Does Testosterone Therapy Protect Against Prostate Cancer?

[Michael Scally MD]

Does Adequate Testosterone Therapy Protect Against Prostate Cancer? Incidence and Severity of Prostate Cancer in Patients Undergoing Prostate Biopsy in a Urological Office
https://endo.confex.com/endo/2016endo/webprogram/Paper25718.html

Background: There are still concerns regarding testosterone therapy (TTh) in middle-aged and elderly men and prostate cancer (PCa).

Methods: Between 2008 and July 2013, 553 prostate biopsies were performed in our office. 22 patients refused biopsy.

We investigated incidence and severity of PCa in three groups:
hypogonadal (T≤350 ng/dl) men receiving TTh,
hypogonadal untreated, and
eugonadal men.

All groups underwent similar screening intensity of at least once per year. Biopsies were performed when indicated according to EAU guidelines.

Results: In 42 hypogonadal men receiving TTh, 7 (16.7%) had a positive biopsy. Of these, 5 had a Gleason score ≤6 (71.4%) and 2 a Gleason score >6 (28.6%). Predominant Gleason score was 3 in all 7 men (100%). Tumor grade was II in 6 (85.7%) and II-III in 1 (14.3%) men.

In 162 untreated hypogonadal men, 84 (51.9%) had a positive biopsy. Of these, 34 had a Gleason score ≤6 (40.5%) and 50 a Gleason score >6 (59.5%). Predominant Gleason score was 3 in 65 (77.4%), 4 in 17 (20.2%) and 5 in 2 (2.4%) men. Tumor grade was II in 35 (41.7%), II-III in 10 (11.9%), III in 34 (40.5%) and IV in 5 (6.0%) men.

In 349 eugonadal men, 132 (37.8%) had a positive biopsy. Of these, 56 had a Gleason score ≤6 (42.4%) and 76 a Gleason score >6 (57.6%). Predominant Gleason score was 3 in 109 (82.6%), 4 in 22 (16.7%) and 5 in 1 (0.1%) men. Tumor grade was II in 59 (44.7%), II-III in 6 (4.5%), III in 63 (47.7%) and IV in 4 (3.0%) men.

Conclusions: The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TTh. The severity of PCa was significantly lower in hypogonadal patients receiving TTh. TTh may protect against high-grade PCa.

 

[master.on]

Is it true that high estrogen is bad for the prostate?
Some pubmed studies show tamoxifen shrinks an enlarged prostate.

 

[Raven101]

Master.on
Can you post a link to those studies that show tomaxifan shrinks an enlarged prostate?

 

[hmccoy99]

interesting information:

Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors.
Anderson FH1, Francis RM, Faulkner K.
Author information

Abstract
This open, prospective therapeutic trial studied the effects of regular moderate androgen supplementation on bone mineral density in eugonadal men with established osteoporosis, and collected data on the safety of androgen therapy used in this setting. 23 men, aged 34-73 years, with vertebral crush fractures and back pain, in whom secondary causes of osteoporosis had been excluded, were treated with fortnightly intramuscular injections of 250 mg testosterone esters (Sustanon 250(R)) for 6 months. Blood pressure was recorded monthly; fasting lipids, glucose, haematocrit, plasma viscosity, and testosterone levels were measured every 3 months. Psychological effects were assessed using the Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), together with questioning on libido changes. Principal outcomes measured were changes in bone mineral density at the hip and spine by dual-energy X-ray absorptiometry (DEXA) over the treatment period. 21 men completed the study period. Mean bone mineral density at the lumbar spine increased from 0.799 g/cm(2) to 0.839 g/cm(2) during treatment (p < 0. 001), a rise of 5% in 6 months. Bone mineral density at the hip did not change. There were significant, favorable changes in diastolic blood pressure (-4.7 mmHg, p < 0.01), serum triglyceride levels (-0.405 mmol/L,p < 0.01), and total cholesterol (-0.27 mmol/L, p < 0.05). Adverse changes included a fall in HDL cholesterol (-0.087 mmol/L, p < 0.05) and a rise in plasma viscosity which was significant at 3 months but not at 6 months. The expected rises in hematocrit (0.434 to 0.456) and FAI (0.504 to 0.887) occurred. We conclude that testosterone supplementation significantly increased bone mineral density in this heterogeneous group of men with idiopathic primary osteoporosis, without an overall adverse effect on cardiovascular risk factors. This treatment warrants further evaluation in a randomized, controlled trial.

 

[hmccoy99]

interesting study:

Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less.
Morgentaler A1, Rhoden EL.
Author information

Abstract
OBJECTIVES:
To determine the prevalence of prostate cancer in hypogonadal men with a prostate-specific antigen (PSA) level of 4.0 ng/mL or less.

METHODS:
A total of 345 consecutive hypogonadal men with a PSA level of 4.0 ng/mL or less underwent evaluation with digital rectal examination and prostate biopsy before initiating a program of testosterone replacement therapy. All men had low serum levels of total or free testosterone, defined as less than 300 and 1.5 ng/dL, respectively.

RESULTS:
Cancer was identified in 15.1%. The cancer detection rate was 5.6%, 17.5%, 26.4%, and 36.4% for a PSA level of 1.0 or less, 1.1 to 2.0, 2.1 to 3.0, and 3.1 to 4.0 ng/mL, respectively (P < 0.05). Cancer was detected in 26 (30.2%) of 86 men with a PSA level of 2.0 to 4.0 ng/mL. Cancer was detected in 21% of men with a testosterone level of 250 ng/dL or less compared with 12% of men with a testosterone level greater than 250 ng/dL (P = 0.04). Men with free testosterone levels of 1.0 ng/dL or less had a cancer rate of 20% compared with 12% for men with greater values (P = 0.04). The odds ratio of cancer detection for men in the lowest tertile compared with the highest tertile was 2.15 (95% confidence interval 1.01 to 4.55) for total testosterone and 2.26 (95% confidence interval 1.07 to 4.78) for free testosterone.

CONCLUSIONS:
Prostate cancer was present in more than 1 of 7 hypogonadal men with PSA of 4.0 ng/mL or less. An increased risk of prostate cancer was associated with more severe reductions in testosterone.

 

[hmccoy99]

Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia.
Rhoden EL1, Morgentaler A.
Author information

Abstract
PURPOSE:
One of the greatest concerns among clinicians regarding testosterone replacement therapy (TRT) is the fear of causing or promoting prostate cancer. We evaluated prostatic changes in hypogonadal men with and without high grade prostatic intraepithelial neoplasia (PIN), which is considered a prostatic precancerous lesion, after 1 year of TRT.

MATERIALS AND METHODS:
A total of 75 hypogonadal who completed 12 months of TRT were studied. All underwent prostate biopsy prior to initiating treatment. Of the men 55 had benign prostate biopsies (PIN-) and 20 had PIN without frank cancer (PIN+). All men with PIN underwent repeat biopsy to exclude cancer prior to the initiation of testosterone treatment. Prostate specific antigen (PSA), and total and free testosterone were determined prior to treatment and at 1 year. Repeat biopsy was performed for a change noted on digital rectal examination or for a PSA increase of 1 ng/l or greater.

RESULTS:
PSA was similar at baseline in men with and without PIN (1.49 +/- 1.1 and 1.53 +/- 1.6 ng/dl, p >0.05) and after 12 months of TRT (1.82 +/- 1.1 and 1.78 +/- 1.6 ng/dl, respectively, p >0.05). A slight, similar increase in mean PSA was noted in the PIN- and PIN+ groups (0.25 +/- 0.6 and 0.33 +/- 0.6 ng/dl, p >0.05). One man in the PIN+ group had cancer after biopsy was performed due to abnormal digital rectal examination. Four additional men in the PIN- group and 2 in the PIN+ group underwent re-biopsy for elevated PSA and none had cancer. No differences were noted between the PIN- and PIN+ groups with regard to total and free testosterone at baseline and at 1 year (p = 0.267).

CONCLUSIONS:
After 1 year of TRT men with PIN do not have a greater increase in PSA or a significantly increased risk of cancer than men without PIN. These results indicate that TRT is not contraindicated in men with a history of PIN.


NOTE:

Prostatic intraepithelial neoplasia (PIN) is a condition “defined byneoplastic growth of epithelial cells within preexisting benign prostaticacini or ducts.” 3. Because PIN satisfies almost all the requirements for a premalignant condition, high-grade PIN (HGPIN) is widely accepted as a precursor to prostate cancer.

 

[hmccoy99]

Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism.
Shabsigh A1, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, Goluboff E.
Author information

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 testosterone 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/estradiol ratio in men with hypogonadism. This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway.

Clomid helps

henry

 

[hmccoy99]

The Role of Estrogens in Prostate Carcinogenesis: A Rationale for Chemoprevention
Maarten C Bosland, DVSc, PhD
Author information ► Copyright and License information ►

This article has been cited by other articles in PMC.

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Abstract

Summary and Conclusions
Estrogens and ERs are clearly linked to the development and progression of prostate cancer. These activities of estrogens might be associated not only with their ER-mediated effects but also with the DNA-damaging and potentially mutagenic activity of some estrogenic compounds. ERmediated activity of estrogens that are carcinogenic to the prostate in animal models provides a rationale for the exploration of using antiestrogens that block the ER as preventive agents. The results of one clinical trial suggest that this is a realistic proposition. In addition, there is some evidence to suggest that antiestrogens can have therapeutic benefit as well, but this has not yet been explored clinically. Because chemoprevention of prostate cancer should target not only the development and progression of HGPIN but also histologic prostate cancer, discovering drugs or natural substances that interfere with the development of both HGPIN and cancer and progression of HGPIN to cancer will be very important. Because prostate carcinogenesis involves androgens and oxidative stress, which are associated with inflammation and possibly estrogen effects, mixed antiestrogenic, anti-androgenic, and antioxidant activities of agents or combinations of agents are probably critical to the success of chemoprevention of prostate cancer. Successful agents must also be very safe because of the very long duration of their application in men at risk for prostate cancer. Thus, SERMs offer the possibility of prevention and/or treatment of prostate cancer. Several approaches to prostate cancer chemoprevention and treatment are under development.

Main Points

• Observations from several studies led to the hypothesis that increased circulating estrogens might elevate prostate cancer risk and act through the estrogen receptor; this idea is strongly supported by the finding that estrogens enhance androgen-induced prostate cancer in an animal model.
• Evidence from animal studies suggests that estrogens can have genotoxic activity in the rat prostate and that this might be related to induction of cancer by estradiol plus testosterone; there are at present no human data in this regard.
• Experimental observations suggest that antiestrogens might have therapeutic or preventive efficacy in prostate cancer. Studies with tamoxifen do not support the concept of therapeutic benefit, but there are no completed human studies exploring this idea with other agents. There is some support from a human study for the notion that antiestrogens might have preventive efficacy against prostate cancer.

henry