Oestrogen therapy and the menopausal syndrome

Clin Obstet Gynaecol. 1977 Apr;4(1):31-47.


Sixty-four patients with severe menopausal symptoms completed a four month double-blind placebo trial with conjugated equine oestrogens (premarin). Using a graphic rating scale system of assessment, a statistically significant improvement with premarin was observed in 12 psychological and symptomatic scores (Table 3). From a comparison between these results and the results of the 20 patients without vasomotor symptoms it would appear that many of these symptomatic improvements result from the relief of hot flushes (i.e. a domino effect). However, the improvement in memory and reduction of anxiety in these 20 patients suggest that oestrogens have a direct tonic effect on the mental state which is independent of vasomotor symptoms. Sixty-one patients with less severe menopausal symptoms completed the second twelve month double-blind placebo trial and, as assessed by graphic rating scales, a significant improvement with premarin was observed in five psychological and symptomatic scores (Table 3). In both the twelve and four month studies the marked placebo effect of "youthful skin appearance", and on skin greasiness in the twelve month study, indicate that no reliance can be placed on patient judgement of skin texture and appearance. Despite the lessening of the domino effect there was a slight improvement with premarin over placebo in 15 of the remaining 16 symptoms and it is likely that the cumulative effect of these small improvements results in an overall enhancement of well-being. The relief of atrophic vaginitis by premarin did not result in an improvement in libido and this suggests that the ability and the desire to have sexual intercourse are not related. The strength and duration of the placebo effect were well demonstrated in the three standard psychiatric scoring systems, the Beck score (for depression), the General Health Questionnaire and the Eysenck Personality Index (formula: see text) (for neuroticism). We observed a highly significant placebo effect extending for six months in all three, the improvement with premarin over placebo being non-significant. We must conclude that these tests are not sufficiently sensitive to assess psychological or symptomatic changes in menopausal women and that these changes are best assessed by the graphic rating scales. The number of side-effects and complications was assessed in the 61 patients in the long study. A higher incidence of minor side-effects was observed during premarin therapy; this was most marked in relation to leg cramps but radio-isotope scanning revealed no evidence of leg vein thrombosis in these patients or indeed in any patient in the study. Premarin caused no elevation of systolic or diastolic blood pressure; indeed there was a progressive fall in blood pressure throughout the study with no significant difference between premarin and placebo...

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Blood Pressure
  • Body Weight
  • Clinical Trials as Topic
  • Depression / therapy
  • Drug Evaluation
  • Emotions
  • Endometrium / cytology
  • Estrogens / adverse effects
  • Estrogens / pharmacology
  • Estrogens / therapeutic use*
  • Estrogens / urine
  • Female
  • Health
  • Humans
  • Hyperplasia / pathology
  • Menopause*
  • Personality Tests
  • Placebos
  • Time Factors
  • Uterine Diseases / pathology
  • Uterine Hemorrhage / etiology
  • Vagina / cytology
  • Vasomotor System / drug effects


  • Estrogens
  • Placebos