Surrey 2002.

Study characteristics
Methods	Trial design: post‐treatment follow‐up analysis of a randomised, double‐masked, placebo‐controlled trial
Participants	Participants: 201 women were randomised; 99 women were analysed. Mean age:  Group A: 29.0 ± 1.0 years Group B: 29.0 ± 1.1 years Group C: 29.4 ± 1.0 years Group D: 28.9 ± 1.2 years Inclusion criteria: Regular menstrual cycle Symptomatic endometriosis, which had been diagnosed surgically within 12 months of entry with persistent or recurrent pain Symptomatic improvement over baseline at the end of the treatment period Did not terminate the treatment protocol because of worsening symptoms  Exclusion criteria:  Become pregnant Have surgical or medical intervention for endometriosis Have non‐endometriosis surgery that could have had an impact on pelvic pain during the treatment period Setting: United States of America (26 study sites) Timing: not stated
Interventions	Patients in all groups were to receive a depot preparation of the GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 52 weeks.  Group A: daily oral placebos for oestrogen and progestin add‐back (n = 51) Group B: daily oral norethindrone acetate (Aygestin, Lederle, Wayne, NJ) 5 mg and placebo for oestrogen (n = 55) Group C: received oral norethindrone acetate 5 mg and conjugated equine oestrogens (Premarin, Wyeth‐Ayerst, Philadelphia, PA) 0.625 mg daily (n = 47) Group D: received oral norethindrone acetate 5 mg and conjugated equine oestrogens 1.25 mg daily (n = 48)
Outcomes	Relief of overall pain Mean changes in lumbar spine bone mineral density Circulating cholesterol subfractions, triglycerides, and total cholesterol levels
Notes	Intention‐to‐treat analysis: yes Sample size calculation: yes  Funding: This work was supported by a grant from TAP Pharmaceutical Products, Inc., Lake Forest, Illinois. Financial Disclosure: Drs. Surrey and Hornstein have received grant support and honoraria as members of the speaker’s bureau of TAP Pharmaceuticals. Dr. Surrey is also a member of the Medical Advisory Board of TAP Pharmaceuticals. Ms. Fredrick performed the statistical analysis and is an employee of Abbott Laboratories, a parent company of TAP Pharmaceuticals.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were assigned randomly to one of four treatment groups by permuted blocks of four at each of the treatment sites".
Allocation concealment (selection bias)	Unclear risk	No details were presented on the method of concealment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐masked, placebo‐controlled study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐masked, placebo‐controlled study
Incomplete outcome data (attrition bias) All outcomes	High risk	123/201 completed 280 days of therapy.  Because of dropouts, the actual group‐specific sample sizes in the follow‐up period were lower than the numbers originally enrolled based on the initial power analyses. Thus, a post hoc analysis was performed.
Selective reporting (reporting bias)	Low risk	The study protocol was not available but it was clear that the published reports included all expected outcomes, including those that were prespecified.
Other bias	Low risk	No other risk of bias detected