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25mg of clomiphene citrate effective in treating hypogonadism

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I know we know that it works, but I still thought some actual data may be worth posting ;-)

 

Int Braz J Urol. 2012 Jul;38(4):512-8.

Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study.

Da Ros CT, Averbeck MA.

Source

 

Centro de Andrologia e Urologia, Porto Alegre, Brazil.

Abstract

 

Introduction: Male testosterone deficiency is associated with bad sexual function and quality of life (QoL). The aim of this study was to determine whether a daily dose of 25 mg clomiphene citrate (CC) is effective in stimulating the endogenous testosterone production pathway and to address the applicability of this medication as a therapeutic option for symptomatic hypogonadism. Materials and Methods: This was a prospective study. Men with low sexual desire and testosterone levels (T) below 400 ng/dL were selected to receive CC. Blood samples were obtained to determine baseline measurements of serum T, estradiol, LH, lipid profile and fasting plasma glucose. Each patient was treated with a daily dose of 25 mg CC for at least 3 months. Patients were asked if they experienced any side effects related to the use of CC and if they experienced any improvement in their sexual profile. Paired samples T-test was utilized to analyze responses to therapy. Results: Our cohort consisted of 125 men with hypogonadism and low libido. Mean age was 62 years (± 11.1 years). Serum T levels ranged from 309 ng/dL (baseline, mean value) to 642 ng/dL (3 months after CC initiation, mean value) (p < 0.001). Serum cholesterol levels ranged from 197 to 186 mg/dL (p = 0.003). There were no statistically significant differences when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting plasma glucose and prolactin. All men reported improvements in the post-treatment QoL scores. No serious adverse events were recorded. Conclusions: The CC was effective in stimulating the endogenous production of testosterone. A lower level of total cholesterol was verified after three months of treatment. This medication should be considered as a therapeutic option for some patients with symptomatic male testosterone deficiency.

 

PMID:

22951175

[PubMed - in process]

 

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^ figure from FT

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Guest WangChung
I love it...people thought we were nuts talking about using 25-50mg/day of clomid instead of 150-300mg(!) for PCT...

 

A prominent urologist in San Fran, was scripting this to borderline hypo patients in 2006, when I saw him. He offered me this or test gel. As I carried a hypogonadal diagnosis, I opted to see Dr. Mariano, and initially got on test cyp shots with adjunct hCG (aka Crisler approach) and then later hCG monotherapy (after experimenting on my own).

 

Urologist's name is Turek, and he's published, including re clomid for hypogonadism. He provided me with a draft copy, as he could tell I knew a thing or two about the protocol, among others.

 

I think hCG is far superior for most (I got my TT up to 1496 on hCG + arimidex), but I can understand wanting to take a pill vs. biweekly shots.

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I love it...people thought we were nuts talking about using 25-50mg/day of clomid instead of 150-300mg(!) for PCT...

that are the same people who use ursolic acid supps at the suggested dosing and fool themselves to believe they did anything (at that dosage)

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Just wondering if there would be any problem with small duration uses of clomiphene? A so called kickstarter dose and duration in a mildly eugonadal male. Perhaps 2 weeks.

 

The shortest studies I found were 1 week

 

Enhanced Frequency and Magnitude of Episodic Luteinizing Hormone-Releasing Hormone Discharge as a Hypothalamic Mechanism for Increased Luteinizing Hormone Secretion*

RICHARD J SANTEN and EDWARD B RUBY

 

LH is secreted by the pituitary in a series of pulses which reflect the episodic release of LRH by the hypothalamus in response to neurally mediated processes. This study examined whether gonadal steroids might exert their negative feedback effects on LH secretion by modulating either the frequency or magnitude of LRH pulses. In the absence of sufficiently sensitive plasma LRH assays, we utilized an indirect method to assess LRH secretion by analyzing the frequency and amplitude of plasma LH pulses and simultaneously measuring the acute pituitary sensitivity to exogenous LRH. Ten normal men received clomiphene citrate to interrupt the LH-estradiol negative feedback loop and thereby stimulate LH secretion. This treatment resulted in an increase (P < 0.05) in the frequency of LH pulses observed on day 8 of the study (4.3 ± 0.26 pulses/6 h) compared to basal (3.2 ± 0.25). The amplitude of spontaneous LH pulses also rose during clomiphene from basal levels of 28 ± 3.2 to a maximum of 58 ± 5.3 ng/ml. pulse on day 8 (P < 0.001). This observed increase did not reflect an enhanced pituitary sensitivity to LRH, since clomiphene markedly blunted the acute response to this releasing factor. The divergence between spontaneous pulse height and acute pituitary sensitivity indicated that increased LRH release must be responsible for the high amplitude LH pulses. Similarly, the rise in pulse frequency probably reflects hypothalamic neural events, since episodic secretion is not intrinsic to the pituitary. (J Clin Endocrinol Metab 48: 315, 1979)

 

 

Is significant term dosing aiming to enhance pit sensitivity to LRH?

 

Does longer term dosing tend to enhance pit sensitivity to LRH?

 

And here is a 2 month study.

 

J Clin Endocrinol Metab. 1995 Dec;80(12):3546-52.

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.

Source

Section of Endocrinology, Lahey Clinic, Burlington, Massachusetts 01805, USA.

Abstract

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.

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Do we know if this effect will last for any length of time or is some other part of the axis going to compensate after a week or so?

 

There are a number of +12 month studies that seem to indicate that there is no change to the stimulus over time and that the elevations in LH will remain fairly constant. You might certainly see an increase in E2 as a result however.

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Thanks I recall your thread. How long did you run it and at when did you get tested?

 

I honestly dont remember, i should grab my old thread from M and M and post it here.

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Guest WangChung
There are a number of +12 month studies that seem to indicate that there is no change to the stimulus over time and that the elevations in LH will remain fairly constant. You might certainly see an increase in E2 as a result however.

 

More problematic, ive read that you cant accurately test E2 while on clomid, so if you take an AI, you cant rely on bloods.

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More problematic' date=' ive read that you cant accurately test E2 while on clomid, so if you take an AI, you cant rely on bloods.[/quote']

 

I don't think clomiphene will cause a problem with the estrogen assay...they are chemically/structurally quite different and there are dozens of studies in Pubmed where they appear to be able to measure estrogen levels without a problem in women using clomid.

 

I think the idea that it might stems from the fact that because it causes women to release LH and FSH, clomiphene can cause a false positive pregnancy test because LH and HCG are so similar.

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So I have been dabbling with clom. Have done so in the past. This is just standalone dabbling, not PCT like.

 

I dropped 50mg day one, 15mg day 2, 15mg day 3, zero mg day 4 (forgot), 20mg day 5. I'd probably be aiming for 15-20mg steady state eventually.

 

Anyway I noticed sensitive nipples at the end of my workout, it was a 5pm workout approx. Should I cease completely or just drop down significantly? I am thinking this will be a transient thing but I thought I would ask.

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I love it...people thought we were nuts talking about using 25-50mg/day of clomid instead of 150-300mg(!) for PCT...

I never thought you were nuts B, but I don't recall if I ever said thanks for the heads up on that one. It was and is appreciated.

J

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So I have been dabbling with clom. Have done so in the past. This is just standalone dabbling, not PCT like.

 

I dropped 50mg day one, 15mg day 2, 15mg day 3, zero mg day 4 (forgot), 20mg day 5. I'd probably be aiming for 15-20mg steady state eventually.

 

Anyway I noticed sensitive nipples at the end of my workout, it was a 5pm workout approx. Should I cease completely or just drop down significantly? I am thinking this will be a transient thing but I thought I would ask.

 

I don't think it's related, honestly. Can clomid cause gynecomastia?

 

Sent from my SPH-L720 using Tapatalk

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I am pretty sure it doesn't interact with the E receptors in the breast at all.

 

not sure => " Most estrogenic substances or estrogenic antagonists compete with 16α-[125I]iodo-17β-estradiol for binding to both ER subtypes in a very similar preference and degree; that is, diethylstilbestrol > hexestrol > dienestrol > 4-OH-tamoxifen > 17β-estradiol > coumestrol, ICI-164384 > estrone, 17α-estradiol > nafoxidine, moxestrol > clomifene > estriol, 4-OH-estradiol > tamoxifen, 2-OH-estradiol, 5-androstene-3β,17β-diol, genistein for the ERα protein and dienestrol > 4-OH-tamoxifen > diethylstilbestrol > hexestrol > coumestrol, ICI-164384 > 17β-estradiol > estrone, genistein > estriol > nafoxidine, 5-androstene-3β,17β-diol > 17α-estradiol, clomifene, 2-OH-estradiol > 4-OH-estradiol, tamoxifen, moxestrol for the ERβ protein." from http://endo.endojournals.org/content/138/3/863.short

 

the effects are yet probably irrelevant

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Here is a more recent study on enclomiphene citrate (the trans isomer that makes up ~60% of the racemic mixture in clomid). It performed comparably to testosterone gel. Has the upside of increasing sperm counts compared to the gel, but the downside of pretty significantly increasing estrogen levels (again, compared to the gel).

conv_798.pdf

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That Androxal that they are trying to bring to market as a trt alternative. I can't see that it works any better than regular racemic clomid.

 

I think it's a prescription problem iirc. Clomid technically isn't approved for the treatment of hypogonadism. Although people certainly prescribe it.

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That Androxal that they are trying to bring to market as a trt alternative. I can't see that it works any better than regular racemic clomid.

 

Good point. The two PhD authors on the study are employees of Repros Therapeutics the company bringing Androxal to market. A pretty major conflict of interest that I missed in reading the paper. They give a medical justification for excluding the other isomer in the paper:

 

Zuclomiphene citrate appears to have a longer biological half-life than enclomiphene citrate and thus may persist in the body. It is our hypothesis that the accumulation of the estrogenic zuclomiphene citrate may have pernicious effects on male fertility.

Another study undertaken in the D12 rat hypothalamic cell line showed that enclomiphene citrate antagonized induction of the progesterone receptor, similar to the effects of tamoxifen and raloxifene. Zuclomiphene citrate, however, had agonistic activity more comparable with 17a-ethynyl estradiol or genistein.

 

However, given who their employer is, I think we might have reason to doubt the importance of the agonistic effects of zuclomiphene citrate for hypogonadism.

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