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


Correspondence: Professor G. J. Hofmeyr, Department of Obstetrics and Gynaecology, University of the Witwatersrand, Medical School, 7 York Road, Parktown, 2193, South Africa.


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 1. Depression scores in the three months postpartum as rated by the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17β-oestradiol, progesterone, testosterone and the 17β-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 = 0.01 11; mean EPDS score 10.6 vs 7.5; P = 0.0022). Mean serum 17β-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 17β-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.