Tamoxifen for Low Testosterone in Males

My previous article discussed the use of clomiphene for increasing testosterone in hypo-gonadal males.  Clomiphene works as an estrogen receptor blocker in the hypothalamus, thus stimulating LH/FSH which then stimulate testicular testosterone production.

Tamoxifen

Another drug which similarly blocks estrogen receptors is Tamoxifen (tamoxiphen), commonly used in breast cancer survivors to block estrogen receptors.   Similar to the use of clomiphene, tamoxiphen has been used to treat low testosterone and low sperm counts (infertility) in males. (1-3)   Usual dosage is 10-20 mg tamoxifen per day for 6 to 9 months.(1-3)

Left Image: tamoxifen chemical structure courtesy of wikimedia commons.

Reduction of Growth Hormone Levels by Tamoxifen

An unwanted effect of tamoxifen is 25% reduction in IGF-1 (growth hormone) levels.(5)  Tamoxifen reduced peak Growth Hormone levels in mice by 60%.(6)

Ocular Toxicity

Adverse effects of tamoxifen relate to the ocular toxicity.  Regular eye exams at the ophthalmology office every 6 months is advised (4)

Articles with related interest:

Clomid for Men with Low Testosterone Part One

Clomid For Men With Low Testosterone, Part Two

References

1) http://www.ncbi.nlm.nih.gov/pubmed/640052
Fertil Steril. 1978 Mar;29(3):320-7.
Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen A, Comhaire F.

The administration of tamoxifen, 20 mg/day for 10 days, to normal males produced a moderate increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels, comparable to the effect of 150 mg of clomiphene citrate (Clomid). However, whereas Clomid produced a decrease in the LH response to LH-releasing hormone (LHRH), no such effect was seen after the administration of tamoxifen. In fact, prolonged treatment (6 weeks) with tamoxifen significantly increased the LH response to LHRL. Treatment of patients with “idiopathic” oligospermia for 6 to 9 months resulted in a significant increase in gonadotropin, testosterone, and estradiol levels. A significant increase in sperm density was observed only in subjects with oligospermia below 20 X 10(6)/ml and normal basal FSH levels. When basal FSH levels were increased or oligospermia was moderate (greater than 20 X 10(6)/ml); no effect on sperm density was seen. As sperm density increased, FSH levels decreased, suggesting an inhibin effect. Sperm motility was not improved by tamoxifen treatment. In five boys with delayed puberty, tamoxifen treatment appeared to activate the pituitary-gonadal axis and pubertal development.

2) http://www.ncbi.nlm.nih.gov/pubmed/18692782
Fertil Steril. 2009 Apr;91(4 Suppl):1427-30.
The effect of selective estrogen receptor modulator administration on the hypothalamic-pituitary-testicular axis in men with idiopathic oligozoospermia.
Tsourdi E1, Kourtis A, Farmakiotis D, Katsikis I, Salmas M, Panidis D.
This study evaluates, compares, and contrasts the effects of three selective estrogen receptor modulators (SERMs), namely, tamoxifen, toremifene, and raloxifene, on the hypothalamic-pituitary-testicular axis in 284 consecutive subfertile men with idiopathic oligozoospermia using three therapeutic protocols: [1] tamoxifen, 20 mg, once daily (n = 94); [2] toremifene, 60 mg, once daily (n = 99); and [3] raloxifene, 60 mg, once daily (n = 91). The antiestrogenic effects of SERMs at the hypothalamic level result in a statistically significant increase of gonadotropin levels, which is more marked for tamoxifen and toremifene compared with raloxifene.

3) Kadioglu, Teoman Cem. “Oral tamoxifen citrate treatment is more effective in normogonadotropic patients who have follicle-stimulating hormone levels within the lower half of normal.” International urology and nephrology 41.4 (2009): 773-776.

ABSTRACT To identify a subgroup of normogonadotropic men who may benefit relatively more from TC (tamoxifen citrate; a widely prescribed drug for male infertility) among those with FSH (follicle-stimulating hormone) values in the lower or higher halves of the normal range.
In this retrospective study, 120 normogonadotropic infertile men with idiopathic oligozoospermia were included. All patients received 20 mg TC daily as a single dose for 6 months, and semen analysis and hormone levels were analyzed after 6 months, with the values being compared with those before treatment.
The FSH, luteinizing hormone and testosterone levels were significantly increased after the use of oral TC 20 mg daily. The sperm counts of the patients in the lower initial FSH group had a significantly higher increase in sperm count and concentration compared to the relatively higher FSH group.
This study revealed that initial FSH values can be used as a marker to estimate the probability that a patient will benefit from oral TC therapy. Patients in the lower FSH group had statistically higher chances of having higher sperm counts after treatment, and it is rational to advise these patients to receive 6 months of oral TC therapy. However, before drawing firm conclusions from this retrospective study, these results should be confirmed with double-blind, placebo-controlled, randomized trials.

4) http://www.nature.com/eye/journal/v13/n6/abs/eye1999217a.html
Eye (1999) 13, 729–733; doi: 10.1038/eye.1999.217
Ocular toxicity in low-dose tamoxifen: A prospective study
Baha’N Noureddin1, Muhieddin Seoud2, Ziad Bashshur1, Ziad Salem2, Ali Shamseddin2 and Ali Khalil2      1Department of Ophthalmology, American University of Beirut, Beirut, Lebanon       2Department of Gynecologic, Oncology American University of Beirut, Beirut, Lebanon
Purpose To look at the incidence, symptomatology, course and reversibility of low-dose tamoxifen ocular toxicity.
Methods Sixty-five women with breast cancer, on tamoxifen oral therapy (20 mg/day), and a totally normal eye examination, were prospectively followed up. A full ophthalmic evaluation was done every 6 months, for a median of 30 months (range 4-79 months). Any sign of toxicity in the cornea, lens, retina or optic nerve was looked for, whether associated with a change in visual acuity or not.
Results Ocular toxicity was documented in 8 patients, giving an incidence of 12%. Seven patients had keratopathy in the form of subepithelial deposits, whorls and linear opacities. Three of these patients had a concurrent symptomatic bilateral pigmentary retinopathy that warranted discontinuation of therapy. One patient developed bilateral optic neuritis that left her with optic nerve pallor and a decrease in vision. The patients who had the toxicity had a significantly higher tamoxifen cumulative dose (p = 0.03), and were longer on treatment (p = 0.04), than the non-affected ones. The keratopathy changes were reversible upon discontinuation of the drug.
Conclusion Prompt reporting of symptoms and yearly ophthalmic examinations are mandatory in patients on tamoxifen to detect toxic effects while these are still reversible.

5)Birzniece, Vita, et al. “Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men.” The Journal of Clinical Endocrinology & Metabolism 95.12 (2010): 5443-5448.

Jeffrey Dach MD
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