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Diagnosis and management of premenstrual disorders
Clinical Review from the BMJ
Sources and selection criteria
Box 1 Criteria for diagnosing the core premenstrual disorder
How are premenstrual disorders managed?
The consultation and treatment planning
Box 3 outlines an approach to careful history taking. Bearing in mind available treatment options, it is important to review the patient’s previous treatment and her future plans for pregnancy or contraception. Ask the woman whether psychotropic therapy, endocrine agents, surgery, or an intrauterine system are acceptable. The severity of symptoms and the degree of impairment will usually dictate the level of invasiveness of any intervention used. The condition can be treated by psychotropic drugs or suppression of ovulation with a hormonal agent that does not reinstitute the symptoms, and it is important to communicate this clearly to the patient.
Box 2 Symptoms
Box 3 Minimum information to be obtained in first two clinic or surgery appointments
Which treatments can be effective without suppressing ovulation?
Non-drug based treatments
Box 4 summarises non-drug based approaches to management that are supported by some research evidence and expert consensus. These approaches may be more effective for womenwith less severe symptoms. Dietary recommendations and herbal supplements have not been studied robustly. The only herbal supplement that has been shown to be effective in small placebo controlled trials is fruit extract of Vitex agnus castus.13 Placebo controlled studies show that calcium, vitamin B-6, and exercise may be superior to placebo. A programme of 10 cognitive behavioural therapy sessions that included relaxation, stress management, and assertiveness training, has been reported to be effective and comparable to treatment with fluoxetine over six months, with cognitive behavioural therapy possibly having a longer duration of effect when assessed at 12 months.14
Spironolactone 100 mg/day given in the luteal phase has been shown in randomised placebo controlled studies to reduce abdominal bloating, swelling, breast discomfort, and mood symptoms.15
Meta-analyses of placebo controlled trials have found that selective serotonin reuptake inhibitors (SSRIs; fluoxetine, paroxetine, citalopram, sertraline) or serotonin and noradrenaline reuptake inhibitors (SNRIs; venlafaxine) are effective in reducing mood and physical symptoms when used continuously or 14 days before menses (usually at a lower dose than that recommended to treat a mood disorder).16-18 Symptoms may improve within 48 hours of beginning treatment. Irritability is particularly responsive. SSRIs are licensed in the US, but not in the United Kingdom, for the management of premenstrual dysphoric disorder.
Box 4 Treatments
The reversible side effects of SSRIs seem to be less common with intermittent treatment. These include fatigue, insomnia, nausea, gastrointestinal disturbance, headache, sweating, and tremor. Continuous use has been associated with decreased libido and difficulty achieving orgasm. Dizziness, lethargy, nausea, irritability, low mood, and vivid dreams are all symptoms of serotonin withdrawal and are rarely reported with intermittent treatment.18 SSRIs and oral contraceptives can be given concurrently without decreasing the efficacy of either class of drug. Obviously, some patients may become pregnant while taking SSRIs and these drugs have not been shown to be teratogenic.
Continuous treatment with SSRIs or SNRIs may be a more logical approach for patients with premenstrual exacerbation of an affective disorder.
No studies have directly compared the psychotropic agents so there is no evidence to suggest that one preparation works better than another. Moreover, the response to one SSRI does not predict the efficacy, side effects, or outcomes of another. Different drugs, doses, and timings should be tried empirically in individual patients.
Certain anxiolytics (alprazolam, buspirone) have been shown in placebo controlled studies to be superior to placebo18 20 21 but seem to be less effective than SSRIs. The side effect profiles of these agents and risks of dependence make them less desirable options than SSRIs.
How can we treat premenstrual disorders using hormones?
Hormonal treatment that does not suppress ovulation
Progesterone and progestogens (norethisterone, medroxyprogesterone acetate, levonorgestrel) administered in the luteal phase are the only hormonal agents licensed for managing premenstrual syndrome in the UK. However, a systematic review showed that they are ineffective and often restimulate the symptoms.4 These agents are useful only for endometrial protection during treatment with oestrogen to suppress ovulation. Treatment by suppression of ovulation Ovulation can be suppressed with oral contraceptives, gonadotrophin releasing hormone (GnRH) agonists, the gonadotrophin inhibitor danazol, oestrogen, and by removal of the ovaries (box 5).
Treatment by suppression of ovulation
Ovulation can be suppressed with oral contraceptives, gonadotrophin releasing hormone (GnRH) agonists, the gonadotrophin inhibitor danazol, oestrogen, and by removal of the ovaries (box 5).
Oral contraceptive agents suppress ovulation but introduce a new exogenous endocrine cycle that can lead to progestogen induced symptoms. A newer oral contraceptive that contains drospirenone and 20 μg of ethinylestradiol, consisting of 24 active followed by four placebo pills, may counteract this effect. This regimen is not currently available in the UK. Drospirenone has antidiuretic and antiandrogenic properties, and, in combination with the lower dose of ethinylestradiol administered in the above 24/4 regimen, suppresses ovulation and treats symptoms effectively without regenerating physical or psychological symptoms, according to two randomised controlled trials.22 23 The 20 μg pills do have higher rates of breakthrough bleeding, as noted in a recent Cochrane review. The benefits for premenstrual disorders may still apply using a 30 μg ethinylestradiol and drospirenone oral contraceptive pill in the standard 21/7 regimen.24
GnRH agonist analogues
Several randomised controlled trials have shown that GnRH agonists are effective in relieving symptoms of premenstrual disorders.25 Long acting GnRH suppresses ovarian steroid production, resulting in a “medical menopause” and hence relief of premenstrual syndrome. The induced hypo-oestrogenic state can cause hot flushes and night sweats, low mood, insomnia, and eventually osteoporosis. “Add back” treatment with combinations of oestrogen and progesterone or tibolone efficacy. There are few long term safety data for GnRH agonists with add back treatment. GnRH agonist analogues do not prevent pregnancy, so contraception must be used. Tibolone appears less likely to reintroduce premenstrual symptoms than cyclical oestrogen and progestogen according to a recent meta-analysis.25 It may be useful to consider a “trial” of GnRH agonists to establish the relative contributions of endocrine related pathology versus underlying psychopathology in patients with premenstrual exacerbation, or to mimic the effect of a bilateral oophorectomy to determine the potential benefit of surgery.
Danazol is androgenic, and a randomised placebo controlled crossover trial found considerable benefit over placebo in the treatment of patients with premenstrual syndrome.26 Administration during the luteal phase only is beneficial for cyclical mastalgia but no other symptoms of the syndrome. Its side effects are predominantly androgenic and include acne, hirsutism, weight gain, voice change and deepening, adverse lipid profile, and teratogenesis.
Transdermal patches and subcutaneous implants of estradiol are effective in suppressing ovulation.27 The use of unopposed oestrogen may lead to endometrial hyperplasia and increases the risk of endometrial cancer. Providing endometrial protection with progestogen is important, but if administered orally progesterone may induce premenstrual symptoms. Using a levonogestrel releasing uterine system theoretically avoids this problem because the progesterone effects of this system are intended to be local, although some women experience premenstrual symptoms and breast tenderness in the early months of treatment. The combination of oestrogen administration and the levonogestrel releasing intrauterine system will protect the endometrium, provide contraception, and reduce menstrual flow in women who also have heavy menstrual bleeding. Although not recent, randomised controlled trials have shown the efficacy of oestrogen in suppressing ovulation and managing symptoms.27 28 However, the suppression of ovulation is not sufficiently assured for contraceptive purposes and patients should be advised appropriately.
Is surgery a reasonable option?
Endometrial ablation or hysterectomy will eliminate menstruation but not premenstrual symptoms because ovarian function is conserved. Women with severe and debilitating symptoms may request bilateral oophorectomy. This may be considered, but we recommend careful counselling of the woman to outline the drawbacks and consequences of a premature surgical menopause. It is important to replace oestrogen until the age of the natural menopause. Removing the uterus when oophorectomy is performed allows women to receive unopposed oestrogen replacement and avoid recurrent progestogen induced premenstrual symptoms. A trial of GnRH is advisable before deciding to perform bilateral oophorectomy and hysterectomy. Women with severe premenstrual syndrome who are undergoing hysterectomy for another gynaecological indication may also elect to have their ovaries removed to avoid ongoing premenstrual symptoms.
Box 5 Suppression of ovulation
A patient’s perspective
I have always had severe mood swings, but over the past few years they got worse. They lasted for days and left me physically and emotionally exhausted. I was verbally aggressive and so nasty that when the mood had passed I would be devastated by my actions. This had a huge effect on my relationship with my son; I couldn’t book holidays or outings because I would spoil them. I became a hermit for a couple of years. I tried many prescription drugs including citalopram, over the counter remedies, and I trawled the internet but nothing came close to working. At this point I was desperate. My general practitioner referred me to a consultant gynaecologist who gave me mood diaries to fill in. These showed that my symptoms occurred before menstruation and got better during my period—I had typical premenstrual syndrome. I received injections of a gonadotrophin releasing hormone agonist (Prostap) and later a levonorgestrel releasing intrauterine system and oestrogen patches. Initially, my moods were very up and down, then one day I suddenly realised that I hadn’t had a symptom for a while. Now I can’t remember when I had my last one. Recently, I was talking to my son who gave me the biggest hug going and said “I’ve got my mum back.”
Managing premenstrual disorders in general practice
The figure shows how different premenstrual disorders may be presented on the daily record of severity of problems chart. The diagnosis of a premenstrual disorder should be based on two months of recording using a paper or electronic based system of rating symptoms, and this is easily done in primary care. It is of course difficult to send away a severely affected patient without treatment but this initial process is essential. No woman should wait to be seen in secondary care only to be sent away for two months of chart recording because this can easily take place between referral and consultation. The prospective record of symptoms will give the clinician an idea of whether there is a positive diagnosis and how severely the woman is affected. Women who have premenstrual symptoms that are debilitating but who are symptom free for at least one week after menstruation have core premenstrual disorder. Their symptoms may or may not fit the diagnostic criteria for premenstrual dysphoric disorder. Treat these women as outlined above according to their wishes after all information is presented. A hierarchical approach that takes into account the severity of symptoms, previous treatment, and background characteristics (table) is preferable. Women with mild physiological premenstrual symptoms that have no substantial impact on their functioning may need no more than support and reassurance of normality. Advise good nutrition, exercise, and stress reduction, which are realistic and healthful, albeit unproved, non-medical approaches. A patient who has debilitating symptoms but no symptom-free week may have an underlying psychological, psychiatric, or physical condition that is not related to the ovarian cycle and which is unlikely to be a premenstrual disorder. Explore alternative diagnoses and refer to psychiatric services if necessary. Symptoms of the perimenopause can be similar to the premenstrual syndrome but are also non-cyclical. Women with a premenstrual syndrome-like cycle associated with progestogen treatment may be managed easily by changing type, dose, or duration of the treatment. Consider administration of progesterone via a levonorgestrel releasing intrauterine system. In women whose symptoms are caused by the oral contraceptive, consider changing the pill or changing to an intrauterine system. Women who have substantial premenstrual impairment with only partial relief after menstruation could have an underlying psychological or physical condition with exacerbations related to ovarian function. In such cases consider one of the following approaches. Either treat the underlying condition adequately, in which case the premenstrual phase may become tolerable, or suppress ovulation to reduce luteal phase symptoms to the level of the follicular phase. Psychological interventions and psychotropic agents may achieve both aims simultaneously in these patients or in those with both a psychiatric disorder and premenstrual syndrome.
It is easy to overlook cyclical symptoms in the absence of a reference menstrual bleed. In women who do not menstruate (as a result of hysterectomy, endometrial ablation, or a levonorgestrel releasing intrauterine system) but report a regular pattern of symptoms, measuring progesterone blood concentrations and noting a peak of symptoms will help to show the association between symptoms and ovulation. Manage as for core premenstrual disorder. It will be more difficult to use luteal phase-only treatment without a menstrual cycle as a guide.
Agnus castus (Vitex agnus-castus), also known as Chaste tree and Monk’s pepper, grows in Mediterranean countries and central Asia. The dried fruit, which has a pepper-like aroma and flavour, is used in herbal medicine preparations.
The common name of this pretty herb is Chaste Tree, harking back to the Crusaders’ belief that it would crush their wives’ libidos whilst they were off crusading. Whether it actually achieved this effect is doubtful as it is now recognised as boosting female fertility and easing menstrual symptoms, but the wives obviously weren’t telling and who can blame them? Athenian women used to put the leaves in their beds to help with gynaecological problems, which also sounds rather dubious! Monks, however, used to grind the seeds to make pepper, which was believed to help keep them ‘chaste’, and this is rather more credible as we now use Agnus castus for teenage acne in boys, so it may well balance testosterone levels in men.
The benefits of Agnus castus come from its actions upon the pituitary gland – specifically on the production of a hormone called luteinising hormone (LH), which indirectly increases progesterone production and helps regulate the menstrual cycle. Agnus castus also keeps prolactin secretion in check, which may benefit some infertile women as well as some women with breast tenderness associated with premenstrual syndrome (PMS).
A trial published in the British Medical Journal in 2001 showed Agnus castus to have a beneficial effect on PMS symptoms, ranging from anger and irritability to bloating and breast fullness. The herb was well tolerated and did not cause unwanted side effects.
Another trial published in 2000, showed 42% of the 1,634 women involved reporting that they no longer suffered from PMS! Overall, 93% of the women on the trial reported that their PMS symptoms either disappeared or decreased. Interestingly, 23 of the women on the trial fell pregnant whilst taking Agnus castus and 19 of them had previously had fertility problems. Seemingly, not only does Agnus castus increase progesterone, but it inhibits prolactin high levels of which have been connected to infertility It is therefore well worth trying if you’ve had problems conceiving.
A controlled clinical trial found that women taking 20 mg per day of a concentrated Agnus castus extract for three menstrual cycles had a significant reduction in symptoms of PMS, including irritability, mood swings, headache and breast tenderness. A review of other trials and case reports suggests there is at least preliminary support that Agnus castus should be considered for women with irregular periods, infertility and mildly elevated prolactin levels.
How is it usually taken?
As the dried herb in capsules or as in liquid preparations. Agnus castus is typically taken once in the morning with liquid for several months consecutively.
With its emphasis on long-term balancing of a woman’s hormonal system, Agnus castus is not a fast-acting herb and is unlikely to give immediate relief to the discomfort associated with PMS. For premenstrual syndrome, or frequent or heavy periods, Agnus castus can be used continuously for four to six months. Infertile women with amenorrhoea (lack of menstruation) can remain on Agnus castus for 12 to 18 months, unless pregnancy occurs during treatment.
Are there any side effects or interactions?
Side effects may include minor stomach upset and a mild skin rash with itching. Agnus castus is not recommended for use during pregnancy and should not be used concurrently with hormone therapy (e.g., oestrogen, progesterone).
Premenstrual syndrome - acupuncture
Reuters (10/06/11) Evidence for acupuncture PMS relief is shaky (BJOG mentioned)
©2003 - 2011 Dr Paul Fogarty