Approach

The goal of treatment is to provide relief of symptoms during the luteal phase and to improve quality of life and reduce distress for women with PMS or PMDD. Treatment strategies should be individualized to each woman based on her specific symptoms and their severity. Consider all modalities including lifestyle modifications, psychosocial interventions, and pharmacologic interventions. Many patients will benefit from a multimodal approach.[1]​ Oophorectomy should be reserved for the most resistant and severe symptoms, after full informed consent and shared decision making. Treatment should reflect evidence-based recommendations.

There are no formal criteria available for defining mild, moderate, or severe PMS, and severity is usually based on clinical judgment. Contributing factors include the patient's perception of symptom severity, impact on the patient's quality of life, and the presence or absence of distress or socioeconomic dysfunction.

Several scoring tools are available, the most commonly used being the Daily Record of Severity of Problems (DRSP). Although the DRSP has been validated, there are no cut-off values that have been used to clinically differentiate between symptom severity, and PMS/PMDD studies have set thresholds for the clinical significance of symptoms at different ratings on the DRSP.[56][60]

Exercise, weight, and relaxation

Exercise and relaxation techniques are frequently recommended, but lack robust evidence regarding effectiveness. Some studies have demonstrated benefit, but only low-quality evidence is available in PMS/PMDD versus premenstrual symptoms.[61] Based on overall health benefits, these modalities can be endorsed as initial treatment for mild symptoms or as an adjunct for women with more severe symptoms.[1]​ Lack of evidence for efficacy should be disclosed to the patient. 

Aerobic exercise to decrease both physical and emotional symptoms has been suggested, but data are limited.[62][63][64] One 2018 controlled study of 65 women suggested exercise improved the physical, but not the emotional, symptoms of PMS.[65] One meta-analysis concluded that 45-60 minutes' exercise, of any intensity, performed ≥3 times per week, may provide a clinically significant reduction in menstrual pain.[66]

Yoga improved both physical symptoms and overall sense of well-being in a study of 64 women, 90% of whom reported menstrual pain, but not necessarily PMS/PMDD symptoms. There was no comparator in this study.[67]

The relationship between body mass index (BMI) and PMS/PMDD also remains uncertain. Some studies suggest a relationship between higher BMI (>30.0 or ≥27.5) and PMS/PMDD.[7][68] One prospective study compared 1057 women ages 27-44 years who were free from PMS at baseline but who developed PMS during the study follow-up period (10 years) with 1968 controls.[68] The study found that as BMI increased, so did the incidence of PMS, although symptoms were mostly physical, not emotional, in nature. Each 1 kg/m² increase in BMI was associated with a significant 3% increase in PMS risk. However, another study of 476 females age 18 years suggested that it is not overall BMI, but more complex parameters of body composition such as fat mass, fat-free mass, and total body water, that are associated with risk of PMS.[69]

Diet and vitamin/mineral supplementation

A luteal-phase diet high in complex carbohydrates has been considered helpful to control PMS/PMDD symptoms via the proposed mechanism of increasing tryptophan and ultimately serotonin levels, though data are limited. The only randomized studies that showed this effect over placebo used beverages with combined simple and complex carbohydrates.[3]

Calcium supplementation was found to be better than placebo at improving physical and emotional symptoms of PMS (48% reduction in total symptom scores from baseline compared with a 30% reduction in placebo) in randomized trials.[70][71] Attention should be paid to the maximum dose as calcium may cause constipation; interfere with absorption of medications, vitamins, and minerals; and contribute to kidney stones.

Pyridoxine (vitamin B6) may be offered in select cases, but toxicity (which may include symptoms of sensory neuropathy) may occur with doses as low as 200 mg/day. Symptoms that do not respond should not prompt an increase in dosage. Meta-analyses recognize that most pyridoxine studies are of poor quality, with inconsistent results.[72] Similarly, primrose oil, magnesium, and vitamin E typically show little evidence of benefit over placebo.[71] Studies of zinc supplementation vary, with some studies showing no change over placebo and others suggesting relief after 3 months of therapy.[28][73] Some authors recommend treating with supplements only if deficiencies are documented, although current guidelines do not support this position.

One 2018 meta-analysis looking at the relationship between alcohol consumption and PMS found alcohol intake was associated with a moderate increase in the risk of PMS, and heavy drinking (average of ≥1 ethanol drink/day) yielded a larger increase. The study estimated that eliminating alcohol might reduce 1 in 12 cases of PMS in areas with high alcohol intake such as Europe and the US. The authors postulate that alcohol may be related to PMS by altering levels of sex steroid hormones and gonadotropin during the menstrual cycle, or by a more direct effect on serotonin and gamma-aminobutyric acid (GABA) activity.[30] Further studies are needed to better demonstrate this relationship as well as the impact on alcohol cessation and PMS symptoms.

Cognitive behavioral therapy (CBT)

CBT was shown to be as effective as fluoxetine alone or fluoxetine combined with CBT (primary end point premenstrual scores on the Calendar of Premenstrual Experiences [COPE] and percentage of PMDD cases [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision {DSM-5-TR} diagnostic criteria] in one study).[74] Fluoxetine was associated with more rapid improvement in symptoms, but the effects of CBT appeared to be more persistent than those of fluoxetine.

One systematic review assessed the effect of CBT on behavioral and somatic symptoms.[75] Overall, CBT appears to be an important component of a care plan, alone or in combination with other treatments, in women with PMS/PMDD. The likelihood of bias in studies was considered to be high.

US and UK guidelines recommend that CBT should be considered routinely as a treatment option in PMS.[1][7]​​​​

In one randomized controlled trial, CBT for couples (two sessions while on a waiting list for individual CBT with wait-list control) showed improvement over no treatment. Additionally, couple CBT showed benefit in partner understanding and post-counseling relationship over individual CBT. Triangulation of quantitative and qualitative outcome measures was used to evaluate changes before and after intervention, which included questionnaires and semi-structured one-to-one interviews.[76]

Pharmacologic approaches

Pharmacologic approaches include treatments to suppress ovulation or manipulate hormones, or medications aimed to treat the symptoms of PMS/PMDD. The former include combined oral contraceptives (COCs), transdermal estrogen (with progestin add-back), progestin-only therapies, or gonadotropin-releasing hormone (GnRH) agonists, while the latter include selective serotonin-reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), anxiolytics, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs).

Pharmacologic therapies are recommended for patients with moderate to severe symptoms. (COCs may, however, be used as a second-line option after lifestyle interventions for patients with mild symptoms.) Treatment should be tailored to the predominant symptoms presented by the patient. Some treatments are more suitable for treatment of somatic symptoms and some are more suitable for the behavioral aspects. Combined therapies can be used for mixed symptoms or in the refractory patient.

First-line pharmacologic therapies

  • COCs:

    • Used if contraception is desired.

    • COCs containing drospirenone plus ethinyl estradiol may help treat premenstrual symptoms in women with severe symptoms. One Cochrane review, however, reported that the evidence base is limited and found evidence of a strong placebo effect.[77][78] [ Cochrane Clinical Answers logo ] ​​ Most research has focused on drospirenone-containing formulations and the only COC that is approved for the treatment of PMDD among patients seeking contraception is a drospirenone-containing preparation.[1] However, other COC formulations have also been associated with a reduction in symptoms. Continuous administration is thought to be key to symptom relief (rather than the type of progestin used).​ ​​​​​

    • COCs can be prescribed continuously if a 4-day interval does not alleviate symptoms, although breakthrough bleeding can limit this option. This regimen has been shown to be superior to placebo with a levonorgestrel-containing pill.[79]

    • Monophasic pills may be more effective than multiphasic preparations on mood symptoms.

    • Women should be informed of the small increased risk of thromboembolic events with drospirenone, but this risk is not a contraindication to its use.[80]

    • Although the contraceptive patch and vaginal ring have the same mechanism of action as COCs, research is needed to confirm whether these methods are associated with a reduction in premenstrual symptoms.[1]​​

  • SSRIs/SNRIs:

    • Have been shown to be effective for moderate to severe symptoms of PMS/PMDD, and are often recommended as first-line therapy.[81] [ Cochrane Clinical Answers logo ] ​​​ SSRIs can be used if COCs are contraindicated or if contraception is not desired.

    • SSRIs have a rapid onset of action in the treatment of premenstrual symptoms and can start to improve symptoms within days.[1]

    • Due to the quick treatment response, SSRIs are effective whether given continuously through the month or limited to the luteal phase. Some women start treatment with the onset of symptoms, and this option may be considered, especially in women with irregular cycles. A low starting dose is recommended; a higher dose may be prescribed if there is no response.[7] Limited evidence suggests that continuous and intermittent dosing regimens have comparable efficacy.[1]​​

    • SSRIs are considered to be more effective for behavioral symptoms than for physical symptoms of PMS/PMDD, although improvement in swelling/bloating and breast tenderness was reported in one review.[82]

    • Fluoxetine and sertraline are most frequently prescribed as first-line agents. Lack of response may necessitate an increased dose or a switch to a different drug. Switching from an intermittent to a continuous dosing regimen may be helpful, especially for patients who forget to take their medication as directed.[1]​ In continuous users with persistent symptoms, increasing the dose during the luteal phase has been suggested.[1][83]​​​ Citalopram and escitalopram are well studied in PMS/PMDD.[81] Paroxetine is also effective, but may be more likely than other SSRIs to cause weight gain.

    • Relapse rate is high among patients who discontinue SSRI treatment for premenstrual disorders, and most patients will likely need to continue treatment until menopause.[1]

    • SNRIs, such as venlafaxine, have also been shown to be effective for PMS/PMDD, and may be a good choice for women with low energy symptoms. Withdrawal symptoms from SNRIs may be worse than those from SSRIs.

    • SSRI and SNRI dosing for PMS/PMDD is similar to that for depression, but adverse effects may impact upon tolerance. About 30% to 40% of women do not respond to SSRIs/SNRIs; there are no strong predictors of response.[84]

    • Sexual difficulty and sexual distress have been reported to be present in women who have PMS/PMDD.[85] As SSRIs have sexual adverse effects, the choice of agent may be impacted by preexisting sexual problems, or modified if these adverse effects develop. Changes in sexual function and libido typically last for as long as treatment is continued.[1]

Second-line pharmacologic therapies

  • Transdermal estradiol:

    • Evidence for the treatment of PMS/PMDD with estradiol is limited. Studies have demonstrated improvement of symptoms using transdermal estradiol patches, citing ovulation suppression as the mechanism of action.[86]

    • Protection of the endometrium with a progestin is required with this treatment strategy. As ovulation suppression is not complete, this does not provide birth control. The RCOG recommends that in women with a uterus, the use of continuous estradiol requires the addition of a cyclical progestin for 10-12 days per cycle. This can be given either orally or vaginally with micronized progesterone, which is potentially the least likely to exacerbate symptoms compared with other progestins.[7] This strategy has not been recommended in the US.[1][87]​​​ Adding cyclic progestin to transdermal estradiol patches does not provide contraception.

    • The levonorgestrel-containing intrauterine device provides both endometrial protection and birth control. Systemic absorption in the first 3-4 months will negatively impact some women. However, there are no studies looking at the use of transdermal estrogen with a levonorgestrel-containing intrauterine device in the treatment of PMS/PMDD. One Cochrane review found low-quality evidence to support the effectiveness of continuous estrogen (transdermal or subcutaneous implants) plus a progestin, with a small to moderate effect size. The review included three studies that compared continuous estrogen (plus a progestin) versus placebo with a favorable outcome, but noted that these studies were of poor quality and had a high attrition rate. Some studies also showed worsening of symptoms.[88]

Third-line pharmacologic therapies

  • GnRH agonists:

    • Can be considered if SSRIs and COCs are unsuccessful or are not tolerated in women with severe symptoms of PMS/PMDD.[1]​ It is vital to exclude pregnancy and to investigate unexplained vaginal bleeding before use.

    • The benefit of GnRH agonists for PMS/PMDD has been well demonstrated, but there is a risk of bone loss with treatment. Add-back therapy with an estrogen and a progestin is advised when there are severe symptoms such as hot flashes, or after 6 months of treatment.[1][7]​​​ Daily oral or transdermal estradiol, plus oral or vaginal micronized progesterone, may be used.

    • Tibolone in combination with a GnRH agonist was used successfully in one study compared with placebo.[89]

    • If PMS symptoms resume with progestin add-back, different preparations or regimens should be tried. Long-term treatment is possible if add-back therapy is given. Add-back therapy does not seem to interfere with the effectiveness of treatment.[90]

    • Some authors recommend monitoring of bone density, with discontinuation of treatment when there is documented bone loss.[7]

    • Calcium and vitamin D supplementation should routinely be recommended in women undergoing long-term GnRH treatment.

Surgical treatment

Surgical oophorectomy (with or without hysterectomy) should be reserved for severe refractory disorders that have failed other treatment options, and usually after establishing symptom relief with a 3- to 6-month trial of a GnRH agonist. GnRH agonist treatment is recommended preoperatively as a test of cure and to ensure that hormone replacement therapy is tolerated.[1][7]​​​​

Careful counseling regarding risks and benefits of both surgery and postoperative hormonal therapy should occur prior to any surgical intervention. Childbearing must be complete, and several years of benefit anticipated to warrant this intervention.

Good outcomes have been reported even with postoperative estrogen treatment.[38]

Other therapies

Anxiolytics

  • Anxiolytics, specifically alprazolam, have been used by some clinicians in women with no response to, or as an adjunct to, SSRIs.[91]

  • If a healthcare provider feels alprazolam is warranted, treatment should be limited to only the 2-3 days of the worst symptoms, with careful monitoring of use.

  • The International Society for Premenstrual Disorders does not consider benzodiazepines to be an evidence-based treatment for PMDD and recommends against their use.[3]

Diuretics

  • Spironolactone can be used for physical symptoms such as bloating and mastalgia.

  • Spironolactone should not be given in conjunction with a drospirenone-containing COC due to a theoretical risk of hyperkalemia, although this has not been observed when this combined treatment is used for acne.[92]

NSAIDs

  • NSAIDs can be used to treat dysmenorrhea in patients with mild to severe symptoms, usually in conjunction with other therapies for PMS/PMDD.[1]​

Bromocriptine/cabergoline

  • Bromocriptine or cabergoline may be considered for treating premenstrual mastalgia. Cabergoline appears to be as effective as bromocriptine, with a better adverse-effect profile.[93]

  • There is no evidence demonstrating the efficacy of either bromocriptine or cabergoline for PMS/PMDD.

Alternative therapies

The most promising herbal remedy seems to be Vitex agnus-castus extract, shown to be effective versus placebo in at least one study.[7] ACOG guidelines advise that further study is needed before a recommendation can be made about the use of this treatment in the management of patients with PMS/PMDD.[1]​ Ginkgo biloba has mixed results, and Hypericum perforatum (St. John’s wort) has some benefit.[40][94][95]

Studies are limited by small numbers. With any herbal supplement, quality and consistency of preparation remains a concern in advising their use.

Limited evidence suggests that acupuncture may be of modest benefit for the management of PMS/PMDD and ACOG guidelines advise that it can be included as part of a holistic treatment approach in patients with premenstrual symptoms.[1][95][96]​​​​ Many studies are methodologically flawed; rigorous trials are required.

Small studies show a benefit of reflexology over placebo.[97][98][99]

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