achieve an optimal recovery.