Nachtigall 1979.

Methods	Stated purpose: to evaluate effects of HT Stratification: not mentioned Unblinding: code broken if a major medical complication or death occurred (13 times in HT group, 17 times in control group) No. of women screened for eligibility: 403 (235 excluded: 74 ineligible, 31 refused, 130 no match for pair found) No. randomised: 168 No. analysed: 168 Losses to follow‐up: none Adherence to treatment: not mentioned Analysis by intention to treat: yes, although any events occurring after unblinding were not recorded No. of centres: 1 Years of recruitment: unclear ‐ study lasted 10 years and was complete by 1976 Design: parallel Funding: not stated
Participants	Included Postmenopausal inpatients with chronic disease (last menstrual period > 2 years previously, FSH > 105.5 mU, total urinary oestrogen < 10 micrograms/dl), never taken HT. All hospitalised for entire study period; screened with history, physical examination, medical record review; matched on the basis of chronic disease diagnosis, as follows: diabetes mellitus (14 pairs), custodial care (20 pairs), arteriosclerosis (9 pairs). Other pairs matched on the basis of chronic neurological disorders Excluded Acute heart disease, hypertension (blood pressure > 160/94), apparent malignancy, hysterectomy Mean age: 55 Baseline equality of treatment groups: Correlation for diagnosis was identical. Correlation for some other risk factors was low between individual pairs, but group means were similar. Country: New York Hospital for Chronic Diseases
Interventions	HT arm: CEE 2.5 mg daily, plus MPA 10 mg for 7 days each month Control arm: placebo Duration: 10 years
Outcomes	Death, myocardial infarction, "serious embolism" (pulmonary embolus), breast cancer, colon cancer, endometrial cancer, gallstones
Notes	Power calculation: not mentioned Re generalisability: Study authors point out that almost all women had long‐term chronic disease, were hospitalised for the entire study period, had much lower than normal overall parity and had more prolonged bed rest than the average woman.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Women matched for diagnosis of chronic disease. From matched pairs, research nurse randomly selected which member would be assigned to which group. Method not described
Allocation concealment (selection bias)	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up described. Analysed by intention to treat, but any events occurring after unblinding not recorded
Blinding of participants and personnel (performance bias) All outcomes	Low risk	States participants and research physicians blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	States participants and research physicians blinded
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	Unclear risk	Correlation for some baseline prognostic factors was low between individual pairs, but group means were similar.