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
