A randomised comparison over 8 months of 100 micrograms and 200 micrograms twice weekly doses of transdermal oestradiol in the treatment of severe premenstrual syndrome.

OBJECTIVE

To determine the efficacy of a 100 micrograms twice weekly dose of Estraderm TTS compared with a 200 micrograms dose in the treatment of severe PMS, and to determine the overall acceptability of the treatment. To determine the serum oestradiol levels produced by the two doses of Estraderm and to discover whether the lower dose suppresses ovulation.

DESIGN

Main: randomised, prospective, comparative study. Subsidiary: cross-sectional and prospective.

SETTING

Premenstrual syndrome clinic in teaching hospital.

SUBJECTS

Women with severe PMS confirmed by prospective daily symptom recording.

INTERVENTIONS

Estraderm TTS at a dose of either 100 or 200 micrograms twice weekly continuously with either dydrogesterone 10 mg or medroxyprogesterone acetate 5 mg, from day 17 to day 26 of each cycle.

MAIN OUTCOME MEASURES

Main: change in total, exponentially smoothed, average maximum score (total-ESAmax) of 10 common premenstrual syndrome symptoms derived from Trigg's trend analysis and patient satisfaction. Subsidiary: plasma oestradiol and day 21 progesterone levels.

RESULTS

Main: no difference in change in total-ESAmax between Estraderm 100 micrograms and 200 micrograms groups. Greater drop-out rate and greater incidence of side effects attributed to oestrogen in higher dosage group. Satisfaction rate of 45% to 57% at eight months. Subsidiary: 1. Mean (95% CI) oestradiol level of 300 pmol/l (255 to 345) with Estraderm 100 micrograms and 573 (494 to 693) with Estraderm 200 micrograms; 2. Estraderm 100 micrograms suppresses mid-luteal progesterone from a mean (95% CI) of 35.5 (28.4 to 42.7) to 3.4 (2.4 to 4.5).

CONCLUSIONS

Estraderm TTS 100 micrograms twice weekly is as effective as 200 micrograms twice weekly in reducing symptom levels in severe premenstrual syndrome but is better tolerated. Estraderm 100 micrograms suppresses ovulation and results in a mean plasma oestradiol level similar to that observed in a spontaneous cycle.