I have found some studies showing the effectiveness of clomiphene citrate and tamoxifen citrate. Some of these studies I found on this board. I hope this will help.
Study 1
Studies showing the effectiveness of Clomid
J Clin Endocrinol Metab 1985 Nov;61(5):842-5
Evidence for a role of endogenous estrogen in the hypothalamic control of gonadotropin secretion in men.
Winters SJ, Troen P.
To examine the mechanism by which endogenous estrogens inhibit gonadotropin secretion in men, blood samples were drawn every 10 min for 12 h in five men before and at the completion of 3 weeks of treatment with the estrogen antagonist clomiphene citrate (50 mg twice daily). Samples were analyzed for LH and alpha-subunit by RIA. Clomiphene produced a 3-fold rise in circulating LH levels, which was associated with a 80% increase in pulse frequency and a 70% increase in pulse amplitude. Immunoreactive alpha-subunit secretion was also pulsatile before and after clomiphene treatment. Mean alpha-levels rose 70%, together with a 39% increase in pulse frequency and a 41% increase in pulse amplitude. Circulating testosterone and estradiol levels increased 2-fold and FSH levels increased 3-fold after clomiphene treatment. Insofar as each LH and uncombined alpha-subunit pulse reflects a LHRH secretory episode, our data indicate that endogenous estrogens tonically restrain the hypothalamic release of LHRH. From these results and those of previous studies, we conclude that estrogens as well as androgens are important in the testicular feedback inhibition of the hypothalamic oscillator that governs pulsatile gonadotropin secretion.
J Androl 1991 Jul-Aug;12(4):258-63
Study 2
The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men.
Tenover JS, Bremner WJ.
Department of Medicine, University of Washington School of Medicine, Seattle.
Serum androgens decline with age in normal men, despite normal or elevated bioactive serum gonadotropins, suggesting that primary testicular dysfunction occurs with aging. The authors further assessed the question of age-related testicular dysfunction by evaluating whether raising serum gonadotropins above the normal serum range for an extended time in healthy elderly men might result in bringing their gonadal function to a level similar to that found in young adult men. Five elderly (65 to 85 years old) and five young adult men (26 to 33 years old) were given 50 mg of clomiphene citrate (CC) twice a day for 8 weeks to stimulate gonadotropin production. During that time, testosterone (T), non-sex hormone-binding globulin bound T, and estradiol increased significantly in both age groups, while serum inhibin increased significantly only in the young adult men. The increases in serum androgens with CC administration were significantly greater in the young adult men than in the elderly men. These hormone changes occurred in the setting of serum gonadotropins that increased significantly in both age groups, although there was a tendency for the elderly men to have a smaller increase in luteinizing hormone. Despite 8 weeks of stimulation of the pituitary-gonadal axis by CC administration, the elderly men demonstrated significantly diminished testicular responses compared with the young adult men. Sertoli cell function, as determined by inhibin production, was more diminished in the elderly men than was Leydig cell function. These data strengthen the hypothesis that normal aging in men is accompanied by a decline in testicular function.
Urology 1991 Oct;38(4):317-22
Study 3
1: Fertil Steril. 1978 Mar;29(3):320-7.
Related Articles, Links
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.
Study 4
One recent case report involved the reversal of a hypogonadal state in a man who'd previously used nandrolone decanoate, stanozolol, and methenolone for several months. The man complained of common hypogonadal symptoms ( i.e., loss of libido, fatigue, depression, etc.) and upon investigation his total and free Testosterone levels were 71 ng/dl and 29 pg/ml respectively. (The reference ranges were 260-1000 ng/dl and 34-194 pg/ml, by the way.)
He was then given 100 mg of clomiphene for 5 days and reevaluated 2 weeks later. He reported an improvement in mood, energy, and libido and his total Testosterone was 828 ng/dl. However, after a follow up 2 months later, his symptoms had returned and his total Testosterone concentration was 301 ng/dl. In other words, he suffered a relapse.
They then gave the man 100 mg per day for 2 months and then reevaluated his blood work. They found his total Testosterone was 705 ng/dl and no relapse occurred in subsequent blood work. A similar case reported restoration of the HPTA using the same dosage of clomiphene over a 5 month period.
Study 5
Possible hypothalamic impotence. Male counterpart to hypothalamic amenorrhea?
Guay AT, Bansal S, Hodge MB.
Section of Endocrinology, Lahey Clinic Medical Center, Burlington, Massachusetts.
Twenty-one men with erectile complaints who were found to have a low level of serum testosterone without a reciprocal elevation of the serum levels of luteinizing hormone were evaluated to identify whether the defect was of hypothalamic or of pituitary origin. Patients underwent a luteinizing hormone (LH)-follicle-stimulating hormone (FSH)-releasing hormone stimulation test that showed a normal but sluggish increase in LH and FSH levels, thus ruling out a pituitary defect and suggesting a suprapituitary abnormality. This was confirmed when, in response to clomiphene, patients had a normal increase in gonadotropin and testosterone levels. Although the basal as well as clomiphene and gonadotropin releasing hormone-stimulated levels of total testosterone and gonadotropins were identical in men less than and more than fifty years old, the elevation of free testosterone levels in response to clomiphene was higher in patients younger than fifty. This suggested that although the primary abnormality found in these patients is altered secretion of gonadotropin hormone-releasing hormone from the hypothalamus, an age-related decline in the responsivity of Leydig cells to LH may make it more manifest in older patients. Elevation of testosterone levels from a subnormal to a normal range in response to clomiphene administered for seven days suggests that the defect is functional and reversible and that the drug may be useful in treatment of sexual dysfunction in this group of patients.
Nephron 1993;63(4):390-4
Study 6
Effect of clomiphene citrate on hormonal profile in male hemodialysis and kidney transplant patients.
Martin-Malo A, Benito P, Castillo D, Espinosa M, Burdiel LG, Perez R, Aljama P.
Department of Nephrology, Hospital Universitario Reina Sofia, Cordoba, Spain.
The aim of this study was to evaluate the role of clomiphene citrate (CC) therapy in the hypothalamus-pituitary-gonadal axis of male uremic subjects. Thirty-four patients on hemodialysis (HD) and 8 successful kidney transplant subjects (RT) were evaluated. Nine healthy males were used as controls (C). At baseline, zinc, testosterone (TEST), prolactin (PRL), FSH, LH and estradiol plasma concentrations were measured. All subjects were treated with CC (100 mg/day) for a week. The aforementioned parameters were determined again on the seventh day of CC therapy, and 3 days after drug withdrawal. Following CC, there was a rise in FSH, LH and TEST levels in all subjects (p < 0.05); it is interesting to stress that TEST became normal in HD. In addition, we observed a decrease of PRL after CC only in HD patients (p < 0.01). In summary, CC was able to partially correct most of the
Study 7
Affiliation
Department of Urology, Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Abstract
OBJECTIVE: To identify a subgroup of men who may benefit from tamoxifen citrate (a widely prescribed drug for male infertility) among those with normogonadotrophic and hypergonadotrophic oligozoospermia, either idiopathic or after varicocelectomy. PATIENTS AND METHODS: The study included infertile men with oligozoospermia, 136 referred to our outpatient clinic and 84 infertile after varicocelectomy. All patients received tamoxifen citrate (10 mg twice daily); semen analysis and hormone tests were repeated at the end of 3 and 6 months of treatment, the values being compared with those before treatment. RESULTS : The levels of follicle-stimulating hormone, luteinizing hormone and testosterone increased in all groups receiving tamoxifen citrate. Normogonadotrophic patients had a significant increase in sperm count and concentration, while the slight increase detected in the hypergonadotrophic group was statistically insignificant. CONCLUSION: In patients with normogonadotrophic oligozoospermia, tamoxifen citrate may be offered as a practical and economic alternative before using any assisted reproduction techniques. However, double-blind placebo-controlled trials are needed to confirm the findings of this preliminary study.
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"Study on benefit of tamox-again pay attention to duration. Also notice levels were checked at 2wks-12wks, but it is not specified when increased levels of FSH, LH, and T were seen at maximized effect. Levels of T and FSH are only significant, with T at miniscuel proportions
Fertil Steril. 1983 May;39(5):700-3. Related Articles, Links
Study 8
Increased sperm count in 25 cases of idiopathic normogonadotropic oligospermia following treatment with tamoxifen.
Buvat J, Ardaens K, Lemaire A, Gauthier A, Gasnault JP, Buvat-Herbaut M.
Twenty-five subfertile men, all presenting with idiopathic normogonadotropic oligospermia, were treated with tamoxifen (20 mg/day) for 4 to 12 months. Semen analysis was performed twice before treatment and at least twice after 3 to 12 months of treatment. In 14 patients, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and plasma testosterone (T) were assayed before treatment, then again after 2 weeks and 12 weeks of treatment. Semen volume, sperm motility, and sperm morphologic characteristics were not modified by tamoxifen. Conversely, a twofold increase of both the mean sperm concentration and the mean total sperm count per ejaculate was observed during treatment (P less than 0.001). Mean values of T, LH, and FSH increased during treatment, but the difference was only significant for T (P less than 0.001) and FSH (P less than 0.05). Ten pregnancies (40% of cases) were reported during the 161 months of treatment.
Study 9
This observational study documents the treatment protocol of HCG, clomiphene citrate, and tamoxifen in returning hormonal function to normal post AAS usage. Design: Five HIV-negative males age 27-49, weighing 77-100 kg, with serum total testosterone levels below 240 ng/dL and luteinizing hormone (LH) levels below 1.5 mIU/mL were considered for this observational study. All five patients were administered the treatment protocol.
Quote:
Treatment consisted of combination therapy which included concurrent administration of (a) Human Chorionic Gonadotropin, (b) Clomiphene Citrate and (c) Tamoxifen Citrate for a standard duration of 45 days. This protocol was repeated with every patient until serum LH and total testosterone values reached normal ranges... All five patients were considered eugonadal by normal laboratory reference ranges by the conclusion of treatment. Average serum total testosterone rose from 98.2 to 692.8 ng/dL (p<.001) while the average serum LH rose from an average undetectable value of less than 1.0 to 7.92 mIU/mL (p<.0008).
Quote:
Conclusions: Although the treatment protocol of HCG, clomiphene citrate, and tamoxifen proved beneficial in reversing AAS induced hypogonadotropic hypogonadism, future controlled studies need to be performed to confirm the beneficial effects of this combined pharmacotherapy in returning HPGA functioning to normal.
Study 10
William Llewellyn and the study referenced was 1. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen, Comhaire. Fertil and Steril 29 (1978) 320-7)
Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using Nolvadex instead of Clomid for increasing testosterone levels (1). Here, researchers looked the effects of Nolvadex and Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant. What was found, just in the early parts of the study, was quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum testosterone levels to 142% of baseline, which was on par with the effect of 150mg of Clomid daily for the same duration (the testosterone increase was slightly, but not significantly, better for Clomid). We must remember though that this is the effect of three 50mg tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the Nolvadex side.
Pituitary Sensitivity to GnRH
But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The tests showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.
