Well I'm taking a break and posting the studies anyways
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
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
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
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 hormonal disturbances of the gonadal axis in uremic patients.
Fertil Steril 2003 Jan;79(1):203-5 Related Articles, Links
Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse.
Tan RS, Vasudevan D.
Department of Family and Community Medicine, University of Texas Health Sciences Center, Houston, Texas 77030, USA.
[email protected]
OBJECTIVE: To report a case of symptomatic hypogonadism induced by the abuse of multiple steroid preparations that was subsequently reversed by clomiphene. DESIGN: Case report. SETTING: University-affiliated andrology practice within family practice clinic. PATIENT(S): A 30-year-old male. INTERVENTION(S): Clomiphene citrate, 100-mg challenge for 5 days, followed by treatment at same dose for 2 months. MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen decline in aging male questionnaire, total T, FSH, LH. RESULT(S): [/b]Reversal of symptoms, normalization of T levels with LH surge, restoration of pituitary-gonadal axis. [/b]CONCLUSION(S): Clomiphene citrate is used typically in helping to restore fertility in females. This represents the first case report of the successful use of clomiphene to restore T levels and the pituitary-gonadal axis in a male patient. The axis was previously shut off with multiple anabolic steroid abuse.
Fertil Steril 1997 Apr;67(4):783-5
Comment in:
Fertil Steril. 1997 Oct;68(4):745.
Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate.
Burge MR, Lanzi RA, Skarda ST, Eaton RP.
University of New Mexico School of Medicine, Department of Medicine/Endocrinology-5ACC, Albuquerque 87131, USA.
OBJECTIVE: To assess the efficacy of estrogen antagonist therapy on the function of the hypothalamic-pituitary-testicular axis in a young male runner with significant morbidity attributable to idiopathic hypogonadotropic hypogonadism. DESIGN: An uncontrolled case study. SETTING: The outpatient endocrinology clinic of a university tertiary referral center. PATIENT(S): A 29-year-old male who has run 50 to 90 miles per week since 15 years of age and who presented with a pelvic stress fracture, markedly decreased bone mineral density, and symptomatic hypogonadotropic hypogonadism. INTERVENTION(S): Clomiphene citrate (CC) at doses up to 50 mg two times per day over a 5-month period. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, and T before and after CC therapy, as well as clinical indicators of gonadal function. RESULT(S): Barely detectable levels of LH and FSH associated with hypogonadal levels of T were restored to the normal range with CC therapy. The patient experienced improved erectile function, increased testicular size and sexual hair growth, and an improved sense of well being. CONCLUSION(S): Exercise-induced hypogonadotropic hypogonadism exists as a clinical entity among male endurance athletes, and CC may provide a safe and effective treatment option for males with debilitating hypogonadism related to endurance exercise.
PMID: 9093212 [PubMed - indexed for MEDLINE]
: J Clin Endocrinol Metab 1995 Dec;80(12):3546-52 Related Articles, Links
Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate.
Guay AT, Bansal S, Heatley GJ.
Section of Endocrinology, Lahey Clinic, Burlington, Massachusetts 01805, USA.
Secondary hypogonadism is not an infrequent abnormality in older patients presenting with the primary complaint of erectile dysfunction. Because of the role of testosterone in mediating sexual desire and erectile function in men, these patients are usually treated with exogenous testosterone, which, while elevating the circulating androgens, suppresses gonadotropins from the hypothalamic-pituitary axis. The response of this form of therapy, although extolled in the lay literature, has usually not been effective in restoring or even improving sexual function. This failure of response could be the result of suppression of gonadotropins or the lack of a cause and effect relationship between sexual function and circulating androgens in this group of patients. Further, because exogenous testosterone can potentially increase the risk of prostate disease, it is important to be sure of the benefit sought, i.e. an increase in sexual function. In an attempt to answer this question, we measured the hormone levels and studied the sexual function in 17 patients with erectile dysfunction who were found to have secondary hypogonadism. This double blind, placebo-controlled, cross-over study consisted of treatment with clomiphene citrate and a placebo for 2 months each. Similar to our previous observations, LH, FSH, and total and free testosterone levels showed a significant elevation in response to clomiphene citrate over the response to placebo. However, sexual function, as monitored by questionnaires and nocturnal penile tumescence and rigidity testing, did not improve except for some limited parameters in younger and healthier men. The results confirmed that there can be a functional secondary hypogonadism in men on an out-patient basis, but correlation of the hormonal status does not universally reverse the associated erectile dysfunction to normal, thus requiring closer scrutiny of claims of cause and effect relationships between hypogonadism and erectile dysfunction.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 8530597 [PubMed - indexed for MEDLINE]
This one is thanks to raybravo:
Abstract 798 MSSE Suppl 2000
Pharmaceutical intervention of anabolic steroid induced hypogonadism – our success at restoration of the hpg axis
Scally C, Street C
High-dose anabolic-androgenic steroid (AAS) administration results in hypogonadotropic hypogonadism (HH). Physical manifestations can include one or more of the following: depression, decreased sexual desire, impotence, feelings of apathy, testicular atrophy, and loss of muscle mass and strength. Due to feedback inhibition, laboratory values drop well below established physiologic norms: leutinizing hormone (LH) > 3.6 IU/L, follicle stimulating hormone (FSH) > 2.25 IU/L, and testosterone y 300 ng/dL. A search of the literature reveals an absence of studies dealing specifically with AAS-induced HH, and restoration of normal endocrine function.
We report on two interesting cases of AAS using bodybuilders who were brought out of the hypogonadal state. Blood samples were taken in the morning for both subjects and analysed using chemiluminescence (Quest diagnostics, Irving, TX). Post therapy samples were taken 15 days after the last HCG injection.
Case I: 6’0’’ 206 lbs., 33 years old Caucasian male with a 10+ year history of steroid-administration for bodybuilding and Powerlifting. By his own admission he was a “heavy” user, taking from 500 mg/week to 2+ grams/week. Pre-treatment values: LH>1.0 IU/L, T 191 ng/dL. One course of therapy (32 days) was given: 2,500 IU of HCG every 4 days (8 injections total), 50 mg clomifen bid and 10 mg tamoxifen qd. Despite massive drug use patient was an exceptionally good responder. Post-treatment values: LH 5.2 IU/L, T 1072 ng/dL.
Case 2: 5’10’’ 184 lbs, 36 years old Caucasian male with a 2 year history of continuous nandrolone use (200-400 mg/week). Pre treatment values: LH >1.0 IU/L, T 45 ng/dL. Treatment I (32 days): 2,500 IU HCG every 4 days (8 total), clomifen 50 mg bid, arimidex 1 mg qd. Post values: LH > 1.0 IU/L, T 38 ng/dL. Treatment 2 (60 days): 5,000 IU HCG every 4 days (4 inj. total), followed by 2,500 IU HCG every 4 d (4 inj. total), clomifen (50 mg bid) and tamoxifen (10 mg qd). Post-values: LH > 1.4 IU/L, T 63 ng/dL. Treatment 3 (32 days): 5,000 IU HCG qod (6 inj. total) followed by 2,500 IU HCG qod (6 inj. total) given simultaneously with menotropins 150 IU qod (6 inj. total), clomifen (50 mg bid) and tamoxifen (10 mg bid). Post-values: LH 9.8 IU/L, T 507 ng/dL.
Restoration of the HPG axis, even in severe cases of hypogonadism, is possible with combined therapies and careful monitoring of the patient. With continued popularity of these drugs, long-term androgen deficiency is a health concern for former AAS users. Further research is needed in this area.
Nelson stated some probs with some of these studies, and I had rebuttles to his arguments, some of the problems seemed sort of nit-picky to me, but before I go and cut and paste my rebuttles I let you guys take a look at them and see what you think of them. BTW tomorrow I'll post the studies on proviron.
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Nice to see you getting along. I'm going to cry.
