The use of 17-OH Progesterone to predict response to HCG

[Youthful55guy]

I found this interesting discussion on the use of a 17 - OH Progesterone test to estimate an individuals potential response to HCG. I've not done the test ($79 at DiscountLabs.com), and don't feel the need to give that I could care less about my sperm production at my age. However, some guys here might find it useful. They cite an article that I've not yet read which indicates that an HCG dose closer to 1750 IU per week (500 IU E2D) normalizes ITT values in guys undergoing TRT. An earlier 2005 article coauthored by this same researcher (which I've discussed in other threads) indicated the optimum dose was closer to 1000 IU per week. Perhaps this is an update to that earlier research.

This test uses liquid chromatography/mass spectrometry (LC/MS) the most accurate method for hormone testing.

The use of testosterone replacement therapy (TRT) increases blood levels of testosterone but, surprisingly, it decreases the level of testosterone inside the testicles (Intratesticular testosterone or ITT). ITT is key for proper sperm production. This ITT decrease is due to the LH and FSH shut down that occurs with TRT. This shut down decreases ITT and sperm production in men on TRT. These two gonadotropins are required to maintain healthy levels of ITT and, thus, sperm production. Some men on TRT become infertile because of this issue. ITT levels are usually ten times higher than regular blood levels.

Several studies have found that using human chorionic gonadotropin (HCG ) while on TRT can normalize ITT and sperm production in some men (older age and longer pre-exposure to testosterone predicted poorer response). However, the optimum dose and frequency of HCG vary in every man. Fortunately, there are several ways to determine if the dose/frequency of HCG while on TRT is effective: Performing a sperm count/quality test (which requires a 3 month wait period) and/or measuring an upstream hormone to testosterone called 17-hydroxyprogesterone (17OH-P) (which can be measured within 2 weeks of starting HCG). TRT decreases 17OH-P and other upstream hormones due to the shut down of LH (LH is needed to activate the production of these hormones- See figure below). Since HCG mimics LH, using HCG plus TRT may normalize upstream hormones like 17OH-P.

Several studies have found that 17OH-P blood level is correlated to ITT, so testing for this hormone could save time in optimizing HCG dose while waiting for a required 3-month sperm test. The 17OH-P test can also eliminate the need to perform testicular aspirations to measure ITT, which is a very difficult procedure to do and which is reserved to research settings. A study found that a 17OH-P level greater than 6.5 nmol/L (or 215 ng/dL) was found to normalize ITT while using HCG doses of 500 IU every other day plus testosterone enanthate injections given at 200 mg/week. However, only testing sperm count/quality at after 3 months of HCG initiation makes it possible to know for sure if HCG is effective. As men get older and as they are exposed to longer time on TRT, their response to HCG may decrease. These men may need combination approaches using clomiphene and/or FSH (follicle stimulating hormone).

References:
Amory et al. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin suppressed normal men receiving various dosages of human chorionic gonadotropin. Fertility and Sterility. Vol. 89, No. 2, February 2008
For more information on the use of HCG to prevent/reverse testicular atrophy & infertility, and to improve libido in men on TRT.

[Youthful55guy]

I've had a chance to pull the full article and read/analyze it. It's basically a second analysis and of the same data from the same population of 29 male patients they presented in the 2005 paper, which the lead author co-wrote. However there are a couple of differences:

1) In the original paper they did not present the 17-OH Progesterone or Androstenedione data. Given that there's a 3 year difference in publications, I'm assuming that they did not conduct these measurements for the original publication and they went back and did it from frozen samples. Slight differences in the ITT data supports this supposition. It looks like they re-analyzed the samples for ITT as well and came up with slightly different (but corroborating) ITT levels. Probably due to inter-assay differences.

2) Another difference is that in the 2005 paper they compared the changes in the 4 HCG groups to a pooled baseline value for all 4 groups. Whereas, in the 2008 paper, they compared the responses in each group to their own pooled baseline values.

As expected, the two different methods for presenting the ITT data parallel each other and indicate (by my analysis) that the optimum recovery dose for testicular function with HCG is somewhere between 1030 and 1240 IU per week (in divided doses). The 17-OH P4 data also parallels the ITT data (as they concluded), but seems to indicate that a lower HCG dose is necessary for testicular recovery, around 850 IU per week (in divided doses).


They conclude that DHEA is not predictive of testicular recovery, and I tend to agree with that conclusion based on their data. However they conclude that Androstenedione is not predictive, but I disagree with their conclusion based on graphical analysis of their data. In fact, it seems to indicate that a lower dose of HCG is necessary, around 600 IU per week, which seems to be what most guys are using based on trial and error experience.

Also, and I believe more importantly, it demonstrates that HCG probably stimulates the following pathway:

Pregnenolone>Progesterone>17-OH P4>Androstenedione>Testosterone

more so than the alternate pathway:

Pregnenolone>17-OH-Pregnenolone>DHEA>Androstenedione>Testosterone.

Here's a new graph I generated with the 17-OH P4, DHEA, and Androstenedione data presented a little differently than they do in the paper. I feel this type of presentation helps us to interpret the data better with regard to projecting an optimal HCG dose. My take-away is that I plan to continue my 1050 IU per week dose, but that missing up to half the doses would probably not have a perceivable affect.