Summary of findings 2. Progesterone compared to placebo for seizures in catamenial epilepsy.

Progesterone compared to placebo for seizures in catamenial epilepsy
Patient or population: women with seizures due to catamenial epilepsy Settings: outpatients Intervention: progesterone Comparison: placebo
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Progesterone
Seizure freedom: all seizures Follow‐up: 12 weeks	No women in the placebo group achieved freedom from all seizures.	4% of women in the progesterone group achieved freedom from all seizures.	RR 4.03 (0.21 to 76.21)	130 (1 study)	⊕⊕⊝⊝ low1,2	There was also no significant difference between treatments in terms of freedom from the most severe seizure type (RR 2.09, 95% CI 0.61 to 7.10).
Responder rate: 50% or greater reduction in all seizures Follow‐up: 12 weeks	200 per 1000	228 per 1000 (112 to 464 per 100)	RR 1.14 (0.56 to 2.32)	130 (1 study)	⊕⊕⊕⊝ moderate1	There was also no significant difference between treatments in terms of responder rate for the most severe seizure type (RR 1.24, 95% CI 0.67 to 2.29) or when considering each seizure type individually (complex focal, simple focal, secondary generalised seizures).
Change in seizure frequency Follow‐up: 12 weeks	1 study (n = 36) reported that the decrease in seizure frequency from baseline in the progesterone group was significantly higher than the decrease in seizure frequency from baseline in the placebo group (P = 0.024).   1 study (n = 130) reported no significant differences between treatments with respect to proportional changes for all seizures combined, most severe seizure type, or each seizure type considered separately (complex focal, simple focal, secondary generalised seizures).		NA	166 (2 studies)	⊕⊕⊝⊝ low1,3	Due to different methods of data presentation, results could not be combined in meta‐analysis.
Number of withdrawals from the study: for any reason Follow‐up: 12 weeks	141 per 1000	219 per 1000 (114 to 422 per 1000)	RR 1.56 (0.81 to 3.00)	168 (2 studies)	⊕⊕⊕⊝ moderate1	There was also no significant difference between progesterone and placebo in terms of treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17).
Adverse events: any adverse event Follow‐up: 12 weeks	511 per 1000	434 per 1000 (302 to 634 per 1000)	RR 0.85 (0.59 to 1.24)	130 (1 study)	⊕⊕⊕⊝ moderate1	There was no significant difference between progesterone and placebo in the proportion of women experiencing specific adverse events occurring in at least 5% of participants (diarrhoea, dyspepsia, nausea, vomiting, nasopharyngitis, fatigue, dizziness, headache, and depression).   In the other study (n = 36), 2 women were excluded from the study due to progesterone side effects (severe headache, nausea and vomiting). No further information on adverse events was provided in this study.
Quality of life Follow‐up: NA	Outcome not reported.				NA
*The basis for the assumed risk is the event rate in the placebo group. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; NA: not applicable; RR: risk ratio
GRADE Working Group grades of evidence   High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

¹Downgraded once due to risk of bias: unclear methodological information regarding allocation concealment and attrition in the included trial(s). One of the trials was terminated early due to futility analyses and is therefore statistically underpowered.
²Downgraded once due to imprecision: confidence intervals around the treatment effect are very wide due to the small number of events.
³Downgraded once due to inconsistency: results of the two studies could not be combined in meta‐analysis due to different methods of presenting the outcome. Study‐specific results are not consistent and lead to different conclusions.