1. Adherence to treatment.

Study	How defined	Assessment	HT group	Placebo group	Note
Barakat 2006	Discontinuation of therapy for longer than a month (or use of HT in placebo group)	Not stated	41.1% compliant for whole follow‐up period (median 3 years)	50.1% compliant for whole follow‐up period (median 3 years)
ELITE 2014	> 80% of prescribed treatment taken	Pill counts	Median > 98% over median of 5 years	Median > 98% over median of 5 years
EPAT 2001	Percentage of study medication consumed	Pill counts	Level of adherence 95% in the 87% of participants evaluated	Level of adherence 92% in the 92% of participants evaluated
EPHT 2006	> 80% of prescribed treatment taken	Number of collected and returned drugs and clinic reports	< 40% compliant at 3 years (estimated from graph)	< 30% compliant at 3 years (estimated from graph)
ERA 2000	Percentage of study medication taken	Pill counts	Level of adherence at 3.2 years: Women on unopposed oestrogen, measured in 79% of participants only: 74% Women on combined HRT, measured in 82% of participants only: 84%	Level of adherence at 3.2 years: Measured in 80% of participants only: 86% 5 women initiated treatment outside study
ESPRIT 2002	"Regular tablet use"	Self‐report to family doctor. Self‐report to study nurse at 6 weeks and whenever in contact with trial staff	Number non‐adherent: 51% at 12 months 57% at 24 months	Number non‐adherent: 31% at 12 months 337% at 24 months	Triallists attribute higher non‐compliance in HRT group to prevalence of vaginal bleeding (reported by 56% in HRT group, 7% in controls)
EVTET 2000	Adherence not described
Ferenczy 2002	Adherence not described
Greenspan 2005	"Taking at least 80% of medication for at least 80% of entire study period"	Pill counts 6‐monthly	90% adherent at 3 years	94% adherent at 3 years
HERS 1998	Taking at least 80% of study medication	Pill counts	79% adherent at 1 year 70% adherent at 3 years 3% initiated treatment outside study About 50% continued to use open‐label HRT during unblinded follow up (4.2‐6.8 years)	91% adherent at 1 year 81% non‐adherent at 3 years Less than 10% used HRT during unblinded follow‐up (4.2‐6.8 years)	Proportion of women who reported taking study medication at 1 year: HRT group: 82% Placebo group: 91%
KEEPS 2012	Pill or patch counts, percentage used	Pill counts or weights	94%‐95% in all groups, among women who completed trial at 4 years
Mulnard 2000	Taking at least 80% of study medication	Plasma oestradiol level evaluation at each visit Pill counts at each visit	No information given in publication
Nachtigall 1979	Adherence not described
Notelovitz 2002	Adherence not described
Obel 1993	Adherence not described
PEPI 1995	Taking at least 80% of study medication	Study diary reviewed at clinic visits Pill counts	Number adherent at 36 months: Women without uterus: 80%‐89% at 36 months Women with uterus: 1. On unopposed CEE: 44% 2. On combined therapy: 80%	Number adherent at 36 months: Women without uterus: 67% Women with uterus: 76%
Tierney 2009	Taking at least 80% of study medication	Pill counts weekly	No information given in publication
WAVE 2002	Percentage of study medication taken	Pill counts	At 2.8 years: Adherence 67% in the 78% of women analysed	At 2.8 years: Adherence 70% in the 81% of women analysed
WEST 2001	Percentage of study medication taken	Self‐report to study nurse 3‐monthly Computer chip in medication bottle records opening date and time Pill counts	At 2.8 years: Mean adherence including drop‐outs: 70% Mean adherence excluding dropouts: 90% 35% discontinued medication by 2.8 years, of whom 1% initiated treatment outside study	At 2.8 years: Mean adherence including dropouts: 74% over 2.8 years Mean adherence excluding dropouts: 90% 24% discontinued medication 2% initiated treatment outside study
WHI 1998 (unopposed oestrogen arm)	Taking at least 80% of study medication. Temporary discontinuation (e.g. during surgery) permitted	Weighing of returned medication bottles	At 6.8 years, about 53.8% of women were non‐adherent In addition, 5.7% of women had initiated hormone use through their own physician	At 6.8 years, about 53.8% of women were non‐adherent In addition 9.1% of women had initiated hormone use through their own physician
WHI 1998 (combined arm)	Taking at least 80% of study medication. Temporary discontinuation (e.g. during surgery) permitted	Weighing of returned medication bottles	42% non‐adherent by 5.2 years Of these, 6.2% initiated HRT outside study	10.7% crossed to active treatment by 5.2 years	Analyses censoring events 6 months after non‐adherence increased effect sizes
WISDOM 2007	Supply of study medication	Time at risk minus temporary interruptions and time after withdrawal from treatment	73% of time	86% of time	Women had a 3 month run‐in period on placebo. Only women who took 80% of tablets were randomised
Yaffe 2006	Supply of study medication	Patch counts: 75% use over 2 years counted as compliance	84%	84% of time	Women had a 1 week run‐in period. Only compliant women were randomised.