By Greg McKettrick RPh
Clinical Liaison – Men’s Health
Revelation Pharma

Testosterone replacement therapy and anti-aging treatments are in extreme demand due to current trends in fitness, or lack thereof, that permeates our society. As a whole, our routine diet and level of activity is very poor, and the effects are obvious. We are seeing dramatic increases in obesity and comorbidities that go along with it. Many patients are turning to the new weight loss wonder drugs as a quick fix, but the underlying issues of a healthy body and healthy lifestyle are of principle importance. Hormone levels and body composition change as we age, but we have means to address these issues and improve our quality of life and vitality.

Related men's health resources

  • Pharmacist Formulations has supplements and more developed by pharmacists specifically for needs of men at all stages of life.
  • For information on erectile dysfunction and similar issues — and ways to manage them — Penile Rehabilitation Protocol has a wealth of information.
  • Learn more about clomiphene and enclomiphene from pharmacist Greg McKettrick's webinar "Men’s Health: Clomiphene and Enclomiphene".
  • Consult with a compounding pharmacist through ConsultRx. Talk to an expert in men's health who can work with your existing healthcare team to find the root cause of your health issues using a functional and holistic coaching approach.

For many men, testosterone has been, is, and will be the go-to answer to address the symptoms of aging and physiologic decline. Loss of bone and muscle mass, low energy and libido, loss of physical and sexual function, and cognitive decline are some of the primary concerns. (1) Therapy with testosterone replacement is a crucial option, but there are factors to keep in mind before initiating therapy. Our bodies are like glorious and complex machines that have been meticulously designed and incorporate a sophisticated onboard computer system. As our body ages and hormone production changes, we go through a myriad of physiological and chemical adaptations. In the same manner, when we initiate therapy to increase a hormone, like testosterone, our body reads the increased level and follows a feedback pathway in response. The result of this feedback is our onboard computer notifying our system of the presence of higher levels of testosterone and sending instructions to halt production since the system now has a sufficient supply. In short, initiating exogenous testosterone therapy signals the testes to shut down production of endogenous testosterone. The process involves the inhibition of GnHR (Gonadotropin-Releasing Hormone) and leads to downstream inhibition of LH (Luteinizing Hormone) and FSH (Follicular Stimulating Hormone) which are necessary for natural testicular function. (2)

In addition to the reduction in endogenous testosterone production, the testicles also produce less sperm. While TRT has the desired effects on our symptoms of low T, it adversely effects testicular size, spermatogenesis, and fertility. For men who are planning to have children, this can be a huge obstacle on the path to addressing their medical concerns. There are alternatives for men seeking to improve their testosterone levels while maintaining fertility and testicular volume, and the most effective, affordable, and accessible of the options are Selective Estrogen Receptor Modulators (SERMs). SERMs block negative feedback from estrogen in the hypothalamus causing LH production and FSH release to increase which stimulates testosterone production and spermatogenic functions in the testes while eliminating the issues of aromatization associated with TRT. (3) The common SERMs for men are Clomiphene Citrate and Enclomiphene Citrate.

Clomiphene Citrate is a fertility medication for women but has been used successfully to boost fertility in sub-fertile men for over 50 years increasing pregnancy rates by 40%. (4) In addition to protecting, or improving fertility, clomiphene can provide the benefits associated with increased testosterone levels without causing the negative side effects like changes to hematocrit and hemoglobin, PSA or cholesterol levels. (5) Clomiphene has some side effects (mood changes/gynecomastia/headache/nausea) and won’t have as significant an effect on testosterone levels on men with naturally higher LH levels, but it is a good alternative for men wanting to protect testicular function.

Clomiphene is a mixture of two components, or diastereoisomers. Zuclomiphene accounts for roughly 1/3 of the whole compound and has a very long half-life (30 days) while the other component, Enclomiphene, has a half-life of only 10 hours. Enclomiphene is not available commercially but is available through compounding pharmacies. Of the two components, Enclomiphene is considered the “cleaner” option because it has a much lower side effect profile than clomiphene due to the abbreviated half-life. While protecting and improving fertility, Enclomiphene also has the capacity to boost testosterone levels as well as a daily application of 50mg Testosterone gel. (6) Based on this, Enclomiphene may be the ideal option for hypogonadal men especially if they are seeking to protect and maintain fertility.

For more information on Men’s Health and Sexual Function, check out our website at and consider scheduling a consultation with one of our clinical specialists.


  1. J Adv Pharm Technol Res. 2010 Jul-Sep; (3) 297-201, doi: 10.4103/0110-5558.72420
  2. American Society for Reproductive Medicine ; Testosterone Use and Male Infertility, J.B Younger, 2015
  3. SC Krastek, RP Smith. Non-testosterone management of male hypogonadism: an examination of the existing literature. Translational Andrology and Urology, Vol 9, Supplement 2;March 5, 2020
  4. Paulson DF, Hammond CB, de Vere White R, Wiebe RH. Clomiphene Citrate: Pharmacologic treatment of hypofertile male. Urology, 1977;9:419-421
  5. Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism, efficacy and treatment cost. J Sex Med 2010;7:269-76
  6. Wiehle R, Cunningham GR, Pittleloud N, Wike J, Hsu K, Fontenot G, Rosner M, Dwyer A, Podolski J. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: a pharmacodynamic and pharmacokinetic study; BJU Int 2013 Dec; 112(8): 1188-1200