Discussion
sweats, night sweats
HEAT, RECRUITMENT, PATHOPHYSIOLOGY
This four-month RCT of oral micronized progesterone versus placebo for hot flushes and/or night sweats (VMS) in almost 200 perimenopausal women found no significant 3rd-m improvement in the overall VMS Score or primary outcome. Data, however, could not VMS occur in both postmenopause and perimenopause. Although their pathophysiology remains to be fully understood, they appear to be triggered by acute downward swings in estrogen levels leading to increased central stress hormone releases and elevated central norepinephrine levels leading to a narrowed thermoneutral zone that causes heat dissipation symptomsThis RCT was testing progesterone as a potentially effective VMS therapy in women in the menopause transition and perimenopause and showed it was effective for night sweats. Should perimenopausal women being treated for VMS with progesterone become postmenopausal, they could discontinue progesterone without experiencing a rebound in VMSOther trials of VMS have enrolled a few or some perimenopausal womenFunding played a role in study limitations. Funding was obtained for recruitment-extension for 1-year, however this timeline was still insufficient to achieve study completion of the 228 participants that were needed for adequate power. This study and the two previous perimenopause-only VMS RCT data were all underpoweredThe strengths of this RCT are that it meticulously followed Good Clinical Practice guidelines, and enrolled the largest number in a perimenopausal VMS trial participants to date. When local recruitment was slow, investigators transformed the design to offer and successfully accomplish remote participation with ethical accountability for experimental drugs and also achieved excellent participant retention (93%) and medication adherence. This trial, although designed a decade before the consensus on core outcomes for evaluating VMSDespite major efforts to learn the number of completed participants needed, to expand recruitment nationally, and to extend our RCT for one-year, we still were not able to randomize sufficient women. The results of this trial are not generalizable to all Canadian women since, despite a national catchment area, the majority of women were employed, higher educated, and White. Caution in interpretation of women’s night sweat improvements is needed since progesterone is RCT-documented to improve sleepOral micronized progesterone therapy in perimenopausal women experiencing bothersome night sweats and/or hot flushes was inconclusive and did not show superiority over placebo in a three-month RCT. However, a minimum clinically important VMS progesterone benefit could not be excluded. Participants on progesterone perceived significantly greater decreases in overall night sweats and improved sleep quality versus those on placebo. Perimenopausal interference with daily activities also significantly decreased on daily progesterone therapy. Progesterone is biologically identical to the lower progesterone levels occurring in perimenopause