Cyproterone acetate is a synthetic steroidal antiandrogen drug used to treat prostate cancer. It suppresses androgen hormones by inhibiting growth of testosterone-sensitive cells. An acetate salt, the drug works by binding to androgen receptors to prevent receptor activation. Additionally, this drug reduces luteinizing hormone via the pituitary gland, which reduces androgen secretion in the testes and overall serum testosterone levels. It has weak progestational and antineoplastic activities. It has been studied for its effect in reducing hot flashes in patients with cancer.
A systematic review of the literature of hot flash interventions for men treated for prostate cancer found that some hormonal agents, including cyproterone acetate, were able to decrease hot flashes by at least 75% but produced severe side effects. All studies were too limited to evaluate safety and long-term risks of treatment.
Effectiveness Not Established
Frisk, J. (2010). Managing hot flushes in men after prostate cancer--a systematic review. Maturitas, 65(1), 15-22.doi:10.1016/j.maturitas.2009.10.017
To describe hot flushes in men with prostate cancer and their treatment methods.
TYPE OF STUDY Systematic review
DATABASES MEDLINE, ISI Web of Knowledge, Cinahl & PsycINFO
KEYWORDS Prostate cancer, androgen deprivation therapy, vasomotor symptoms, hot flashes treatment
INCLUSION CRITERIA All studies were randomized controlled studies (RCT) that addressed hot flashes (HF) in men with any stage of prostate cancer, treated with androgen deprivation therapy either medically or surgically. The studies addressed treatment for hot flashes where the main outcomes were frequency of hot flushes, distress from hot flushes, or hot flash score.
EXCLUSION CRITERIA Studies were limited to human studies and publications appearing between 1966 - 2009. Excluded were reviews & meta-analysis.
TOTAL REFERENCES RETRIEVED: 252
METHOD OF STUDY EVALUATION The Jadad score was used to assess the quality of the randomized controlled trial (RCT), on a five-point scale, and the QUORUM guidelines for systematic review were considered.
This summary did not include the measures that were used by the participants in reporting their hot flashes: i.e, diaries, skin temperature measurements, QOL surveys.
FINAL NUMBER STUDIED INCLUDED; N = 5 TOTAL SAMPLE SIZE: N = : 328 men were analyzed. SAMPLE RANGE ACROSS STUDIES : Sample sizes ranged from 12 - 177.
KEY SAMPLE CHARACTERISTICS: Samples included men with prostate cancer who had undergone surgical or medical castration and were currently experiencing hot flushes.
Phase of Care and Clinical Applications:
PHASE OF CARE Active Treatment
APPLICATIONS Late Effects and Survivorship; Elderly Care
In the five studies analyzed, the treatments that were studied included cyproterone acetate (CA), megestrol acetate (MA), gabapentin, transdermal clonidine, and diethylstilbestrol (DES). Unfortunately, none of the studies analyzed the same treatment. Because the studies looked at different interventions to relieve hot flushes (HF) in castrated men with prostate cancer, it was not possible to combine the studies to strengthen the outcomes. The studies' outcomes demonstrated varying degrees of success in relieving the hot flushes: Cyproterone acetate 100 mg, once per day, yielded 75% fewer HF than placebo (p<0.001), and 100% of men on CA had a 50% or greater reduction of mean number of HF, compared to placebo group. Megestrol acetate 20 mg, twice per day, yielded an 80% reduction of the median number of HF compared to a 19% reduction in the placebo group (p<0.001), an 87% reduction of median HF score vs. a 16% reduction for placebo (p<0.001), and a 50% or greater reduction of median number of HF (p<0.001) reported by 79% of MA group and 12% of placebo group. Gabapentin (4 schedules) achieved a 45.5% reduction of the median number of HF with 900mg gabapentin per day vs. 21.5% with placebo (p=0.02). Transdermal clonidine demonstrated no difference between the treated group and placebo. Diethylstilbestrol (1 mg) yielded a 100% reduction in the median number of HF vs.13% with placebo. 100% of DES and 14% of placebo reported a 50% or greater reduction of the median number of HF.
The systematic review of studies on treatment approaches to managing hot flushes in men after castration for prostate cancer showed very few such studies. Only five RCT studies were identified, and none of them analyzed the same treatment approach. Several of the studies that were presented demonstrated successful treatment approaches, including DES as the most effective, followed closely by MA and CA. However, these medications are linked to side effects that are not well tolerated by all patients.
Only five RCT studies were identified, and none of them analyzed the same treatment approach.
Large randomized placebo controlled studies are needed to clarify the data and provide clearer direction to managing HF in men who have been castrated as a treatment for prostate cancer. The summary, although providing insight for possible medical management, addressed only briefly the drop-out rates due to side effects. Further investigations of the drop-out subgroup could explore correlations among the medications to reveal unacceptable side effects in managing the participants’ hot flash symptoms. Further investigations comparing medications used and providing more specific information about measurements of QOL and hot flash reporting by participants are warranted.
Research Evidence Summaries
Irani, J., Salomon, L., Oba, R., Bouchard, P., & Mottet, N. (2010). Efficacy of venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for the treatment of vasomotor hot flushes in men taking gonadotropin-releasing hormone analogues for prostate cancer: a double-blind, randomised trial. Lancet Oncology, 11(2), 147-154.doi:10.1016/S1470-2045(09)70338-9
Compare the efficacy of 3 drugs in preventing hot flashes in men receiving hormone treatment for prostate cancer
Intervention Characteristics/Basic Study Process:
Patients were randomly assigned to receive wither venlafaxine delayed release 75 mg/day, medroxyprogesterone 20 mg/day or cyproterone acetate 100 mg/day in addition to leuprorelin injections. Patients were followed up at 4, 8 and 12 weeks. Patients completed daily hot flush diaries and categorised hot flush severity
- N 309 AGE Not reported
- MALES (%) 100% FEMALES (%)
- KEY DISEASE CHARACTERISTICS All had prostate cancer treated with hormonal therapy for at least 6 months. All had experienced 14 or more hot flushes in the week before study entry
Double blind randomized controlled trial
- Daily hot flush diary
European Organization for Research and Treatment of Cancer Quality of life questionnaire ( EORTC-QLC 30)
Patients in the medroxyprogesterone group had higher hot flash scores at baseline. The reduction in daily hot flush scores at 4 weeks was significantly lower for all 3 groups (p<.0001). Improvements were significantly lower in the venlafaxine group than either of the other 2 groups ( p = .0006), and patients ratings of efficacy of treatment showed that significantly fewer patients in the venlafaxine group rated the treatment as good ( p<.0001) compared to the other 2 groups. Adverse events related to the study drugs were not significantly different between groups, though cyproterone led to a non significantly higher number of vascular adverse events. The most frequent adverse events were gastrointestinal, including pain, constipation, diarrhea and nausea. GI events were more frequent with venlafaxine.
Men with significant hot flushes during androgen suppression for prostate cancer appeared to respond better to cyproterone acetate and medroxyprogesterone acetate than to venlafaxine
- Baseline sample/group differences of import
- Risk of bias (no control group)
- Other limitations/*explanation No control or placebo group precluded observation of placebo effect. The sample was limited to patients who sought treatment for hot flashes. This was a short follow up period - longer term efficacy is not known. Effects of hormonal treatment for hot flashes on prostate cancer are not known.
It appears that hormonal treatment is more effective in than venlafaxine for management of hot flashes in patients who are receiving androgen suppression for prostate cancer. Results also showed that many men did not seek treatment for this problem, suggesting that nurses may need to directly assess these patients for problems with hot flash symptoms. Effects of steroidal anti androgens on prostate cancer are not clear, and patients receiving both androgen suppression and cyproterone or medroxyprogesterone could have increases in prostate specific antigen concentrations.