Bertelli, G., Venturini, M., Del Mastro, L., Bergaglio, M., Sismondi, P., Biglia, N., … Rosso, R. (2002). Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: A randomized study. Annals of Oncology, 13, 883–888.

The study was designed to compare injected medroxyprogesterone vs. oral megestrol to control hot flashes in women with breast cancer.

Participants were randomized to two groups. Group 1 received I.M. depot MPA (500 mg on days 1, 14, and 28) and Group 2 received oral megesterol acetate (40 mg po daily days 1-42).

Eligible patients were postmenopausal females with a history of breast cancer, without evidence of relapse, whom had been suffering from hot flashes for at least 1 month prior to study entry. Group 1 enrolled 3 , and Group 2 enrolled 34.  Major Inclusion/Exclusion Criteria:

• Concurrent adjuvant tamoxifen 20 mg/day was allowed if started at least 1 month before study entry and if the planned residual duration of treatment was at least 6 months.
• No concurrent treatment with estrogens, androgens, progestins, corticosteroids, clonidine, veralipride, or ciclophenile was allowed.
• Patients who had received adjuvant chemotherapy had to have concluded treatment for more than 2 months.

Not described

The primary endpoint was the proportion of responding patients after 6 weeks of treatment (7 weeks after randomization). A patient was classified as a responder if she achieved a greater than 50% reduction in frequency of hot flashes and hot flash score. Frequency and severity of hot flashes were monitored through self compiled diaries. The three main efficacy parameters were:

1. Changes in average number of hot flashes per day
2. Average daily ‘hot flash score’ compared to baseline
3. Proportion of participants who obtained greater than 50% reduction in frequency and reduction in HF score as compared to baseline score

The mean number of hot flashes and hot flash scores did not differ significantly at baseline between the two groups. Differences between the two groups at week six were not statistically significant. Good control by both treatments was apparent. No significant difference in the proportion of responders between the two arms was observed (p=0.567) Overal,l 50 of 71 patients (70.4%, 95% CI 58-81%) achieved a response as previously defined.Maintenance of response in the group of 50 initial responders was assessed at 2-monthly follow up visits for 6 months after randomization. By patient report, a difference in the duration of response was observed: out of 28 responding patients in the MPA group, 25 (89.3%) were still responding at 6 months. In the megestrol group, only 10 of the initial 22 responders (45.4%) were still in response after 6 months.

For an 80% power and two sided 5% significance, 90 subjects were planned. Only 71 were accrued. After randomization, five patients in each group refused to start the assignment and withdrew from the study. Two more patients, both in group one, were found ineligible (one for medical contraindication and one not postmenopausal) and withdrawn. Six patients did not provide complete diary recordings during treatment (five patients who dropped out before completion for side effects and one who was lost to follow-up). Treatment allocation was not double-blinded because this would have required administration of I.M. placebo in group 2 which was judged impractical.