A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones

Br J Obstet Gynaecol. 1998 Oct;105(10):1082-90. doi: 10.1111/j.1471-0528.1998.tb09940.x.


Objectives: To determine the effect of postnatal administration of the long-acting progestogen contraceptive, norethisterone enanthate, on postnatal depression and on serum hormone concentrations, and their association with depression.

Design: Double-blind randomised placebo-controlled trial.

Setting: A tertiary care hospital in Johannesburg, South Africa. POPULATION Postnatal women using a non-hormonal method of contraception (n = 180).

Methods: Random allocation within 48 hours of delivery to norethisterone enanthate by injection, or placebo.

Main outcome measures: Depression scores in the three months postpartum as rated by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17beta-oestradiol, progesterone, testosterone and the 17beta-oestradiol:progesterone ratio at six weeks postpartum.

Results: There was a chance excess of caesarean section deliveries in the progestogen group. Mean depression scores were significantly higher in the progestogen group than in the placebo group at six weeks postpartum (mean MADRS score 8.3 vs 4.9; P = 0.0111; mean EPDS score 10.6 vs 7.5; P = 0.0022). Mean serum 17beta-oestradiol and progesterone concentrations were significantly lower in the progestogen group compared with the placebo group at six weeks postpartum. There were no correlations between any of the hormone parameters and depression at six weeks except in the formula feeding subgroup of the placebo group, where formula feeding and 17beta-oestradiol concentrations were positively associated with depression.

Conclusions: Long-acting norethisterone enanthate given within 48 hours of delivery is associated with an increased risk of developing postnatal depression and causes suppression of endogenous ovarian hormone secretion.

Publication types

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

MeSH terms

  • Adult
  • Contraceptives, Oral, Synthetic / adverse effects*
  • Depression, Postpartum / blood
  • Depression, Postpartum / chemically induced*
  • Double-Blind Method
  • Estradiol / blood
  • Female
  • Humans
  • Norethindrone / adverse effects
  • Norethindrone / analogs & derivatives*
  • Postnatal Care / methods
  • Pregnancy
  • Progesterone / blood
  • Prognosis
  • Risk Factors
  • Testosterone / blood
  • Uterine Hemorrhage / etiology


  • Contraceptives, Oral, Synthetic
  • Testosterone
  • Progesterone
  • Estradiol
  • norethindrone enanthate
  • Norethindrone