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

Abstract

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-hberg Depression Rating Scale (MADRS) and the Edinburgh Postnatal Depression Scale (EPDS); 2. serum 17P-oestradiol, progesterone, testosterone and the 17P-oestradio1: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 17P-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 17P-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.

A systematic review, evidence synthesis and meta-analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost-effectiveness, safety and acceptability of interventions to prevent postnatal depression

“…l 37 trials reporting a universal preventive intervention 61,123,129,146,147,150,[153][154][155][156][157][180][181][182][183][184][185][186][187][197][198][199][200][207][208][209][210][211][212][217][218][219][220][225][226][227][228] l 20 trials reporting a selective preventive intervention 149,[158][159][160][161][162][163][188][189][190][191][192][201]…”

Influences of hormone-based contraception on depressive symptoms in premenopausal women with major depression

“…The depression scores of women who remained on Depo-Provera showed minimal change over one year. A randomized placebo-controlled trial of the progestin-only contraceptive norethisterone enanthate in 180 postpartum women found significant increases in the Montgomery Asberg and Edinburgh Postnatal Depression Scales (Lawrie et al, 1998). Thus, there is some literature suggesting that progestin-only forms of contraceptive may worsen mood in women who are susceptible to depression.…”

Progestogen-only contraceptive use among breastfeeding women: a systematic review

“…Another investigating the use of norethindrone compared with placebo found no difference between groups in breastfeeding initiation [33]. A third found no difference in breastfeeding outcomes over 12 weeks between women who received injectable norethisterone enanthate (NET-EN) or placebo [35].…”

“…Four RCTs [21,[33][34][35] investigated POC initiation within 6 weeks postpartum. A new RCT provides indirect evidence: this trial randomized 127 women planning to breastfeed to either POPs or combined oral contraceptives (COCs), started 2 weeks postpartum [21].…”