Clomid isomer isolation - new trt option?

Discussion in 'Men's Health Forum' started by Jimmyinkedup, Mar 12, 2013.

  1. #1
    Jimmyinkedup

    Jimmyinkedup Active Member

    I recently read that they are working on isolating the more active Enclomiphene isomer to test as a more effective trt option that regular clomid which consists of the aforementioned E isomer and less active Z isomer.
    Im interested in this for multiple reasons but one is im curious to see if the removal of the isomer with both agonist an antagonist estrogenic effects improves its effectiveness or lessens it. The expression of the Z isomer apparently in some research has more impact of fsh while the E isomer on LH - not sure if this will be good or bad. Obviously bad for fertility purposes but as trt option will be interesting to see.

    this is the product : Repros Therapeutics
    the study: Enclomiphene, an estrogen receptor antagonist for the... [IDrugs. 2009] - PubMed - NCBI
     
  2. #2
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    It should be noted the COI of the corresponding author. RD Wiehle is a RPRX employee (one of about 6) who undoubtedly contributed only to the writing of the article, no more. Further, the very selective data used for the report. In fact, this attempt at selective use of data led to RPRX problems in their current clinical site studies. RPRX asked but was denied by the FDA to exclude data on sperm counts, which were consistent with published data on topical testosterone. RPRX selected use of data on sperm counts is important since this is the endpoint needed for FDA Approval, NOT serum testosterone.

    Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel. The Journal of Sexual Medicine. Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel - Kaminetsky - 2013 - The Journal of Sexual Medicine - Wiley Online Library

    Introduction - clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism.

    Aim - Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone.

    Main Outcome Measures - Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 igf-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated.

    Methods - This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone.

    Results - After discontinuation of topical testosterone, morning TT values averaged 165?±?66?pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545?±?268 and 525?±?256?pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334?×?106/mL range. The gel was ineffective in raising sperm counts above 20?×?106/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts.

    Conclusions - Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.


    Note: Corresponding Author: Ronald D. Wiehle, PhD, Repros Therapeutics, 2408 Timberloch Place, B-7, The Woodlands, TX 77380, USA. Tel: 281-719-3406; Fax: 281-719-3446; E-mail:
    Code:
    rwiehle@reprosrx.com
     
  3. #3
    Jimmyinkedup

    Jimmyinkedup Active Member

    Thank You Dr Scally!
     
  4. #4
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Podolski [RPRX CEO] is now admitting one of his clinical trial sites committed data fraud, which the company allegedly caught and fixed. Huh? https://twitter.com/adamfeuerstein
     
  5. #5
    Jimmyinkedup

    Jimmyinkedup Active Member

    WOW! One can only wonder how often this occurs??
    I was hoping to get your input on this thread and had lost hope. Thanks for posting the info you are. Very enlightening ..
     
  6. #6
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    One has to look no further than this forum to question the results. RPRX has a long long history of selective data PR. This is no exception. What about Patient Reported Outcome (PRO) for libido, erection, ... If these were not done, why would the FDA approve a drug where there is no apparent problem (non-inferiority). SERMs adversely affect libido, etc. But, RPRX is not reporting anything!!! In fact, any PRO is absent.
     
    Last edited: Mar 28, 2013
  7. #7
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

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