Medicines Q&As
Q&A 183.4
Does progesterone or progestogen supplementation prevent
postnatal depression?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 6th February 2014
Background
Many women feel emotional in the first few days after giving birth with 30-75% of mothers
experiencing mood lows and highs and tearfulness. Symptoms peak in the first few days after giving
birth and usually pass by the tenth day after birth. Post natal depression is a more severe condition
which occurs in about 10-15% of women within 4 to 6 weeks of childbirth. The signs and symptoms of
post natal depression are similar to those experienced during major depression at other times and
include; low mood, tiredness, insomnia, loss of appetite, apathy, anxiety and feelings of guilt and
inadequacy [1-3].
Without treatment, most women recover spontaneously over 3-6 months, although around 10% still
have evidence of depression a year after delivery. Post natal depression may have important adverse
effects on the baby’s development as early interactions between the mother and baby may be
impaired. Long term studies have demonstrated impairment in cognitive and emotional development,
social adjustment and behavioural problems, particularly in boys [3].
The National Institute for Health and Clinical Excellence (NICE) and Scottish Intercollegiate
Guidelines Network (SIGN) guidance, as well as a Clinical Knowledge Summary, currently
recommend that all women are screened for depression and other mental health disorders in the both
the antenatal and postnatal period and offered appropriate treatment [4-6]. Current treatment for
postnatal depression includes self help approaches and brief psychological treatments including
counselling, cognitive behavioural therapy (CBT) and interpersonal psychotherapy (IPT).
Antidepressant therapy is used if there is no response to these measures [4-6].
Answer
Progesterone is an endogenous steroid hormone, which is necessary for implantation of the ovum
and for maintenance of pregnancy [7, 8]. Progestogens are synthetic compounds derived from and
with similar actions to progesterone; examples include norethisterone and medroxyprogesterone [7].
Progesterone acts on regions of the brain that are involved in mood control [9]. It has been
hypothesized that rapidly falling progesterone levels after birth are linked with the development of
postnatal depression [9-11]. Several small, poor quality studies have demonstrated either a weak
association or no association between the overall change in plasma progesterone levels and the risk
of developing depressive disorders following childbirth [12-15].
In patients with a previous episode of postnatal depression, recurrence has been reduced with a
schedule involving daily progesterone 100mg intramuscular injections from the completion of labour
for the first seven days, followed by progesterone suppositories 400mg twice daily until the return of
normal menstruation, or for two months [16].
In an open label, uncontrolled study, 100 pregnant women who had experienced previous postnatal
depression received progesterone prophylaxis by both the intramuscular and rectal routes. Follow up
was performed at 6 months following delivery by either direct consultation or postal questionnaire. A
response was obtained from 94 women, of which 10% had developed postnatal depression [17]. This
was compared with a recurrence rate of 68% in a previous observational study [18].
In a second, open label study, 247 women with previous postnatal depression were encouraged to
receive both progesterone 100mg intramuscular injections for 7 days followed by 400mg
suppositories twice daily for 8 weeks postpartum or until menstruation after delivery. Follow up at 6
months was achieved in 215 women. Twenty one women, who did not receive progesterone, became
the control group and had a recurrence rate of postnatal depression of 67% opposed to 7% in the
treated group [19].
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
A small, double blind, cross over, placebo controlled trial comparing 200mg progesterone
suppositories twice daily with placebo suppositories in 10 women with postnatal depression, showed
no significant difference in the mean symptom scores [20].
A 36 year old lady with a history of severe postnatal depression following two previous normal
deliveries was treated with prophylactic progesterone after the birth of her third child. She received
daily intramuscular progesterone 25mg injections for one week and was then commenced on
progesterone suppositories 100mg twice daily for 2 months. The dose was then reduced to 100mg
daily for one month. No symptoms of postnatal depression or side effects were reported [21].
The effect of norethisterone on postnatal depression was assessed in double blind, randomised,
placebo controlled study involving 180 postnatal women using a non-hormonal method of
contraception. Participants in the study were randomly allocated to receive either a single dose of
norethisterone enanthate 200mg (1ml) or 1ml of normal saline placebo by intramuscular injection, 48
hours post delivery. Depressive symptoms were assessed using the Edinburgh Postnatal Depression
Scale (EPDS) and the Montgomery-Asberg Depression Rating Scale (MADRS). The highest score
obtainable on the EPDS is 30 and on the MADRS is 60. The primary outcome measures were
depression scores (as rated by EPDS and MADRS) at 6 weeks and 3 months postpartum [22].
Mean depression scores were significantly higher in the norethisterone 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 17β-oestradiol and progesterone concentrations were significantly
lower in the norethisterone group compared with the placebo group. The study authors concluded that
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 [22].
A Cochrane review published in 2008 concluded that synthetic progestogens do not have a
preventive effect and should be used with significant caution in postnatal depression [23]. The review
excluded the studies conducted by Dalton [19] and Van der Meer [20] as the methodological quality
was considered to be inadequate. The Cochrane review concluded that the effect of natural
progesterone on postnatal depression is unknown and more studies are necessary.
SIGN guidance published in 2012, regarding the management of perinatal mental health states that
there is some evidence that progestins may worsen outcome [5]. Current guidance produced by NICE
and a Clinical Knowledge Summary, regarding the management of depression in pregnancy, do not
include the use of progesterone or progestogens for the prevention of postnatal depression [4, 6].
Summary
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Many women feel emotional in the first few days after giving birth. Post natal depression is a more
severe condition which occurs in about 10-15% of women within 4 to 6 weeks of childbirth [1-3].
It has been suggested that rapid changes in plasma progesterone levels at childbirth may be
responsible for the development of postnatal depression [9-11].
Several small poor quality studies have demonstrated either a weak association or no association
between plasma progesterone levels and the development of depressive disorders following child
birth [12-15].
In a small number of studies progesterone supplementation, started immediately after the
completion of labour, prevented recurrence of postnatal depression [16-21].
The progestogen, norethisterone, may increase the risk of postnatal depression when given within
48 hours of delivery [22].
Progesterone supplementation is not included in current NICE guidance for the management of
postnatal depression [4, 6].
Current SIGN guidance specifically states that there is some evidence that progestins may
worsen outcome in postnatal women [5].
The effect of progesterone and progestins is currently unknown and more studies are necessary
[23].
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
Limitations
The use of progesterone for the treatment of other postpartum mental disorders such as mania or
postpartum psychosis is not considered.
References
1. Nonacs R, Cohen LS. Postpartum mood disorders: Diagnosis and Treatment guidelines.
Journal of Clinical Psychiatry 1998; 59 (suppl 2): 34-40.
2. Post Natal Depression: Information for patients. Royal College of Psychiatrists. London.
Last updated July 2012 accessed via
http://www.rcpsych.ac.uk/healthadvice/problemsdisorders/postnataldepression.aspx.
3. Anon. The management of postnatal depression. Drugs and Therapeutics Bulletin 2000;
38 (5): 33-37.
4. Antenatal and postnatal mental health: clinical guideline 45. National Institute for Health
and Clinical Excellence. April 2007. Accessed via
http://www.nice.org.uk/nicemedia/pdf/CG45fullguideline.pdf on 03/02/2014.
5. SIGN guidance 127. Management of Perinatal mood disorders. Scottish Intercollegiate
Guidelines Network. March 2012. Accessed via http://www.sign.ac.uk/pdf/sign127.pdf on
03/02/2014.
6. Depression-antenatal and postnatal. NICE Clinical Knowledge Summary. January 2013
Revised July 2013. Accessed via http://cks.nice.org.uk/depression-antenatal-andpostnatal#!topicsummary on 03/02/2014.
7. Progesterone monograph, last revised 30th January 2013. Martindale: The Complete Drug
Reference. London. Pharmaceutical Press. Electronic version. Accessed via
www.medicinescomplete.com on 03/02/2014.
8. Gurnell M et al Chapter 13.1 Principles of Hormone Action. In Warrell DA, Cox TM at al
(Eds) Oxford Textbook of Medicine. 5th edition 2010. Page 1791.
9. Kammerer M, Taylor A, Glover V. The HPA axis and perinatal depression: a hypothesis.
Archives of Womens Mental Health 2006; 9: 187-196.
10. Bloch M, Schmidt PJ et al. Effects of gonadal steroids in women with a history of
postpartum depression. American Journal of Psychiatry 2000; 157(6): 924-930.
11. Harris B. Biological and hormonal aspects of postpartum depressed mood. British Journal
of Psychiatry 1994; 164: 288-292.
12. Nott PN, Franklin M et al. Hormonal changes and mood in the puerperium. British Journal
of Psychiatry 1976: 128: 379-883.
13. Harris B, Lovett L et al. Maternity blues and major endocrine changes: Cardiff puerperal
mood and hormone study II. British Medical Journal 1994; 308: 949-953.
14. Harris B, Lovett L et al. Cardiff puerperal mood and hormone study III. Postnatal
depression at 5 to 6 weeks postpartum and its hormonal correlates across the peripartum
period. British Journal of Psychiatry 1996; 168: 739-744.
15. Klier CM, Muzik M et al. The role of estrogen and progesterone in depression after birth.
Journal of Psychiatric Research 2007; 41: 273-279.
16. Dalton K. Postnatal depression and prophylactic progesterone. The British Journal of
Family Planning 1994; 19 (suppl): 10-12.
17. Dalton K. Progesterone prophylaxis used successfully in postnatal depression.
Practitioner 1985; 229: 507-508.
18. Dalton K. Depression after childbirth (letter). British Medical Journal 1982; 284: 1332.
19. Dalton K. Successful prophylactic progesterone for idiopathic postnatal depression.
International Journal of Prenatal and Perinatal Studies 1989; 1: 323-327.
20. Van Der Meer YG, Loendersloot EW et al. Effect of high dose progesterone in post partum
depression. Journal of Psychosomatic Obstetrics and Gynaecology 1984; 3: 67-68.
21. Fitzgerald KH, Betke T. Progesterone to prevent postnatal depression. The Australian
Journal of Hospital Pharmacy 2000; 30:21-22.
22. Lawrie TA, Hofmeyr GJ, DeJager M et al. A double blind randomised placebo controlled
trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum
hormones. British Journal of Obstetrics and Gynaecology 1998; 105:1082-1090.
23. Dennis CL, Ross LE, Herxheimer A. Oestrogens and progestins for preventing and treating
postpartum depression (Review). Cochrane Database of Systematic Reviews 2008, Issue
4. Art No: CD001690. DOI:10.1002/14651858.cd001690.pub2. Last updated 30 Jul 2004.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
Available at http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001690.pub2/abstract
accessed 03/02/2014.
Quality Assurance
Prepared by
Vicky Gibson, East Anglia Medicines Information Service, The Ipswich Hospital NHS Trust.
Date Prepared
6th February 2014
Checked by
Katie Smith, East Anglia Medicines Information Service, The Ipswich Hospital NHS Trust.
Date of check
11th February 2014
Search strategy
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EMBASE; Search terms; depression, postpartum + progestins, Depression, postpartum, +
hormones, depression + progestins. Update 2014. depression.ti,ab + prog*.ti,ab; postnatal
depression".ti,ab;+ prog*.ti,ab. Limited to publications since 2011.
MEDLINE; search terms: depression + progesterone, depression, puerperal + progesterone, sex
hormone + depression; sex hormone + depression-puerperal; hormone + depression; hormone +
depression-puerperal. Update 2014 depression.ti,ab + prog*.ti,ab; postnatal depression".ti,ab;+
prog*.ti,ab, limited to publications since 2011
IDIS, search terms: depression postnatal + progesterone; plus search repeated using IDIS search
terms; disorder, depressives + progesterone/dydrogesterone/gestonorone. Update 2014;
depression + progesterone
Cochrane Library Search term: progesterone, postnatal, progestins.
Drugdex. Thomson Micromedex Healthcare Series. Accessed via http://www.thomsonhc.com
Search term progesterone..
NICE evidence: www.evidence.nhs.uk. Search terms postnatal depression
National Institute for Health and Clinical Excellence (NICE) Accessed via at
http://www.nice.org.uk/. search terms: postnatal depression
Scottish Intercollegiate Guidelines Network (SIGN). Accessed via www.sign.ac.uk. Search term:
postnatal depression.
Royal College of Psychiatrists. Accessed via www.rcpsych.ac.uk. Search term postnatal
depression.
British National Formulary No 66 .British Medical Association and the Royal Pharmaceutical
Society of Great Britain; Sept 2013. Accessed via www.bnf.org.uk on 03/02/2014. Search term
progesterone.
Martindale: The Complete Drug Reference, 2014. Accessed via www.medicinecomplete.com
Search term progesterone.
AHFS Drug Information Bethesda, MD: American Society of Health-System Pharmacists.
Electronic version, 2011. Accessed via www.medicinecomplete.com Search term progestogens.
Taylor D, Paton C, Kapur S. The South London and Maudsley NHS Foundation Trust and Oxleas
NHS Foundation Trust: Prescribing Guidelines. Informa Healthcare 11th edition (2012). Search
term: postnatal depression,
Bazire S. Psychotropic Drug Directory. HealthComm UK Limited. 2014. Search term: postnatal
depression, progesterone.
Oxford Textbook of Medicine 5th edition 2010.
Available through NICE Evidence Search at www.evidence.nhs.uk
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