17 beta-estradiol and norethisterone acetate in low doses as continuous combined hormone replacement therapy

Maturitas. 1996 Feb;23(1):31-9. doi: 10.1016/0378-5122(95)00949-3.


Objectives: To evaluate low doses of 17 beta-estradiol (E2) and norethisterone acetate (NETA) as continuous combined hormone replacement therapy (HRT) in their effects on vasomotor symptoms, bleeding episodes, endometrial histology and mastalgia.

Method: Sixty postmenopausal women were randomly allocated to three treatment groups and were given 1 mg E2 and 0.25 mg NETA (A), 1 mg E2 and 0.5 mg NETA (B) and 2 mg E2 and 1.0 mg NETA (C) in daily doses. The treatment period was 1 year.

Results: A similar statistically significant reduction of climacteric symptoms (P < 0.05) was found in all groups. Bleedings, mainly as spottings, occurred most commonly during the first treatment months. Fewer bleeding episodes and a higher percentage of amenorrhea was noted in group B compared to the other groups but did not reach statistical significance. All endometrial biopsies showed atrophy. Women in group A and B had less severe mastalgia (P < 0.05) compared to group C, given higher doses of steroids.

Conclusion: Postmenopausal women taking 1 mg of E2 plus 0.5 mg NETA as continuous combined HRT reported a marked reduction of climacteric complaints and good bleeding control. No endometrial proliferation was detected after 1 year of treatment. This type of therapy may be beneficial especially for elderly women, in whom bleeding may be annoying.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amenorrhea / drug therapy
  • Amenorrhea / physiopathology
  • Atrophy / complications
  • Atrophy / pathology
  • Atrophy / physiopathology
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Endometrium / pathology
  • Endometrium / physiopathology
  • Estradiol / standards
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy / standards*
  • Female
  • Humans
  • Middle Aged
  • Norethindrone / standards
  • Norethindrone / therapeutic use*
  • Progesterone Congeners / standards
  • Progesterone Congeners / therapeutic use*
  • Uterine Hemorrhage / drug therapy
  • Uterine Hemorrhage / etiology
  • Uterine Hemorrhage / physiopathology
  • Vasomotor System / physiology


  • Progesterone Congeners
  • Estradiol
  • Norethindrone