Edlund 2002.

Methods	The study was designed as a randomised, double‐blind, cross‐over study. Treatment was preceded by a run‐in phase of one menstrual cycle in which blood loss was analysed day‐by‐day in order to find the part of the period where the most intense bleeding occurred. The women were then allocated with blinded randomisation.
Participants	20 women were included. 4 women were excluded from the per protocol analysis due to events during the study (bile stone, kidney stone, goitre and menopause); finally, 16 women remained for the per protocol analysis. Inclusion criteria: non‐pregnant women, 18 years of age or older, with regular menstrual cycles and menorrhagia (defined as MBL > 80 mL per cycle), prolonged bleeding time (> 570 seconds) not due to known or measured deficiency of coagulation factor II, factor VII, FVIII, factor IX, factor X or of the vWF, and with a normal‐sized uterus, were admitted to the study after receiving information and giving informed consent. Exclusion criteria: women with signs of lung, heart or endocrine diseases were excluded. Lactation, hormone therapy or curettage within 2 months prior to the start of the study, drug or alcohol abuse or other conditions possibly jeopardizing the welfare of the individual were also exclusion criteria. As were abnormal findings at gynaecological examination, including uterine myomas of clinical significance where surgery could be indicated.
Interventions	For one group (n = 8), the first treatment cycle contained desmopressin and the second placebo. For the other group, (n = 8) the first treatment cycle contained placebo and the second contained desmopressin (total 16 each for both placebo and desmopressin). Desmopressin nasal spray (Octostim®) at a concentration of 300 µg per inhalation was administered twice‐daily on the 2 days of maximal blood loss. Saline nasal spray was administered the same way to the placebo group. In the third (non‐randomised) cycle, all 32 women received active treatment with desmopressin combined with tranexamic acid, 1.5 g 3‐times daily, during the 2 treatment days.
Outcomes	1. Measurement of MBL (primary outcome for the study and for this review). Method: the women were instructed to collect all sanitary towels and tampons during the study period. Menstrual blood was extracted from sanitary material with 5% sodium hydroxide, and haemoglobin was thus transformed to alkaline hematin, which was measured spectrophotometrically at 540 nm. Blood loss could thereafter be calculated from individual blood haemoglobin concentration. 2. Adverse events (the second primary outcome of the study) was also reported. A total of 44 adverse events were reported during the study: 10 during placebo treatment, 8 during desmopressin treatment and 26 during combined treatment. Of the 26 adverse events during combined treatment, several concerned well‐known reactions to tranexamic acid, mainly nausea. The other outcomes reported (but not of interest to the review) were: 1. laboratory tests (B‐hemoglobin, B‐hematocrit, S‐ferritin, B‐platelet count, S‐bilirubin, S‐alanine aminotransferase, S‐aspartate aminotransferase, Palkaline phosphatase, S‐creatinine and differential counts). 2. coagulation assays included INR coagulation factor II, factor VII, factor X. and capillary bleeding time.
Notes	During whole of the study period concomitant use of drugs known to have an effect on MBL was not permitted.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Blinded randomisation " stated but how sequence was generated is not specified.
Allocation concealment (selection bias)	Unclear risk	"Blinded randomisation" stated but how allocation was concealed is not specified.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study was stated to be double blind (though who was blinded and how the blinding was done remains unstated)and both the medication and the placebo were used as nasal sprays in the same way.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The outcomes were objective.
Incomplete outcome data (attrition bias) All outcomes	Low risk	20 women were included. 4 women were excluded from the per‐protocol analysis due to events during the study (bile stone, kidney stone, goitre and menopause); finally, 16 women remained for the per protocol analysis.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Unclear risk	No mention of pharmaceutical funding or other potential sources of bias.