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Testosterone versus clomiphene citrate for treatment of hypogonadism or low testosterone in men

Hypogonadism, or low testosterone levels, can cause a variety of symptoms in men, including fatigue, decreased libido, and muscle loss. While both clomiphene citrate (CC) and testosterone supplementation therapy (TST) are effective treatments for hypogonadism, it is unclear which therapy is more effective. To compare the two treatments, we recruited men with hypogonadism and randomly assigned them to receive either CC or TST. We then assessed changes in symptoms and treatment efficacy before and after receiving CC and TST. Our results showed that both CC and TST are effective treatments for hypogonadism, with no significant difference in efficacy between the two treatments. However, TST was associated with greater improvements in some symptoms, such as fatigue and muscle loss. Therefore, TST may be the preferred treatment for men with hypogonadism who are particularly bothered by these symptoms.

Idiopathic age-related decline in testosterone, or IADT, is a condition that currently affects close to 40% of adult males aged 45 and older. While the cause of IADT is still unknown, research suggests that it may be due to a combination of factors, including changes in the hypothalamic-pituitary-gonadal axis, alterations in gonadotropin secretion, and/or testicular dysfunction. IADT can lead to a number of different symptoms, including fatigue, decreased libido, erectile dysfunction, reduced muscle mass and strength, and depression. While there is currently no cure for IADT, there are a number of treatment options available that can help to improve symptoms and quality of life. If you think you may be experiencing symptoms of IADT, it is important to speak with your healthcare provider.

Testosterone levels generally peak in early adulthood and then gradually decline with age. However, some men experience a more rapid decline in testosterone, which can lead to a number of health problems. Common symptoms of testosterone deficiency include fatigue, erectile dysfunction, diminished libido, and a decrease in concentration. Testosterone replacement therapy can help to alleviate these symptoms and improve quality of life. However, it is important to consult with a healthcare professional to determine if testosterone therapy is right for you.

Clomiphene citrate (CC), also known as Clomid, is a medication commonly used to treat fertility issues in women. However, CC is also frequently used off-label for the treatment of hypogonadism in men who wish to preserve their reproductive function. CC is a selective estrogen receptor modulator, meaning that it binds to estrogen receptors and alters their activity. In the case of CC, it antagonizes the negative feedback of estradiol at the hypothalamus and pituitary, thereby enhancing the release of follicle stimulating hormone (FSH) and luteinizing hormone. This increase in FSH and LH can then stimulate testosterone production by the testes, leading to increased levels of circulating testosterone. While CC is generally well-tolerated, side effects can include hot flashes, visual changes, nausea, and breast tenderness. Overall, CC is an effective option for the treatment of hypogonadism in men who wish to preserve their reproductive function.

Clomiphene citrate (CC) is a selective estrogen receptor modulator (SERM) that has been used for ovulation induction in female infertility for over 40 years and has more recently been approved for treatment of hypogonadism in men. CC has mixed agonist/antagonist effects on estradiol receptors in different tissues, i.e. it acts as an agonist on the hypothalamus-pituitary while acting as an antagonist on the pituitary-gonadal axis. This unique mechanism of action allows CC to increase serum testosterone levels by increasing gonadotropin release from the pituitary while simultaneously competitively inhibiting negative feedback of estradiol at the hypothalamus. CC has been shown to be effective in inducing ovulation in women with ovulatory disorders and restoring serum testosterone levels back to the normal range in men with hypogonadism. Furthermore, CC has a long half-life and can maintain therapeutic serum testosterone levels for up to 3 years with once daily dosing. Therefore, CC may be a useful option for treating hypogonadal symptoms while avoiding the potential risks associated with testosterone replacement therapy.

Our study provides compelling evidence that TST is more effective than CC in treating hypogonadism. While both medications were able to raise serum testosterone levels, TST was superior in terms of symptom relief. In particular, patients on TST reported significantly Better results in terms of libido, energy levels, and mood. CC, while still an effective treatment, appeared to have a negative impact on libido. This is an important finding, as libido is a key component of quality of life for men with hypogonadism. Overall, our study indicates that TST is the better option for treating hypogonadism. However, further studies are needed to confirm the long-term safety and efficacy of TST.

Clomiphene citrate Lozenges have better bioavailability and these bypasses the first pass effect or metabolism in the liver.

To Know more about compounding for Testosterone replacement using natural Bioidentical testosterone or clomiphene citrate please call Pharmaprodia at 623-404-1000 and talk to one of our talented Compounding Pharmacists and/or Dr Richard Nkwenti, R.Ph; IMD; Ph.D; Board certified in anti aging Medicine and a Fellow in Anti aging, Metabolic and Functional Medicine.


Dadhich P, Ramasamy R, Scovell J, Wilken N, Lipshultz L. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men. Indian J Urol. 2017;33(3):236-240. doi:10.4103/iju.IJU_372_16