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Clomid~clomiphene citrate (updated 2013)

heavyiron

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Clomid~clomiphene citrate
Clomid

(clomiphene citrate)

Clomiphene citrate (Clomid) is a SERM (selective estrogen receptor modulator) similar to Tamoxifen. Clomid is typically used to induce ovulation in females by blocking estrogen in selective tissue in the body. Clomid opposes the negative feedback of estrogens on the Hypothalamic Pituitary Ovarian Axis which enhances the release of LH and FSH.

Post cycle recovery

I consider Clomid an important recovery drug for post cycle therapy. In men, the effects of Clomid are much more pronounced than women as an increase in FSH and LH will cause a rise in natural Testosterone. After just 7 days of clomiphene citrate administration (100mg daily), mean serum total T and non-SHBG-bound levels in young men increased by a whopping 100% and 304%, respectively, while in older men these values increased by only 32% and 8%, Similar to previous observations, LH and FSH levels showed a significant elevation in response to clomiphene citrate over the response to placebo.

Clomid is a very useful compound at the end of an AAS cycle because Testosterone quickly falls below baseline levels when steroids are withdrawn. This decline in Testosterone then allows the effects of cortisol to wreak havoc on new muscle. The user quickly goes from an anabolic to a catabolic state. Thankfully this crash can be mitigated with Clomid. Clomiphene restores normal Testosterone levels and improves sperm motility in most male patients. Clomid may also be used on cycle to block the effects of estrogen in male breast tissue therefore reducing the likelihood of gynecomastia however Nolvadex seems the preferred medicine for this purpose. Additionally, Clomid supports improved cardiovascular values.

So how do we maximize the benefits of this recovery medicine? First we need to determine the clearance time of the AAS being used. In other words, how long will it take for the steroid to reach baseline Testosterone levels? Most steroids have a published duration in which they are no longer elevating Testosterone above natural levels but this is only an estimate as cycle duration, scar tissue and many multiple depots may extend release times of the AAS administered when using injectable compounds. Once it's determined when to employ Clomid, therapy should be about 4-6 weeks in duration. I like to start with a dose of 50-100mg's daily for 3 weeks and then reduce that dose to 50mg daily the remainder of the therapy. I recommend getting labs after Clomid therapy to determine if recovery was successful. If not, another Clomid course may be needed.

SERM's and female fat reduction?

Some women report a reduction in female pattern fat deposits when employing a SERM during an anabolic androgenic steroid cycle but evidence seems to be to the contrary according to a study on Nolvadex that measured body fat using a dual-energy X-ray absorptiometry (DXA). Body fat increased with Nolvadex use alone. It is likely that the lower body fat observed may be due to the steroid administration not the SERM by itself.

Hypogonadism and low libido

In 2012, 25mg daily Clomid administration was investigated for mitigating low male Testosterone levels and poor sexual function. Essentially the researchers studied Clomid as a treatment for hypogonadism. This treatment lasted for at least 3 months. The Clomid treatment was successful, resulting in about a two times increase of the men's Testosterone levels and improvements in sexual function. Clomid may be considered a therapeutic option for patients with symptomatic male Testosterone deficiency. The chart below provides the Testosterone outcomes by age from this 25mg daily treatment.

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All participants reported an improvement in quality of life although younger men more so than older men. Restoring men's Testosterone levels with Clomid increases sexual function and quality of life.

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Side effects

Clomid users have reported various side effects like dizziness, vision problems, emotional swings and nausea. I have personally had mild vision issues while on Clomid but they went away when I stopped using the medicine.

Overall Clomid is a relatively safe compound when used at reasonable dosages and in my estimation is a good option for proper Testosterone recovery and improved sexual function.


References
1. Body composition measurements using DXA and other techniques in tamoxifen-treated patients.
2. Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment.
3. Clomiphene Citrate Effects on Testosterone/Estrogen Ratio in Male Hypogonadism
4. Basal prolactin and the behaviour of the gonadotrophins, testosterone, androstenedione, estradiol, and the sex-hormone-binding globulin during stimulation with clomiphene in subjects with spermatogenic disorders.
5. Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate.
6. Clomiphene in the treatment of adolescent gynecomastia. Clinical and endocrine studies.
7. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study.
8. An investigation of the visual disturbances experienced by patients on clomiphene citrate.

~John Connor
 

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Last edited:
Clomiphene Citrate Effects on Testosterone/Estrogen Ratio in Male Hypogonadism

Ahmad Shabsigh, MD 1 , Young Kang, MD 1 , Ridwan Shabsign, MD 1 , Mark Gonzalez, MD 1 , Gary Liberson, MD 1 , Harry Fisch, MD 1 , and Erik Goluboff, MD 1
1 Department of Urology, NY Presbyterian Medical Center, New York, NY, USA
Correspondence to Harry Fisch, MD, 944 Park Ave, New York, NY 10020, USA. Tel: 212-879-0800; Fax: 212-988-1634; E-mail: harryfisch@aol.com
Copyright Blackwell Publishing Ltd 2005

ABSTRACT

Aim. Symptomatic late-onset hypogonadism is associated not only with a decline in serum testosterone, but also with a rise in serum estradiol. These endocrine changes negatively affect libido, sexual function, mood, behavior, lean body mass, and bone density. Currently, the most common treatment is exogenous testostosterone therapy. This treatment can be associated with skin irritation, gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts. In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone (T) and improving the testosterone/estrogen (T/E) ratio.

Methods. Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospectively. Analysis of baseline and follow-up serum levels of testosterone and estradiol levels were performed.

Results. The mean age was 39 years, and the mean pretreatment testosterone and estrogen levels were 247.6 ± 39.8 ng/dL and 32.3 ± 10.9, respectively. By the first follow-up visit (4???6 weeks), the mean testosterone level rose to 610.0 ± 178.6 ng/dL (P < 0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 (P < 0.001). There were no side effects reported by the patients.

Conclusions. Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estadiol ratio in men with hypogonadism. This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway. Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, and Goluboff E. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med 2005;2:716???721.
 
The Effects of Aging in Normal Men on Bioavailable Testosterone and Luteinizing Hormone Secretion: Response to Clomiphene Citrate*

JOYCE S. TENOVER, ALVIN M. MATSUMOTO, STEPHEN R. PLYMATE and WILLIAM J. BREMNER
Geriatric Research, Education, and Clinical Center and Endocrinology Section, Veterans Administration Medical Center; Population Center for Research in Reproduction; Divisions of Gerontology and Geriatric Medicine and Endocrinology, Department of Medicine, University of Washington School of Medicine Seattle, Washington 98195
Department of Clinical Investigation, Madigan Army Medical Center (S.R.P.) Tacoma, Washington 98431

Address requests for reprints to: Dr. Joyce S. Tenover, Harborview Medical Center (ZA-87), 325 9th Avenue, Seattle, Washington 98104.

Serum testosterone (T) levels in men decline with age while serum LH levels, as measured by RIA, increase. To assess if the decline in serum T levels in healthy aging men is paralleled by an age-related decline in the bioavailable nonsex hormone-binding globulin (SHBG)-bound fraction of T and to determine whether there are age-related changes in LH secretion or LH control of T production, we studied 29 young (aged 22???35 yr) and 26 elderly (aged 65???84 yr) healthy men. All men had single random blood samples drawn, and 14 men in each age group underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Both mean 24-h serum total T levels and non-SHBG-bound T were reduced in elderly men compared to those in young men (P < 0.05), while estradiol and SHBG levels were similar in the 2 age groups. Serum FSH determined by RIA and LH by RIA and bioassay were higher in the elderly men compared to those in young men (P < 0.05), but the ratios of LH bioactivity to immunoreactivity and the LH pulse frequency and amplitude were similar. After CC administration, mean serum total T and non-SHBG-bound levels in young men increased by 100% and 304%, respectively, while in older men these values increased by only 32% and 8%, respectively. However, CC-stimulated LH pulse characteristics and serum levels of estradiol, SHBG, FSH, and bioactive and immunoreactive LH were similar in the 2 groups.

Thus, both at baseline and after CC stimulation, elderly men had significantly lower serum total T and non-SHBG-bound (bioavailable) T levels than did young men, despite similar or increased levels of bioactive LH and similar bioactive to immunoreactive LH ratios and LH pulse characteristics. These results suggest that major age-related changes in the hypothalamicpituitary-testicular axis occur at the level of the testes and are manifested by decreased responsiveness to bioactive LH. Administration of CC to young and elderly men resulted in similar changes in LH pulse characteristics and LH bioactivity and immunoreactivity, suggesting preserved hypothalamic-pituitary responsiveness in the elderly.


* This work supported in part by the V.A., NIH Grant P50-HD-12629, and the Clinical Research Center Facility at the University of Washington, supported by NIH Grant RR-37. Portions of this work have been published in abstract form (Clin Res 34:24A and 430A, 1986; Clin Res 35:402A, 1987).

Received May 4, 1987.
 
Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment.

Ribeiro RS, Abucham J.

Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo, 910. São Paulo 04039-002, Brasil.

CONTEXT: Persistence of hypogonadism is common in male patients with prolactinomas under dopamine agonist (DA) treatment. Conventional therapy with testosterone causes undesirable fluctuations in serum testosterone levels and inhibition of spermatogenesis.

OBJECTIVE: To evaluate the use of clomiphene as a treatment for persistent hypogonadism in males with prolactinomas. DESIGN: Open label, single-arm, prospective trial.

PATIENTS: Fourteen adult hypogonadal males (testosterone <300 ng/dl and low/normal LH) with prolactinomas on DA, including seven with high prolactin (range: 29-1255 microg/l; median: 101 microg/l) despite maximal doses of DA. INTERVENTION: Clomiphene (50 mg/day orally) for 12 weeks. MEASURES: Testosterone, estradiol, LH, FSH, and prolactin were measured before and 10 days, 4, 8, and 12 weeks after clomiphene. Erectile function, sperm analysis, body composition, and metabolic profiles were evaluated before and after clomiphene.

RESULTS: Ten patients (71%), five hyperprolactinemic and two normoprolactinemic, responded to clomiphene (testosterone >300 ng/dl). Testosterone levels increased from 201+/-22 to 457+/-37 ng/dl, 436+/-52, and 440+/-47 ng/dl at 4, 8, and 12 weeks respectively (0.001<P<0.01). Estradiol increased significantly and peaked at 12 weeks. LH increased from 1.7+/-0.4 to 6.2+/-2.0 IU/l, 4.5+/-0.7, and 4.6+/-0.7 IU/l at 4, 8, and 12 weeks respectively (0.001<P<0.05). FSH levels increased in a similar fashion. Prolactin levels remained unchanged. Erectile function improved (P<0.05) and sperm motility increased (P<0.05) in all six patients with asthenospermia before clomiphene.

CONCLUSIONS: Clomiphene restores normal testosterone levels and improves sperm motility in most male patients with prolactinomas and persistent hypogonadism under DA therapy. Recovery of gonadal function by clomiphene is independent of prolactin levels.

PMID: 19359408 [PubMed - indexed for MEDLINE]
 
Basal prolactin and the behaviour of the gonadotrophins, testosterone, androstenedione, estradiol, and the sex-hormone-binding globulin during stimulation with clomiphene in subjects with spermatogenic disorders.

Bolufer P, Rodriguez A, Antonio P, Bosch E, Peiró T.

To clarify the significance of clomiphene test in spermatogenic disorders, it was performed on three groups of subjects: 10 with normozoospermia, 29 with oligozoospermia, and 11 with azoospermia. Two basal blood samples were drawn five days apart; prolactin, FSH, LH, estradiol, testosterone, androstenedione and sex-hormone-binding globulin were determined. 100 mg of clomiphene per day were administered for eleven consecutive days; another sample was drawn on the eleventh day and all the basal parameters, except prolactin, were determined. It may be concluded from the results: a) All the parameters studied increased significantly after clomiphene; and b) Testosterone levels obtained after clomiphene, as well as the increases in this hormone during the test and the ratio delta T/delta LH, were significantly lower in the oligozoospermic group. This finding suggests a decrease in the testicular androgenic function of this group.

PMID: 3937739 [PubMed - indexed for MEDLINE]
 
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.
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.


PMID: 8530597 [PubMed - indexed for MEDLINE]
 
Fertil Steril. 2010 Mar 1;93(4):1169-72. Epub 2009 Jan 9.

An investigation of the visual disturbances experienced by patients on clomiphene citrate.

Racette L, Casson PR, Claman P, Zackon DH, Casson EJ.
The University of Ottawa Eye Institute, Ottawa, Ontario, Canada. lracette@glaucoma.ucsd.edu

Abstract

OBJECTIVE: To evaluate the impact of clomiphene citrate on vision.
DESIGN: Observational study.
SETTING: Patients were referred to the University of Ottawa Eye Institute ophthalmology clinic from the Department of Obstetrics and Gynaecology of the Ottawa Hospital-General Campus.
PATIENT(S): Eight adult females taking clomiphene citrate and experiencing visual disturbances.
INTERVENTION(S): Patients received a comprehensive visual evaluation twice: once during a washout period, and once during an active clomiphene citrate treatment.
MAIN OUTCOME MEASURE(S): Ophthalmologic examination, color vision, visual acuity, contrast sensitivity, visual fields using standard automated perimetry, and foveal flicker sensitivity at high (32 Hz) and low (8 Hz) temporal frequencies.
RESULT(S): We found no differences between the washout and clomiphene citrate conditions for color vision, visual acuity, contrast sensitivity, and visual fields. The only statistically significant difference was found for foveal flicker sensitivity at 32 Hz in the right eye, with a similar trend in the left eye and at 8 Hz in both eyes.
CONCLUSION(S): The effect of clomiphene citrate on vision was minimal, and the visual disturbances were reversible in all patients. A bilateral reduction in flicker sensitivity was the only observed visual disturbance. Women who experience visual symptoms associated with clomiphene citrate should be monitored, but therapy can usually be maintained.


Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

PMID: 19135656 [PubMed - indexed for MEDLINE]
 
Gynecol Obstet Invest. 2010 Dec 16. [Epub ahead of print]

Association between Clomiphene Citrate and Visual Disturbances with Special Emphasis on Central Retinal Vein Occlusion: A Review.

Viola MI, Meyer D, Kruger T.
Department of Obstetrics and Gynecology, Reproductive Medicine Unit, Stellenbosch University and Vincent Pallotti Hospital, Cape Town, South Africa.

Abstract

Objectives: To determine whether clomiphene citrate (CC) can be implicated as a cause for central retinal vein occlusion (CRVO) and other visual disturbances. Methods: For this systematic review, we performed a search of the following databases: PubMed (1976 to November 2009), Medline Plus 2009, Cochrane Library (1996 to November 2009), Google and Google Scholar (1996 to November 2009). Thirty-five relevant titles (25 full papers and 10 abstracts) were identified and read by authors. No review has been published in the literature. The publications included describe adverse effects with clomid and selective estrogen receptor modulators and in particular visual disturbances. The population consisted of infertility patients under ovulation induction with CC. The main outcome measures were loss of vision due to CRVO and other visual changes. Results: CC may predispose to CRVO, but further trials are clearly needed in this area. Conclusion: Physicians should be aware of the potential risk of CC, especially in patients with associated risk factors for CRVO. If visual disturbances occur, therapy should be terminated and the patient referred for specialist ophthalmic care.


Copyright © 2010 S. Karger AG, Basel.

PMID: 21160153 [PubMed - as supplied by publisher]
 
Central retinal vein occlusion secondary to clomiphene treatment in a male carrier of factor V Leiden.

Politou M, Gialeraki A, Merkouri E, Travlou A, Baltatzis S.
Abstract

We report a case of a 35-year-old previously healthy man treated with clomiphene for infertility, who presented with blurred vision in his left eye due to ocular vein occlusion as documented by fluorescein angiography. The patient was heterozygous for the factor V Leiden (FV Leiden) mutation and for the 1298 A-C polymorphism of the methylene-tetrahydrofolate reductase (MTHFR) gene. He was treated with clopidogrel and is now free of symptoms. Because congenital thrombophilia is a moderate risk factor for central retinal vein occlusion and the administration of clomiphene may trigger this process, we recommend screening of young patients for FV Leiden before clomiphene treatment.



PMID: 19371211 [PubMed - indexed for MEDLINE]
 
Am J Dis Child. 1983 Nov;137(11):1080-2.

Clomiphene in the treatment of adolescent gynecomastia. Clinical and endocrine studies.

Plourde PV, Kulin HE, Santner SJ.

Abstract

Twelve boys, aged 12 to 19 years, with persistent gynecomastia were treated with the antiestrogen, clomiphene citrate, at a dose of 50 mg/day by mouth for one to three months. The mean breast size decreased by 0% to 36%, with only five boys experiencing a reduction of greater than 20%. Five boys subsequently required reduction mammoplasty. Levels of urinary gonadotropins, serum testosterone, and estradiol increased significantly during therapy. Since the ratio of testosterone to estradiol remained unchanged during treatment, the antiestrogen effects were achieved primarily at the level of breast tissue. Clomiphene citrate in a dose of 50 mg/day resulted in only small decreases in persistent pubertal gynecomastia and was not a satisfactory medical therapy for the condition.

PMID: 6637910 [PubMed - indexed for MEDLINE]
 
Int Braz J Urol. 2012 Jul-Aug;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. daroscarlos@yahoo.com

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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