The effect of norethisterone enantate on postnatal depression

Abstract

Background Postnatal depression affects approximately 10% of women and is responsible for considerable postnatal morbidity. Progestogens have psychoactive and endocrine properties and progesterone deficiency has been considered as an aetiological factor in postnatal depression. Although progesterone is used in the prevention and treatment of postnatal depression, progestogens may cause depressive symptoms. The psychological impact of using progestogen contraceptive agents in the postnatal period is unknown.

Objectives To determine the effect of postnatal administration of the long-acting progestogen contraceptive, norethisterone enantate, on postnatal depression and on serum sex 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-hormon al method of contraception (n -1 8 0 ).

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

Main outcome measures 1) Depression scores in the first three months postpartum as rated by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS). 2) Serum 1 7|3-oestradiol, progesterone, testosterone and the 17|3-oestradiol:progesterone ratio at six weeks pospartum.

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 [0.9] vs 4.9 [1.1], p = 0,0111; mean EPDS score 10.6 [0.7] vs 7.5 [0.8], p = 0.0022). Mean serum 17f3-oestradiol and the 17P-oestradio!:progesterone ratio were significantly lower in the progestogen group compared to the placebo group, with the lowest levels occurring in breast-feeding women in the progestogen group. 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 17p-oestradioi concentrations were positively associated with depression.

Conclusions Norethisterone enantate given within 48 hours of delivery is associated with an increased risk of developing postnatal depression and causes suppression of endogenous 17(3-oestradiol secretion below levels induced by lactation. Progestogen contraceptives should be used with caution in the postnatal period, particularly in women with a history of depression.