Magill 1995.

Methods	RCT. Parallel, 2 arms: progesterone, placebo. Randomisation performed by pharmacy. No power calculation prior to study reported. ITT (mis‐diagnosed and per protocol)
Participants	Nr = 141, Na = 93: Aged 18 to 45 years. Experienced PMS in last three cycles. Agreed not to use oral contraceptives and discontinue other medication for PMS. Had no recent history of menstrual irregularity, psychotic illness or suicidal tendency. Did not misuse drugs or alcohol. Had not recently used antidepressants, benzodiazepines, therapy interfering with normal ovarian function or vitamin B6 preparations. Not eligible if recorded symptoms in only one cycle. PE rigorously excluded by protocol.
Interventions	400 mg progesterone pessary or identical placebo twice daily from 14 days before expected menstruation and until menstruation for 4 treatment cycles.
Outcomes	Highest scoring PMS symptoms daily on diary cards on four ‐point scale (0 = not present,1 = mild, 2 = moderate, 3 = severe). Average symptom scores. Blood pressure weight and height (in each cycle at surgeries). Eligible patients showed statistically significant improvement in all symptom scores. ITT analysis showed smaller improvement which was not significant at the 5% level except in the first cycle. PE excluded by the protocol.
Notes	48/141 participants dropped because symptoms recorded in only one cycle (6 progesterone 4 placebo), symptom severity too low in luteal phase or too high in follicular phase (16 progesterone10 placebo), taking medications not permitted by the protocol (8 progesterone 4 placebo). 2 pre‐treatment cycles for prospective records. Diary cards designed for the study. Only each participant's highest scoring symptom used since most significant clinically. AE no clinically significant changes in blood pressure, weight , severity or duration of menstrual bleeding in either group. 41/80 in progesterone group reported a total of 121 AE, 26/61 of placebo group reported a total of 53 AE. Incidence of nausea, breast pain and rectal pain similar in each group. Menstrual disorder (mostly changes in cycle length),vaginal pruritus and headache were more common in the progesterone group but only menstrual disorder statistically significant. AE generally mild. Two from each group withdrew because of AE‐ irregular menstruation and ovarian cyst in progesterone group, respiratory infection and depression in the placebo group. 2 stopped using placebo because they disliked pessaries. 1 using progesterone became pregnant after a long interval of infertility.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	quote "The randomisation schedule was prepared by Hoechst UK Ltd and, from memory, patient numbers were allocated to active or placebo.  Investigators recruited patients in sequence and patients were provided with trial supplies matching their trial numbers."
Allocation concealment (selection bias)	Low risk	See above
Blinding (performance bias and detection bias) All outcomes	Low risk	quote "Cyclogest and matching placebos were manufactured by Cox and Co. and presented in identical packing."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No reasons were given for withdrawals although they were separated according to treatment group. Changes from baseline for highest scoring symptoms only reported for per protocol subgroup, but changes from baseline for average symptom scores reported for both. Raw data were not available.
Selective reporting (reporting bias)	Low risk	Study protocol not available but the report includes all the outcomes of interest in the review.
Other bias	Low risk	ITT analysis performed. Ineligible participants excluded from per protocol analysis. Large size. (141 participants / 93 eligible) Baseline characteristics of participants in treatment and placebo groups for both ITT and per protocol shown.