Summary of findings for the main comparison. Oestrogen in combination with progestogen (sequential or continuous) compared to placebo for controlling symptoms of premenstrual syndrome.
| Oestrogen in combination with progestogen (sequential or continuous) compared to placebo. for controlling symptoms of premenstrual syndrome | ||||||
| Population: women diagnosed with symptoms of premenstrual syndrome (PMS) Setting: community Intervention: continuous oestrogen (implant or patch) plus progestogen Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with control | Risk with oestrogen in combination with progestogen | |||||
| Symptom scores over 2 to 4 menstrual cycles1 |
The difference in the mean change from baseline in symptom scores suggested a small to moderate benefit in the oestrogen group (SMD 0.27 lower, 95% CI 0.47 lower to 0.07 lower) | ‐ | 158 women, effective sample size 267 women considering cross‐over trials (3 RCTs) | ⊕⊝⊝⊝ VERY LOW 2,3,4 | ||
| Withdrawal due to adverse events over 2 to 4 menstrual cycles1 |
77 per 1000 | 49 per 1000 (20 to 122) | RR 0.64 (0.26 to 1.58) | 196 women, effective sample size 284 women considering cross‐over trials (3 RCTs) | ⊕⊝⊝⊝ VERY LOW 2,4,5 | |
| Specific adverse events over 2 to 4 menstrual cycles1 |
Two RCTs (total 206 women) assessed one or more of nine specific adverse events and all findings were inconclusive. Events assessed were bleeding, breast tenderness, headache, nausea, weight gain, dysmenorrhoea, skin irritation, skin reaction and skin pigmentation. | ⊕⊝⊝⊝ VERY LOW 1,6 | ||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the mean risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect | ||||||
1 Includes cross‐over trial(s), with cross‐over at 3 or 4 months
2Downgraded one level for serious risk of bias: poor reporting of methods in one study and/or high attrition, includes one or more cross‐over studies with unclear risk of carry‐over effects
3Downgraded one level for serious inconsistency: I² = 63%
4Downgraded one level for questionable applicability: one of the studies administered progestogen in both arms
5 Downgraded one level for serious imprecision: very few events and/or wide confidence intervals compatible with benefit in one or both arms or with no clinically meaningful effect
6Downgraded two levels for very serious imprecision: very few events and/or very wide confidence intervals compatible with benefit in one or both arms or with no clinically meaningful effect