Vanselow 1996.

Methods	RCT. 3 way crossover: vaginal progesterone/ oral progesterone/ placebo. No washoutcycle. Randomisation and concealment by pharmacy, blocked to max 10. Power calculation 45‐50 women needed to detect 25% difference in outcome with 95% power.
Participants	Nr = 39, Na = 22. Aged 18 to 45 years. Met DSM‐III rev. criteria for LLPDD: severe mood and physical symptoms 7‐10 days before menses included irritability or aggressiveness, alleviated within 3 days of onset of menstruation. Had 1 symptom‐free week. Using adequate non hormonal contraception, menstruating regularly and had experienced symptoms for past 6 cycles. Difference score on MDQ between follicular and premenstrual assessments of at least 20 points (represents two SDs). Had no current psychiatric disorder, nor coexisting medical or gynaecological disorder. Did not use psychotropic drugs or other hormonal preparations. Did not have major cyclical complaint of depression with anergia. PE excluded by symptom‐free week. Excluded menstrual migraine and stress like family crisis or violence.
Interventions	Two 200 mg oral progesterone at night and 1 in the morning with vaginal placebo OR two 200 mg vaginal progesterone at night and 1 in the morning with oral placebo OR both placebo.
Outcomes	Primary measure was MDQ administered on day 26 of second cycle: Follow up after 1 month approx. Secondary STPI, BDI, serum progesterone and metabolites day 26
Notes	Stopped recruitment when half number needed according to power calculation because no trends were seen. Did not use daily ratings. No major AE. One woman complained of nausea while on placebo and withdrew. One woman developed increasing depression while taking vaginal progesterone. One woman with history of thyrotoxicosis relapsed while taking vaginal progesterone. One woman had itchy skin on placebo but not on progesterone. Physical tiredness was not significantly different between treatment arms. Drowsiness and dizziness more frequent on oral progesterone. Vaginal irritation more frequent on vaginal progesterone.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomisation was performed by Besins‐Iscovesco Laboritoires (Paris) for a total of numbered treatment boxes given out sequentially."
Allocation concealment (selection bias)	Low risk	By pharmacy
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Probably done since prepared by pharmacy.
Incomplete outcome data (attrition bias) All outcomes	High risk	High attrition (22/39). Distribution of losses between groups not described, nor their effect considered.
Selective reporting (reporting bias)	High risk	Only the second month's records reported and that for only one day each cycle. Results were reported for each treatment phase but not as the difference from baseline for total MDQ scores, graphically, nor in means (standard deviations) for MDQ total or subscales, or BDI or STPI subscales. Daily ratings not analysed. Raw data not available.
Other bias	High risk	No ITT analysis. Baseline characteristics described only for the participants as a whole.

AE = adverse effects 
 bd = twice daily 
 BDI = Beck Depression Inventory 
 D = drug 
 DSM IIIR Diagnostic and Statistical Manual of the American Psychiatric Association, third edition revised 
 ITT = intention‐to‐treat analysis 
 MDQ = Moos' Menstrual Distress Questionnaire 
 Na = number of participants analysed 
 Nr = number of participants randomised 
 PE = premenstrual exacerbation of an underlying condition. 
 PMS = premenstrual syndrome. 
 severe symptoms = severe enough to interfere with work or relationships. 
 STAI = Spielberger's State Anxiety Inventory 
 STPI = State Trait Personality Index (Spielberger)