Medicines Q&As
Q&A 183.3
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: 12th December 2011
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), Scottish Intercollegiate Guidelines
Network (SIGN) and Prodigy guidance 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. 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].
Current NICE, SIGN and Prodigy guidance, regarding the management of depression in
pregnancy, do not include the use of progesterone or progestogens for the prevention of postnatal
depression [4-6].
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].
From the NHS Evidence website www.evidence.nhs.uk
1
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].
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.
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, SIGN or Prodigy Guidance for
the management of postnatal depression [4-6].
Limitations
The use of progesterone for the treatment of other postpartum mental disorders such as mania is
not considered.
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From the NHS Evidence website www.evidence.nhs.uk
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.
Updated May 2011 accessed via
http://www.rcpsych.ac.uk/mentalhealthinfo/problems/postnatalmentalhealth/postnataldepre
ssion.aspx on 12/12/2011.
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 12/12/2011.
5. SIGN guidance. Postnatal Depression and Puerperal Psychosis. Scottish Intercollegiate
Guidelines Network. June 2002. Reviewed 2005. Accessed via
http://www.sign.ac.uk/pdf/sign60.pdf on 12/12/2011.
6. Depression_antenatal and postnatal. Prodigy Guidance. October 2007 Revised March
2008. Accessed via http://prodigy.clarity.co.uk/depression_antenatal_and_postnatal on
12/12/2011.
7. Progesterone monograph, last revised 20th August 2011. Martindale: The Complete Drug
Reference. London. Pharmaceutical Press. Electronic version. Accessed via
www.medicinescomplete.com on 12/12/2011.
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, Danaceau M 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, Van Loenen AC. 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
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From the NHS Evidence website www.evidence.nhs.uk
Quality Assurance
Prepared by
Vicky Gibson, East Anglia Medicines Information Service, The Ipswich Hospital NHS Trust.
Date Prepared
22nd December 2011
Checked by
Katie Smith, East Anglia Medicines Information Service, The Ipswich Hospital NHS Trust.
Date of check
30th January 2012
Search strategy
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Medline, search terms: depression, postpartum + progestins, Depression, postpartum, +
hormones, depression + progestins.
Embase, search terms: depression + progesterone, depression, puerperal + progesterone, sex
hormone + depression; sex hormone + depression-puerperal; hormone + depression;
hormone + depression-puerperal
IDIS, search terms: depression postnatal + progesterone; plus search repeated using IDIS
search terms; disorder, depressives + progesterone/dydrogesterone/gestonorone.
Pharmline, search terms: depression-postnatal + progesterone, depression + progesterone,
depression + hormone
Cochrane Library Search term: progesterone. Accessed via www.nlh.nhs.uk
Drugdex. Thomson Micromedex Healthcare Series. Accessed via http://www.thomsonhc.com
Search term progesterone.
National electronic Library for Medicine (NeLM) at www.nelm.nhs.uk. Search term:
progesterone, 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. Accessed
Search term: postnatal depression.
Clinical Knowledge Summaries Accessed via at http://cks.library.nhs.uk/. Search term:
postnatal depression
Royal College of Psychiatrists Accessed via www.rcpsych.ac.uk. Search term postnatal
depression.
British National Formulary No. 62.British Medical Association and the Royal Pharmaceutical
Society of Great Britain; Sept 2011. Accessed via www.bnf.org.uk on 12/12/2011. Search term
progesterone.
Martindale: The Complete Drug Reference, 2011. 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 10th edition (2009).
Search term: postnatal depression, progesterone
Bazire S. Psychotropic Drug Directory. HealthComm UK Limited. 2010. Search term: postnatal
depression, progesterone.
Oxford Textbook of Medicine 5th edition 2010.
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From the NHS Evidence website www.evidence.nhs.uk