Volpe 1986.

Methods	Parallel‐group RCT
Participants	113 postmenopausal women with menopausal symptoms: 81 were naturally menopausal (mean age 51 years); 32 were post hysterectomy and oophorectomy (mean age 41 years) Last menstrual period 1 to 5 years previously Excluded women who had received hormone preparations during preceding 8 weeks or in whom oestrogen therapy was contraindicated Dropouts: 11/15 in placebo group dropped out by 6 months
Interventions	Tibolone 2.5 mg daily (n = 27) vs Placebo (n = 15) Oestrogen: oestriol (E) 2 to 4 mg/d (n = 21) HT (total n = 50) Conjugated oestrogens (CEE) 0.625 mg/d for 21 days + norethisterone (NET) 5 mg/d on days 12 to 21 (n = 15) CEE + cyproterone acetate (CPA) 12.5 mg/d from day 1 to day 10 (n = 15) Oestradiol valerate (EV) 2 mg/d for 21 days + sequential NET (n = 10) EV 2 mg/d for 21 days + CPA 12.5 mg/d from day 1 to day 10 (n = 10) All for 6 cycles
Outcomes	Hot flushes, scored as follows: 0 = absent, 3 = mild, 6 = moderate, 9 = severe No comparative data on AEs were reported. Endometrial hyperplasia was reported, but no histology was done in the placebo group
Notes	Menopausal symptoms measured on a non‐validated questionnaire Timing: unclear Trial location: Italy Multi‐centre: no; single site
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States “randomly allocated". Baseline characteristics of groups not mentioned
Allocation concealment (selection bias)	Unclear risk	Method not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	No information about blinding provided. Blindness unlikely at least for providers/researchers (it is a placebo‐controlled trial)
Blinding of outcome assessment (detection bias) All outcomes	High risk	Histology assessment blinded, but symptoms evaluated through a questionnaire; unlikely that providers/researchers were blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	High attrition in placebo group (11/15), numbers assessed for hot flushes in active groups not reported
Selective reporting (reporting bias)	Unclear risk	Study protocol not available
Conflict of interest	Unclear risk	No information provided about conflicts of interest. Non‐validated measure used for VM symptoms