Finasteride [5ARI] Induced/Associated Effects

[Michael Scally MD]

I do not have the full-text, yet! The title sure got my attention.


Berthold D, Lhermitte B, Uffer M, Doerfler A. Finasteride-related Leydig cell tumour: report of a case and literature review. Andrologia. Finasteride-related Leydig cell tumour: report of a case and literature review - Berthold - 2011 - Andrologia - Wiley Online Library

Leydig cell tumours (LCTs) of the testis are rare. Their origin is still unknown. This case report describes a potential relationship between LCT and prolonged exposure to Finasteride.

 

[Structure]

I do not have the full-text, yet! The title sure got my attention.


Berthold D, Lhermitte B, Uffer M, Doerfler A. Finasteride-related Leydig cell tumour: report of a case and literature review. Andrologia. Finasteride-related Leydig cell tumour: report of a case and literature review - Berthold - 2011 - Andrologia - Wiley Online Library

Leydig cell tumours (LCTs) of the testis are rare. Their origin is still unknown. This case report describes a potential relationship between LCT and prolonged exposure to Finasteride.

It's a short article. Here's the full text:

Case report

A 36-year-old man presented to his general practitioner with right testicular pain that had started 4 days ago. Physical examination revealed mild gynaecomastia, and an ultrasound of the testis was performed. On the right testis, a small, hypervascularised lesion was detected and a suspicious, well-circumscribed lesion of 1 cm was described. The lesion appeared to be homogenous and the radiologist adopted, as its first diagnosis, a possible seminoma. The chest–abdomen–pelvis CT scan did not show any further lesions. LDH, a-foetoprotein and b-HCG were within normal range. Medical history was positive for alopecia treated with Finasteride 1 mg per daily from age 26 to 34. The treatment was stopped 1 year before due to painful gynaecomastia. After discontinuation of Finasteride, the breast hypersensitivity improved while the hypertrophia persisted. He is married, father of two children, conceived while taking Finasteride, and he never experienced sexual dysfunction. He has no family history of cancers. After diagnosis, the patient underwent right inguinal orchidectomy without complications. The pathology revealed a well-circumscribed tumour measuring 1.2 cm. The tumour cells were of moderate size, with abundant cytoplasm and central round nuclei with a prominent nucleolus. The immunoprofile was compatible with a Leydig cell tumours (LCT) with expression of inhibin and calretinin. There was no mitosis, necrosis or vascular invasion. The remnant testicular parenchyma was normal with a preserved spermatogenesis and absence of Leydig cells hyperplasia (Fig. 1).

Discussion

Leydig cell tumours are very rare neoplasms, representing 1–3% of testicular tumours. They arise from the interstitial cells, located between the seminiferous tubules and produce testosterone in response to luteinising hormone (Al-Agha & Axiotis, 2007). They are frequently hormonally active. In some cases, the tumour presents bilaterally, synchronously or metachronously. The vast majority of LCTs are benign; some cases of malignant behaviour have been described, usually showing pathologic features such as vascular invasion, necrosis, enhanced mitosis or large tumour size. LCTs can occur at any age, but they are common in prepubertal boys (most often between 5 and 10 years of age) and in men aged 30–60 years. Finasteride is a selective inhibitor of the enzyme 5-alpha reductase. This intracellular enzyme is responsible for conversion of testosterone to dihydrotestosterone (DHT). The inhibition of 5-alpha reductase in men results in a decrease level of DHT in the circulation, as well as in the prostate. Because DHT is a tropic hormone for the prostate, Finasteride is indicated for the treatment of benign prostatic hyperplasia in man. Dihydrotestosterone is also a major androgen responsible for the progressive miniaturisation of the scalp hair follicles and subsequent visible hair thinning. Finasteride is registered for the prevention of hair loss with dosage of 1 mg day)1 continuously (Kaufman et al., 2008). Mice treated with Finasteride at higher doses (‡25 mg kg)1 day)1 for 83 weeks) developed testicular Leydig cell hyperplasia and Leydig adenomas (Prahalada et al., 1994). The mechanism by which Finasteride causes proliferative changes in the testis is not known. It is likely that the block of the negative feedback of testosterone to the hypothalamic-pituitary axis resulting in increased serum LH levels leading to an increased incidence of Leydig cell hyperplasia and adenomas (Prentice & Meikle, 1995). The appearance of gynaecomastia in patients treated with Finasteride suggests that an increased level of oestrogens has also an influence on this particular side effect. Whether increased oestrogens may have played a role in the incidence of LCT in our patient remains speculative. Finasteride is a frequently used and well-studied drug, for example in the prostate cancer prevention study (Thompson et al., 2003), Finasteride was given for 7 years to 4300 men (but only two-thirds of the patients were compliant) and no single case of Leydig cell tumour was described. However, patients treated for prostate hyperplasia or prostate cancer prevention are typically elder than our patient who started at the age of 26 and was exposed for 8 years to the drug. The fact that he developed gynaecomastia speaks in favour of a biologically very active drug.

Conclusion

We believe in a possible relationship between Finasteride and LCT. Further reports and research will help confirm such a relationship.

 

[Michael Scally MD]

The Effects of Chronic 5-Alpha Reductase Inhibitor Treatment on Erectile Function

Benign prostatic hyperplasia (BPH) is prevalent among middle-aged and elderly men, affecting as many as 75% of men over 50 years old. 5-alpha-reductase inhibitors (5ARIs) are frequently used in the treatment of BPH, and may cause sexual dysfunction. While the rate of erectile dysfunction (ED) in clinical trials with 5ARIs has been reported to vary from 5 to 9%, it is still a difficult clinical issue that physicians must deal with. ED, or any sexual dysfunction for that matter, can have dramatic effects on a man`s quality of life, self-esteem, and ability to maintain intimate relationships.

There are two isoforms of 5-alpha reductase, type-1 and type- 2. Dutasteride (Avodart, Glaxo Smith Kline, Philadelphia, PA, USA), is one of the two oral 5ARIs in clinical use for the treatment of men with BPH. This agent suppresses both isoenzymes and diminishes circulating dihydrotestosterone (DHT) by more than 90%. In clinical trials, 5ARIs have been associated with an increased incidence of ED, ejaculatory dysfunction (EjD), and decreased libido. The initial clinical report on the potency of dutasteride established adverse sexual side effect rates of 7.3% for ED, 4.2% for diminished libido, and 2.2% for EjD.

Nitric oxide (NO) and its synthetic enzyme NO synthase (NOS), are major mediators of erectile function. Androgens increase NOS expression in the penile corpus cavernosum of rats, and DHT is much more effective at increasing NOS expression than testosterone. The deleterious effect of dutasteride on sexual and erectile function is perhaps linked to the reduction in DHT associated with its use, thereby decreasing levels of NO and NOS in the corpus cavernosum.

Though a number of clinical trials have linked 5ARIs and sexual dysfunction, there has been little investigation into the mechanisms of the sexual side effects related to use of these medications. Given the lack of available preclinical data, the goal of this study was to investigate the mechanisms of these recognized side effects by assessing different parameters of erectile function in 5ARI-treated rats. Further elucidation of the processes involved may develop new strategies for the prevention and treatment of ED in clinical practice.

Since the introduction of 5ARIs in clinical trials, men have experienced sexual side effects during their use. Despite the reported effects, few have studied the mechanisms underlying this challenge faced by patients and their physicians. NOS expression and NO responses are crucial to penile erection. DHT is potent in increasing NOS expression; hence DHT reduction by 5ARIs would impair the NO relaxant pathway that facilitates erection. 5ARIs not only affect different subtypes of NOS in different ways, but also have effects on molecular components in all erectile pathways. Further molecular studies in human models are warranted to help protect patients from the recognized sexual side effects experienced with current medical therapies for BPH.


Pinsky MR, Gur S, Tracey AJ, Harbin A, Hellstrom WJG. The Effects of Chronic 5-Alpha-Reductase Inhibitor (Dutasteride) Treatment on Rat Erectile Function. The Journal of Sexual Medicine. The Effects of Chronic 5-Alpha-Reductase Inhibitor (Dutasteride) Treatment on Rat Erectile Function - Pinsky - 2011 - The Journal of Sexual Medicine - Wiley Online Library

Introduction. Numerous clinical series have reported an association between 5-alpha-reductase inhibitors (5ARIs) and sexual dysfunction, but there are limited preclinical data available.

Aim. To further investigate the mechanisms of erectile dysfunction (ED) related to 5ARI therapy using a rat model.

Main Outcome Measures. Outcome measures include serum dihydrotestosterone (DHT), relaxant and contractile properties of cavernosal muscle, and nitric oxide synthase expression.

Methods. Twenty adult male Sprague-Dawley rats were randomized into control (N = 10) and dutasteride (0.5 mg/rat/day, in drinking water, N = 10) groups. Serum samples were obtained at baseline, from which DHT was measured after 30 days of treatment via radioimmunoassay (Beckman Coulter, Fullerton, CA, USA). Before the terminal blood draw, erectile response was measured using cavernosal nerve stimulation. The relaxant and contractile properties of cavernosal muscle strips were evaluated in tissue baths, and immunohistochemical (IHC) staining for nitric oxide synthase (NOS) and collagen deposition was performed.

Results. Mean serum DHT was suppressed by 86.5% (range 64.2–94.8%) after 30 days of 5ARI treatment and was statistically significant (P = 0.0024). In vivo erectile response in the dutasteride treated group decreased significantly compared with control (P < 0.001). While electrical field stimulation (EFS)-induced and acetylcholine-induced relaxation was decreased, EFS-induced and phenlyephrine-induced adrenergic contraction was significantly enhanced in the dutasteride group (P < 0.01). IHC studies demonstrated increased collagen deposition in the treatment arm as well as altered expression of neuronal NOS (nNOS) and inducible NOS (iNOS).

Conclusions. The 5ARIs, as demonstrated in these rat cavernosal smooth muscle studies, have a detrimental effect on erectile function. Enhanced iNOS expression may protect penile smooth muscle from fibrosis. The effect of 5ARIs on human sexual function warrants further investigation.

 

[Michael Scally MD]

Merck’s Baldness Drug Linked to Sex Concerns After Use
Merck’s Baldness Drug Linked to Sex Concerns After Use - Businessweek

By Anna Edney on April 12, 2012

Merck & Co. (MRK) (MRK)’s baldness drug Propecia and enlarged prostate therapy Proscar will carry labels linking them to sexual dysfunction after the treatments are no longer used, U.S. regulators said.

Propecia’s packaging will include warnings about libido, orgasm and ejaculation disorders that occur after patients stop using the medicines, the Food and Drug Administration said yesterday in a statement. Proscar’s similar warning is limited to decreased libido, and both drugs will include on their labels reports of infertility and poor semen quality that normalized when people stopped using the drugs, the agency said.

“Despite the fact that clear causal links between finasteride (Propecia and Proscar) and sexual adverse events have not been established, the cases suggest a broader range of adverse effects than previously reported in patients taking these drugs,” the FDA said in its statement.

Pamela Eisele, a spokeswoman for Merck, didn’t respond to telephone calls and an e-mail seeking comment on the label revision.

The FDA reviewed 421 reports of sexual dysfunction from 1998 to 2011 related to Propecia. Of these, 59 cases reported the condition lasted longer than three months after drug discontinuation. The agency reviewed 131 cases of erectile dysfunction and 68 cases of decreased libido with Proscar from 1992 to 2010.

 

[hardasnails1973]

Merck’s Baldness Drug Linked to Sex Concerns After Use
Merck’s Baldness Drug Linked to Sex Concerns After Use - Businessweek

By Anna Edney on April 12, 2012

Merck & Co. (MRK) (MRK)’s baldness drug Propecia and enlarged prostate therapy Proscar will carry labels linking them to sexual dysfunction after the treatments are no longer used, U.S. regulators said.

Propecia’s packaging will include warnings about libido, orgasm and ejaculation disorders that occur after patients stop using the medicines, the Food and Drug Administration said yesterday in a statement. Proscar’s similar warning is limited to decreased libido, and both drugs will include on their labels reports of infertility and poor semen quality that normalized when people stopped using the drugs, the agency said.

“Despite the fact that clear causal links between finasteride (Propecia and Proscar) and sexual adverse events have not been established, the cases suggest a broader range of adverse effects than previously reported in patients taking these drugs,” the FDA said in its statement.

Pamela Eisele, a spokeswoman for Merck, didn’t respond to telephone calls and an e-mail seeking comment on the label revision.

The FDA reviewed 421 reports of sexual dysfunction from 1998 to 2011 related to Propecia. Of these, 59 cases reported the condition lasted longer than three months after drug discontinuation. The agency reviewed 131 cases of erectile dysfunction and 68 cases of decreased libido with Proscar from 1992 to 2010.

Isn't it amazing they knew about this how many years ago and never once mentioned it on the insert. ...

 

[Michael Scally MD]

Questions and Answers: Finasteride Label Changes
http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm299754.htm

On April 11, 2012, the U.S. Food and Drug Administration (FDA) announced changes to the professional labels for Propecia (finasteride 1 mg) and Proscar (finasteride 5 mg) to expand the list of sexual adverse events reported to FDA as some of these events have been reported to continue after the drug is no longer being used (note that erectile dysfunction after stopping use of these drugs was added as a known event in 2011). The new label changes include:

• A revision to the Propecia label to include libido disorders, ejaculation disorders, and orgasm disorders that continued after discontinuation of the drug.

• A revision to the Proscar label to include decreased libido that continued after discontinuation of the drug.

• A revision to both the Propecia and Proscar labels to include a description of reports of male infertility and/or poor semen quality that normalized or improved after drug discontinuation.

Despite the fact that clear causal links between finasteride (Propecia and Proscar) and sexual adverse events have NOT been established, the cases suggest a broader range of adverse effects than previously reported in patients taking these drugs. Information about these adverse events may be important to individual patients. Therefore, prescribers and patients need to be aware of them, as part of a discussion of risk and benefits of finasteride when determining the best treatment options.

Below are some additional questions and answers on this announcement and action.

Q1. What are Proscar and Propecia?

A1. Proscar and Propecia both contain the active ingredient finasteride and belong to a class of prescription medicines called 5 alpha-reductase inhibitors.

Proscar (finasteride 5 mg) was approved by FDA in 1992 and is indicated for the treatment of bothersome symptoms in men with benign prostatic hyperplasia (also referred to as BPH or an enlarged prostate). Proscar is also approved to reduce the risk of urinary retention or the need for surgery related to BPH.

Propecia (finasteride 1 mg) was approved by FDA in 1997 for use in males only and is indicated for the treatment of male pattern hair loss.

Q2. Are any similar side effects already listed in the labels of Proscar and Propecia?

A2. Yes. Sexual side effects were reported by patients during clinical trials, and this information was included in the Proscar and Propecia’s labels at the time of approval in 1992 and 1997, respectively. In controlled clinical trials, these side effects resolved in patients who stopped finasteride, as well as in most patients who continued therapy. In 2011, both Proscar and Propecia’s labels were revised to include erectile dysfunction that continued after drug discontinuation.

Q3. What studies and/or reports did FDA review to determine this information should be included in the label?

A3. For Propecia, FDA reviewed 421 postmarketing reports of sexual dysfunction submitted to the Agency’s Adverse Events Reporting System (AERS) database between 1998 and 2011. Of these, 59 cases reported sexual dysfunction that lasted for at least three months following discontinuation of Propecia, and included erectile dysfunction, decreased libido, problems with ejaculation and orgasm disorders.

For Proscar, FDA reviewed 131 cases of erectile dysfunction and 68 cases of decreased libido associated with the use of finasteride 5 mg submitted to the drug sponsor’s worldwide safety database between 1992 and 2010. Where information was available, these reported events of erectile dysfunction and decreased libido lasted for at least several weeks after drug discontinuation.

Regarding semen quality, 251 cases associated with Propecia use were identified from the sponsor’s safety database. Of these cases, 13 contained enough information for FDA to evaluate. FDA reviewed 29 cases associated with Proscar use, of which only 3 cases involved men with benign prostatic hypertrophy. There was limited information available on these cases to assess the effect of finasteride on semen quality.

FDA also requested additional information from the drug sponsor to assess the reports. No new clinical studies were reviewed to evaluate these adverse events. FDA is not aware of any additional controlled clinical studies conducted to evaluate these adverse events or to determine their cause or duration.

Q4. Why are the label changes for Proscar and Propecia different?

A4. The labels reflect the differences in the population of men using Propecia and Proscar, which have different indications of use. Postmarketing cases of sexual dysfunction that continued after patients stopped using Propecia occurred in a younger population of men compared to cases reported with Proscar. Older men who reported sexual adverse events with Proscar, in general, also had concurrent medical conditions and were treated with medications that may affect sexual function.

Q5. Do all men experience sexual adverse events when using Propecia or Proscar?

A5. No. Only a small percentage of men using these drugs have experienced a sexual adverse event. The frequency of sexual adverse events is best obtained from controlled clinical trials. Analysis of these controlled clinical trials showed that during treatment with Propecia, 36 (3.8%) of 945 men had reported one or more adverse sexual experiences as compared to 20 (2.1%) of 934 men who did not receive Propecia (received placebo).

Sexual adverse events associated with Proscar use were identified in two clinical trials. This information is included in the Proscar label. In one trial, these events were reported more frequently during the first year of treatment with Proscar as compared to men who received placebo. In years 2-4 of the trial, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder.

Q6. Has FDA notified healthcare professionals about the risk of sexual adverse events associated with finasteride use?

A6. FDA has notified healthcare professionals who would normally prescribe finasteride products—dermatologists, family practice professionals, internists and urologists—about FDA’s review of postmarketing reports and the label changes. This communication informs prescribers that FDA has not established a cause and effect relationship between finasteride and the sexual adverse events that continued after stopping drug use.

Q7. I am currently taking Propecia or Proscar. What should I do?

A7. If you have questions or concerns, you should consult your health care provider to discuss the risks and benefits of the medication as they specifically apply to you. Do not stop taking your medication without first consulting with your health care provider.

FDA believes that finasteride remains a safe and effective drug for its approved indications. Healthcare professionals and patients should consider this new label information when deciding the best treatment option.

Q8. How do I report an adverse event to the FDA?

A8. Patients and healthcare professionals should report adverse events experienced with Proscar or Propecia to the FDA MedWatch program. You can reach MedWatch at 1-800-332-1088, report online at MedWatch Online, or submit your report using regular mail and postage-paid FDA Form 3500.

 

[Michael Scally MD]

Irwig MS. Persistent Sexual Side Effects of Finasteride: Could They Be Permanent? The Journal of Sexual Medicine. Persistent Sexual Side Effects of Finasteride: Could They Be Permanent? - Irwig - 2012 - The Journal of Sexual Medicine - Wiley Online Library

Introduction.? Finasteride has been associated with sexual side effects that may persist despite discontinuation of the medication. In a clinical series, 20% of subjects with male pattern hair loss reported persistent sexual dysfunction for ?6 years, suggesting the possibility that the dysfunction may be permanent. These subjects also reported a wide range of symptoms including changes in cognition, ejaculate quality, and genital sensation. Other medications have been associated with irreversible neurological effects, such as phenothiazines with tardive dyskinesias.

Aim.? To prospectively study whether the persistent sexual side effects associated with finasteride resolve or endure over time.

Methods.? Subjects (N = 54) with persistent sexual side effects associated with finasteride were reassessed after 9–16 months (mean 14 months). All subjects were otherwise healthy young men without any baseline sexual dysfunction, medical conditions, psychiatric conditions, or use of oral prescription medications prior to taking finasteride for male pattern hair loss.

Main Outcome Measure.? Scores from the Arizona Sexual Experience Scale (ASEX).

Results.? The participation rate was 81%. At reassessment persistent sexual side effects continued to be present in 96% of subjects. According to the ASEX scores, 89% of subjects met the definition of sexual dysfunction. Neither the length of finasteride use nor the duration of the sexual side effects correlated to changes in scores of sexual dysfunction.

Conclusion.? In most men who developed persistent sexual side effects (?3 months) despite the discontinuation of finasteride, the sexual dysfunction continued for many months or years. Although several rat studies have shown detrimental changes to erectile function caused by 5 alpha reductase inhibitors, the persistent nature of these changes is an area of active research. Prescribers of finasteride and men contemplating its use should be made aware of the potential adverse medication effects.

 

[Deadballs]

At least we are now getting proof that we are not insane as well as sexually repressed. I've been 3 years off now approx and still no change in sexual desire. I'm 1/10th of the man I used to be.

The only thing that ever made me feel normal again was 25mg of proviron daily but this only worked for 3 days then stopped working completely. Tripling the dosage made no difference either!

Does anyone know if I used HCG along with proviron I could keep the libido effects that it gave me? Even if I only used it 2 days a week or something like that. I'd like to be able to enjoy sex just twice a week would be a blessing!

 

[Michael Scally MD]

Software engineer claims generic version of Propecia turned him into a woman
Software engineer says generic version of Propecia baldness drug turned him into a woman - NYPOST.com

 

[Michael Scally MD]

Irwig MS. Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride With Persistent Sexual Side Effects. Journal of Clinical Psychiatry, 2012. http://article.psychiatrist.com/dao_1-login.asp?ID=10007988&RSID=31923221437757

Objective: Finasteride, a commonly prescribed medication for male pattern hair loss, has recently been associated with persistent sexual side effects. In addition, depression has recently been added to the product labeling of Propecia (finasteride 1 mg). Finasteride reduces the levels of several neuroactive steroids linked to sexual function and depression. This study assesses depressive symptoms and suicidal thoughts in former users of finasteride who developed persistent sexual side effects despite the discontinuation of finasteride.

Method: In 2010–2011, former users of finasteride (n = 61) with persistent sexual side effects for ? 3 months were administered standardized interviews that gathered demographic information, medical and psychiatric histories, and information on medication use, sexual function, and alcohol consumption. All former users were otherwise healthy men with no baseline sexual dysfunction, chronic medical conditions, current or past psychiatric conditions, or use of oral prescription medications before or during finasteride use. A control group of men (n = 29), recruited from the community, had male pattern hair loss but had never used finasteride and denied any history of psychiatric conditions or use of psychiatric medications. The primary outcomes were the prevalence of depressive symptoms and the prevalence of suicidal thoughts as determined by the Beck Depression Inventory II (BDI-II); all subjects self-administered this questionnaire at the time of the interview or up to 10 months later.

Results: Rates of depressive symptoms (BDI-II score ? 14) were significantly higher in the former finasteride users (75%; 46/61) as compared to the controls (10%; 3/29) (P < .0001). Moderate or severe depressive symptoms (BDI-II score ? 20) were present in 64% (39/61) of the finasteride group and 0% of the controls. Suicidal thoughts were present in 44% (27/61) of the former finasteride users and in 3% (1/29) of the controls (P < .0001).

Conclusions: Clinicians and potential users of finasteride should be aware of the potential risk of depressive symptoms and suicidal thoughts. The preliminary findings of this study warrant further research with controlled studies.

 

[dyna5]

i wonder if sexual effects could be substantially reduced is only .05 - 1mg was only taken 3x per week opposed to every day?

 

[Dr JIM]

The dosage was determined based on efficacy! If ya mess with that ya screw up its effectiveness, in all probability.

 

[JanSz]

i wonder if sexual effects could be substantially reduced is only .05 - 1mg was only taken 3x per week opposed to every day?

I am assuming that some men are affected by Fina and duo-steride by really unknown reasons.
I am assuming that most affected men got there because they inhibited elements in Steroid Hormone Panel so much that they are beyond body's ability to restore their levels, once men stops taking this medicine.

I am assuming that man who would monitor levels of their steroid hormones,
and use Fina or Duo only when having high levels of steroid metabolites,
would have better chance at escaping side effects.

Finasteride, Propecia, Proscar are 5aR inhibitors
Duosteride, Avodart is 5aR and 5bR inhibitor

5aR is involved in in metabolizing
cortisol---->5a-THF
Androstenedione------>Androsterone
Testosterone--->5aDHT

5bR is involved in metabolizing
Testosterone----->5b-DHT

All above metabolites can be tested using 24hr urine, at
Meridian Valey Laboratory
owned by dr Johnathan Wright.

I do not know of any other this type test. Someone please post if it exist somewhere.
Rhein Labs or Genova Labs are always missing some important metabolites.

Significant shortcut, but still probably highly helpful, would be to test
DHT, serum
and
5?-Androstane-3?, serum
available at LabCorp

Use Fina or Duo only when the two metabolites are over the range.

...

 

[xeno]

New idea.

Many endocrine diseases involve antibodies to enzymes/hormones/receptors. In my uneducated opinion the 'post-finasteride syndrome' is an autoimmune condition against 5aR/DHT/ARs caused by a reaction to Finasteride (a synthetic androgen).

Antibodies to Testosterone can cause hypogonadism; http://jcem.endojournals.org/content/83/1/14.full.pdf
An autoimmune reaction to ARs is known in vivo, and has been proposed as a treatment for prostate cancer; CD8+ T cells specific for the andr... [Cancer Immunol Immunother. 2011] - PubMed - NCBI
Anti-5aR and anti-AR antibodies are known to exist in vivo too. Autoimmune anti-androgen-receptor a... [Proc Natl Acad Sci U S A. 1985] - PubMed - NCBI Anti-5 alpha-reductase autoantibodie... [J Clin Endocrinol Metab. 1990] - PubMed - NCBI
(Note that antibodies can have antagonist effects at a hormone receptor as well as agonist or blocking effects, see; Treatment of Type B Insulin Resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies )

This explains the rarity of side effects. The persistence of side effects. Why TRT does not work. The range of severity. Why the side effects can get worse after stopping. It also explains some of the more unexpected side effects, numbness (due to a reaction to 5ar2) and muscle loss (effecting true bioavailable T).

Dont if some or all of 5aR/DHT/AR would be involved here, but its certainly worth looking into.

 

[bballer100]

If autoantibodies are indeed being produced, that is truly worrying. If it is only to the 5 alpha reductase enzyme, then the administration of exogenous DHT like compunds (Proviron) may help to alleviate the symptoms. But if it is to the receptor, I don't know if there is any treatment available that can help. Weirdly, I experienced the endocrine crash after experiencing prostate hyperplasia like issues (burning while urinating, sensation of constantly having to urinate but nothing comes out). The paper says that autoantibodies were produced in men with prostate cancer; so I wonder if there is a correlation. How would one even test for whether these antiautobodies are being made?

 

[Dr JIM]

Most often self diagnosis begets the wrong diagnosis !!!!

 

[ViaSwiss]

I encourage you guys to donate to the research looking for a cause/cure.

PFSfoundation.com

 

[Michael Scally MD]

Mysore V. Finasteride and sexual side effects. Indian Dermatol Online J 2012;3(1):62-5. http://www.idoj.in/temp/IndianDermatolOnlineJ3162-2973953_081539.pdf

Finasteride, a 5-alpha reductase inhibitor, widely used in the medical management of male pattern hairloss, has been reported to cause sexual side effects. This article critically examines the evidence available and makes recommendations as to how a physician should counsel a patient while prescribing the drug.

 

[Michael Scally MD]

Motofei IG, Rowland DL, Georgescu SR, et al. A pilot study on the sexual side effects of finasteride as related to hand preference for men undergoing treatment of male pattern baldness. BJU Int. A pilot study on the sexual side effects of finasteride as related to hand preference for men undergoing treatment of male pattern baldness - Motofei - 2012 - BJU International - Wiley Online Library

What's known on the subject? and What does the study add?

Cerebral lateralization/specialization is a neurophysiological feature that has been documented regarding somatic, psychological and sexual functioning and that may be manifested in differences in hand preference, cognitive style, gonadal hormonal effects and possibly even sexual orientation. In this study we investigated a possible cerebral lateralization effect on sexual response for dihydrotestosterone, using finasteride as a hormone-blocking compound.

The results of this study differ substantially from other studies examining the effects of finasteride on sexual response, presumably due to the greater restrictions we placed on defining relevant sexual activity, to our alerting patients to both positive and negative sexual effects and to the fact that we assessed the effects separately in right-handed vs left-handed patients. Handedness, as a proxy for cognitive style and possible lateralization of effect/function, appears to be a relevant factor when considering the sexual effects of specific gonadal hormones.

OBJECTIVE
?• To investigate the relationships between pharmacologically induced deprivation of dihydrotestosterone, sexual arousal, libido and hand preference, by comparing the self-reported sexual response prior to and during reception of the anti-androgen finasteride in men undergoing treatment for male pattern baldness.

PATIENTS AND METHOD
?• In total, 33 sexually healthy Romanian men participated in this study.
?• Patients prospectively provided information regarding their sexual functioning (over 4 weeks), as measured by the International Index of Erectile Function (IIEF) prior to and after commencing treatment with 1 mg finasteride for male pattern baldness.

RESULTS
?• Overall IIEF scores as well as the erectile function, orgasmic function, sexual desire and overall satisfaction subscales showed group, treatment and group by treatment effects.
?• The intercourse satisfaction subscale showed group and group by treatment effects.
?• On most subscales, right-handed men showed no effect or lower sexual function whereas left-handed men reported no effect or improved sexual function, primarily.

CONCLUSIONS
?• These results suggest that the sexual effects of dihydrotestosterone deprivation may depend on handedness – a proxy variable that may represent cognitive style – which lends further support to the idea of two distinct neuroendocrine psychosexual axes.
?• They further suggest that detection of such sexual effects may be enhanced by using research methodologies and communication strategies that increase patients' sensitization to such effects.

 

[Michael Scally MD]

Gur S, Kadowitz PJ, Hellstrom WJ. Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin Drug Saf. An Error Occurred Setting Your User Cookie

Introduction: Treatment with 5-alpha reductase inhibitors (5ARI) is commonly utilized for the treatment of benign prostatic hyperplasia (BPH). The true prevalence of sexual side effects with 5ARI treatment is currently unknown.

Areas covered: The current article reviews the reported adverse effects of 5ARI in regard to erectile function, sexual desire and ejaculation. A PubMed search was performed of all articles from 1990 to present, which reported any sexual side effects with finasteride or dutasteride. Preference was given to more recent and human studies where available.

Expert opinion: Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.