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At the heart of general practice since 1960

The treatment - premenstrual syndrome

Consultant gynaecologist Mr Nick Panay offers his treatment advice for GPs managing PMS

There are a number of principles which should be adhered to when managing women with PMS. Although not evidence based, there is little doubt that reduction of stress, for instance, is a great help in ameliorating symptoms. Also, dietary measures such as avoidance of carbohydrate binges and limitation of alcohol and caffeine intake are often of benefit. There are data from non-randomised trials that exercise improves PMS symptoms, but in cases of moderate to severe PMS, it is important that medical therapy is instituted sooner rather than later to avoid unnecessary suffering. Women with marked underlying psychopathology, as well as PMS, should be referred to a psychiatrist. Symptom diaries (e.g. the daily record of severity of problems) should be used to assess the effect of treatment.

An evidence based approach should be undertaken in managing patients with severe PMS, as suggested in recent reviews of the condition.1,2

Standard current treatment

Ideally, women with severe PMS should be managed by a multidisciplinary team, which might comprise of a hospital or community gynaecologist, psychiatrist or psychologist, dietitian and counsellor. While such services are rarely provided in an NHS setting, referral to gynaecologists and psychiatrists should be reserved for women who have been fully evaluated as having severe PMS and when simpler forms of therapy have been explored.

A suggested treatment algorithm from the RCOG green top guideline for PMS is shown in figure 1.3 Most efficacious treatments for PMS are unlicensed. However, in this situation, unlicensed treatments can be justified where a body of evidence for efficacy and safety exist. The two chief evidence-based medical treatments of moderate-to-severe PMS are categorised by ovulation suppression and SSRIs. In making the decision between ovulation suppression and SSRIs the clinician should take the following into account:

1) Are the symptoms predominantly psychological, physical or a combination of both?

If symptoms have a significant physical component, it is logical that SSRIs or cognitive behavioural therapy (CBT) may not be of benefit for these symptoms

2) Does the woman express a preference for a psychological or a hormonal approach? 

Often women have strong views as to what treatment they will or will not accept. Some do not wish to have the condition medicalised and avoid all but complementary therapies. Others wish to avoid psychoactive drugs and others do not want their ‘hormones messed with’. Their requirement for contraception will also need to be taken into account. In the absence of evidence from head-to-head trials of different treatment modalities, it is not unreasonable to prescribe according to patient choice.

Figure 1: Updated algorithm for the management of severe PMS (modified from RCOG Green Top Guideline 481)

Please change above algorithm according to the following modifications:

First line

Exercise, cognitive behavioural therapy, vitamin B64

Combined new generation pill e.g. Yasmin, Cilest, Yaz, Qlaira (cyclically or continuously)

Continuous or luteal phase (day 15-28) low dose SSRIs e.g. citalopram / escitalopram 10 mg

Second line

Estradiol patches (100mcg) + micronised oral progesterone 200mg (Utrogestan – natural progesterone, licensed by the MHRA for progestogenic opposition in HRT) D17-D28 or Mirena

Higher dose SSRIs continuously or luteal-phase e.g. citalopram / escitalopram 20 – 40 mg

Third line GnRH analogues + addback HRT [(continuous combined estrogen + progesterone e.g. 50-100mcg estradiol patches or 2-4 doses of estradiol gel with Utrogestan 100mg /day) or tibolone)]
Fourth line Hysterectomy and bilateral oophorectomy + HRT (including testosterone)

 

Practice points for medical treatments of PMS:

  • Newer contraceptive pill types may represent effective treatment for PMS and should be considered as one of the first-line pharmaceutical interventions.
  • In view of their proven efficacy and safety in adults, SSRIs/SNRIs should be considered one of the first-line pharmaceutical management options in severe PMS.
  • When treating women with severe PMS, CBT should be considered routinely.
  • Percutaneous estradiol, either as an implant or as a patch, combined with cyclical progestogen, has been shown to be effective for the management of physical and psychological symptoms of severe PMS.
  • When treating women with PMS, treatment with the lowest possible dose of progestogen is recommended to minimise adverse effects.
  • GnRH analogue therapy results in profound cycle suppression and elimination of premenstrual symptoms. Lack of efficacy suggests a questionable diagnosis rather than a limitation of therapy.
  • There are insufficient data to recommend the routine use of progestogens or natural progesterone.
  • When treating women with severe PMS, hysterectomy and bilateral salpingo-oophorectomy has been shown to be of benefit.

There are a number of good clinical practice principles which should be observed in assessing response to treatment:

  • Response to treatment should not be assessed earlier than a minimum of three cycles.
  1. Adverse events are more common with initiation of treatment e.g. nausea with SSRIs/SNRIs and bleeding problems/progestogenic side effects with hormonal regimens
  2. Most treatments for PMS are not fully efficacious in the first few weeks, particularly hormonal regimens, which require three cycles to achieve full cycle suppression
  • If there is little or no response after three months, another treatment option in the same tier of the algorithm, or the next tier, should be moved onto or the diagnosis re-evaluated.
  • There may be a need to adjust the dosage or move to the next tier of treatments over time as some patients appear to have recurrence of their symptoms, possibly due to breakthrough of the ovarian cycle.

Most interventions are treatments and not ‘cures’ – the benefits only last for as long as the intervention is continued. Indefinite treatment should therefore be the norm rather than the exception. Discontinuation of treatment should be considered when pregnancy is contemplated.

Treatment should be continued during the perimenopause, as this is a time associated with potentially worsening of symptoms, but can be tentatively withdrawn when the patient is thought to be postmenopausal.

There may be a need to restart treatment if ovarian activity persists.

What’s newly available

Very few new options have been developed in the last decade due to lack of investment from pharmaceutical companies into research in this area. Yaz, a low dose contraceptive version of Yasmin, is licensed in some countries for the management of severe PMS (premenstrual dysphoric disorder). There is early work on synthetic neurotransmitters to modify the effect of hormonal fluctuations on the central nervous system. There is now good evidence that luteal phase SSRIs are as effective as continuous usage when treating PMS.5 Why their mechanism of action in PMS differs from that in chronic depression is unclear.

What has fallen out of fashion and why

Danazol is no longer used due to androgenic side effects, and hormone implant use is rare due to lack of availability of licensed options.  Progestogens and progesterone are no longer regarded as effective treatments for PMS and may induce symptoms in some women. Evening primrose oil may have some benefit for breast tenderness (though not currently licensed for this but is ineffective for other PMS symptoms)

Non-drug options and their evidence base

Lifestyle changes, such as reducing stress, diet, exercise, limiting alcohol and smoking cessation can improve PMS symptoms, but they will be insufficient in managing moderate-to severe-PMS. There is evidence that certain complementary therapies may be of benefit in such cases – Agnus Castus, St John’s Wort, phytoestrogens, calcium and vitamin D.6,7  Acupuncture, magnotherapy and homeopathy remain unproven options.

When treating women with PMS, complementary medicines may be of benefit, but clinicians need to consider that data from clinical studies are limited and underpowered, and interactions with conventional medicines should also be considered. The GP retains legal responsibility for the patient’s wellbeing when they refer patients to complementary therapists.

It is difficult to assess the true value of most of these therapeutic interventions because they are freely available without prescription or physician recommendation, with little regulation of efficacy or safety. If a complementary therapy is recommended, it is essential that the clinician is familiar with the evidence base for efficacy and safety of the product.

Mr Nick Panay is a consultant gynaecologist and specialist in reproductive medicine at Imperial College Healthcare NHS Trust and Chelsea & Westminster Hospitals. He is also chairman of the National Association for Premenstrual Syndrome and director of the Menopause and PMS Centre.

References

  1. Panay N. Management of premenstrual syndrome. J Fam Plann Reprod Health Care, 2009;35(3):187-94
  2. O’Brien S, Rapkin A, Dennerstein L, Nevatte T. Diagnosis and management of premenstrual disorders. BMJ, 2011;342:d2994
  3. Royal College of Obstetricians and Gynaecologists. Green-top guideline No. 48: the management of premenstrual syndrome. London; RCOG: 2007
  4. Wyatt KM, Dimmock PW, Jones PW, Shaughn O’Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: a systematic review. BMJ, 1999;318(7195):1375-81
  5. Marjoribanks J, Brown J, O’Brien PM, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev, 2013;6:CD001396.
  6. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo-controlled study. BMJ, 2001;322:134–7
  7. Burke BE, Olson RD, Cusack BJ. Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine. Biomed Pharmacother, 2002;56(6):283–8

Further Information/Reading

National Association for Premenstrual Syndrome: Advice for sufferers and health professionals. Web address: www.pms.org.uk

Premenstrual Syndromes: PMS and PMDD by Shaughn O’Brien (Editor), Andrea J Rapkin (Editor), Peter J Schmidt (Editor) Informa 2007.

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