Treatment of premenstrual syndrome and premenstrual dysphoric disorder

INTRODUCTION — The premenstrual syndrome (PMS) is characterized by the presence of both physical and behavioral symptoms that occur repetitively in the second half of the menstrual cycle and interfere with some aspects of the woman's life. The American Psychiatric Association defines premenstrual dysphoric disorder (PMDD) as a severe form of PMS in which symptoms of anger, irritability, and internal tension are prominent.

The management of PMS and PMDD will be reviewed here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis/differential diagnosis of PMS and PMDD are discussed separately. (See "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder" and "Epidemiology and pathogenesis of premenstrual syndrome and premenstrual dysphoric disorder".)

GENERAL PRINCIPLES — The core symptoms of premenstrual syndrome (PMS) include affective symptoms, such as depression, irritability, and anxiety, and somatic symptoms, such as breast pain, bloating and swelling, and headache. The symptom(s) must impair functioning in some way and the symptom must remit at menses or shortly thereafter. Premenstrual dysphoric disorder (PMDD) is a more severe form. The diagnostic criteria for PMS and PMDD are reviewed separately. (See "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder".)

A clear diagnosis of PMS or PMDD should be established before treatment is considered. In particular, women must be symptom free during the follicular phase. This can be best discerned by having a patient chart her mood and physical symptoms daily over the course of at least one, but ideally two menstrual cycles (figure 1 and table 1). Of note, some women have low-level symptoms throughout the cycle with worsening premenstrually. This likely represents a disorder other than PMS or PMDD, such as dysthymic disorder or major depressive disorder that worsens premenstrually. (See "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder".)

The treatment goals for patients with premenstrual disorders are to relieve symptoms and improve functional impairment. A number of approaches, including lifestyle measures (exercise and relaxation techniques), cognitive behavioral therapy, and medications (selective serotonin reuptake inhibitors [SSRIs] and/or combined oral estrogen-progestin contraceptives (COCs) are effective for women with either PMS or PMDD (table 2).

MILD SYMPTOMS — For women with mild premenstrual symptoms that do not cause distress, economic dysfunction, or social dysfunction, we suggest lifestyle measures such as regular exercise and stress reduction techniques. Although these interventions are not well studied, they may be helpful (algorithm 1).

Exercise and relaxation techniques — Exercise and stress reduction are beneficial in general and should be recommended on this basis. Although not rigorously studied, exercise [1,2] and relaxation [3] may help to alleviate premenstrual syndrome (PMS) symptoms (table 2). Exercise may be particularly helpful for physical symptoms [4]. It is possible that some of the effects of either exercise or relaxation may be the result of attention and placebo effects.

Vitex agnus castus — Vitex agnus castus (chasteberry) is a popular herbal remedy that appears to be an effective treatment option for women with mild premenstrual symptoms. Overall, vitex appears to be more effective than placebo for PMS symptoms, while its efficacy for premenstrual dysphoric disorder (PMDD) is less certain [5]. In a systematic review of vitex extract trials for PMS (n = 8), only two were eligible for meta-analysis because of variability in patient populations, definitions of PMS, vitex dosing, and outcome measures. However, the review and meta-analysis suggests that vitex is well-tolerated and more effective than placebo for a number of PMS symptoms. Two trials in women with PMDD (vitex versus fluoxetine) were also analyzed; fluoxetine was the more effective intervention. However, vitex did show some benefit in one of the PMDD trials. The most common dosing studied is 20 to 40 mg of vitex extract.

Other — A number of vitamins and dietary supplements, including primrose oil, vitamin B6, vitamin E, calcium, and magnesium, have been studied as therapeutic agents for PMS; however, evidence that any of these is more effective than placebo, which has a 30 percent response rate, is inconsistent (table 2) [6-15].

We currently suggest against the routine use of vitamin B6, high doses of calcium supplements, or other vitamins given the low-quality evidence and the potential for harm (peripheral neuropathy with high-dose B6 and an increased risk of renal calculi and possible risk of heart disease with calcium supplementation). (See "Calcium and vitamin D supplementation in osteoporosis", section on 'Side effects'.)

MODERATE TO SEVERE SYMPTOMS

Overview of options — Women who meet the criteria for premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) including economic or social dysfunction are best served by pharmacologic or behavioral interventions such as cognitive behavioral therapy (algorithm 1 and table 2) (see 'Cognitive behavioral therapy' below). However, before initiating therapy, other conditions with symptoms that can overlap with PMS/PMDD should be ruled out, including depression or anxiety disorders, substance abuse, and hypothyroidism. (See "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder", section on 'Differential diagnosis'.)

The two main approaches for initial pharmacotherapy of moderate to severe PMDD include (algorithm 1):

●Targeting the serotonin system by increasing central serotonergic transmission (selective serotonin reuptake inhibitors [SSRIs]). Of all the treatment options for PMDD, SSRIs have the best evidence for efficacy. (See 'Selective serotonin reuptake inhibitors' below.)

●Suppressing the hypothalamic-pituitary-ovarian axis to abolish cyclic changes in gonadal steroids (combined estrogen-progestin oral contraceptives [COCs], gonadotropin-releasing hormone [GnRH] agonists). This is typically reserved for women who have severe symptoms that have not responded to other treatments. COCs may ameliorate PMS symptoms in general, but they are not better than placebo at decreasing depressive symptoms experienced premenstrually [16]. (See 'Other therapies' below.)

●In women for whom contraception is not a high priority, we discuss SSRIs first. On the other hand, if the patient does not have impairing depressive symptoms and contraception is a high priority, we discuss combination estrogen-progestin contraception first, although some women may require both a contraceptive agent and SSRIs. (See 'Combined estrogen-progestin contraception' below and 'Selective serotonin reuptake inhibitors' below.)

Women who do not desire contraception

Selective serotonin reuptake inhibitors — Because of their proven efficacy and safety profile, we recommend SSRIs for women with premenstrual symptoms that include socioeconomic dysfunction that have been documented prospectively and who do not desire hormonal contraception (algorithm 1). (See 'Moderate to severe symptoms' above and "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder", section on 'Prospective monitoring with self-rating scale'.)

Clinical trials [17-22] and systematic reviews [23,24] of SSRIs for PMS and PMDD conclude that these medications are effective. We typically start sertraline, citalopram, escitalopram, or fluoxetine, as these are extensively studied. Paroxetine is also effective but is more likely to be associated with weight gain. (See "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects", section on 'Weight change'.)

A beneficial effect can be expected in the first cycle. If response is suboptimal, the dose can be increased in the subsequent cycle. SSRI therapy appears to be more effective for mood symptoms than somatic symptoms [13]. There are no strong predictors of response to SSRIs in women with PMDD.

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is also more effective than placebo for PMDD [25,26], but we suggest SSRIs as first-line therapy because venlafaxine is associated with discontinuation symptoms that can be worse than those seen with SSRIs. (See "Serotonin-norepinephrine reuptake inhibitors: Pharmacology, administration, and side effects", section on 'Venlafaxine'.)

A tricyclic antidepressant, clomipramine (given either throughout the menstrual cycle or restricted to the luteal phase), is also more effective than placebo, but we do not suggest its routine use, because of its side effects (sedation, dry mouth, and weight gain) [27,28]. If it is used, the starting dose should be 25 mg/day, titrating up to 150 to 200 mg at bedtime.

Regimens — There are three SSRI regimens for the management of moderate to severe symptoms: continuous daily administration, luteal-phase therapy, or symptom-onset therapy. The choice of regimen depends upon the pattern and duration of symptoms (including their predictability) and patient preference. (See 'Choosing a regimen' below.)

Continuous — SSRIs are effective for premenstrual symptoms whether taken continuously or intermittently [29]. We suggest continuous administration for women with low-level symptoms present during non-premenstrual intervals. In addition, some women choose this approach over intermittent regimens for convenience and simplicity. If a woman has severe physical symptoms, continuous dosing regimens appear more effective than intermittent regimens [24]. (See 'Choosing a regimen' below.)

Luteal phase therapy — Many women prefer the luteal phase-only regimen, which is started on cycle day 14 [30]. Therapy is typically discontinued at the onset of menses, although it may be continued for several additional days in women with a history of persistent symptoms during menses. This regimen has the advantages of being less expensive and having fewer side effects. Individual trials [28,31-33] and a meta-analysis [24] have reported that SSRIs are equally effective for symptom relief whether taken continuously or only in the luteal phase.

For a woman who chooses this regimen, it is important to ensure that she is asymptomatic during the follicular phase of the cycle as she will otherwise be undertreated. Higher doses of the SSRI are needed in some women receiving luteal phase therapy to adequately treat physical symptoms [34,35]. (See 'Choosing a regimen' below.)

Symptom-onset therapy — Intermittent therapy beginning at the point of symptom onset until the first few days of menses is effective [36]. In a randomized trial, symptom-onset therapy was more effective than placebo [37]. (See 'Choosing a regimen' below.)

Choosing a regimen — Deciding whether treatment should be offered continuously throughout the menstrual cycle, during the luteal phase only, or at symptom onset depends on a number of factors: (1) clinician assessment that symptoms are present only during the premenstrual phase of the menstrual cycle versus throughout the menstrual cycle with premenstrual worsening, (2) patient preference, and (3) predictability of symptom expression.

●For women with low-level symptoms present during non-premenstrual intervals or with severe physical symptoms, we suggest daily treatment throughout the menstrual cycle.

●For women with longer intermenstrual intervals, continuous treatment is best since the onset of symptoms may be unpredictable.

●For women with predictable symptoms that endure for more than a week before the onset of menses, we suggest a luteal phase regimen.

●For women with symptoms for a week or less who can easily recognize symptom onset, we suggest symptom-onset therapy.

●If intermittent treatments are ineffective or difficult for patients to follow, continuous treatment should be offered (algorithm 1).

Dosing — In general, doses used for PMDD are similar to those used for the treatment of depression. An example of dosing for SSRI regimens in the management of PMDD is shown for citalopram:

●Continuous daily dosing regimen – The initial dose in cycle one is 10 mg daily. The dose may be increased over the first month as needed to 20 mg daily. In subsequent menstrual cycles, further dose increases (eg, in 10 mg increments per menstrual cycle) up to a maximum of 40 mg/day are sometimes necessary (table 3) [31].

●Intermittent regimens

•Luteal phase dosing regimen – The initial dose in cycle one is 10 mg daily starting on day 14 and continued until the onset of menses. If needed, the dose can increased over the first month to usual effective dose of 20 mg daily. In a subsequent cycle, a further increase to a maximum dose of 30 mg/day during the luteal phase is sometimes necessary for optimal response [31]. Of note, we use a maximum dose of 40 mg/day for continuous regimens, but only 30 mg/day for intermittent regimens (table 3).

•Symptom-onset dosing regimen – The initial dose in cycle one is 10 mg daily beginning the day of symptom onset until a few days after the start of menses; over the first month, the dose may be increased as needed to usual effective dose of 20 mg daily. In subsequent menstrual cycles, a further increase to the maximum intermittent regimen dose (30 mg/day) is sometimes necessary for symptom control (table 3).

The suggested dosing for other SSRIs is found in the table (table 3). When starting therapy, most patients may tolerate the medication better by starting with the minimum effective dose, for example: fluoxetine 10 mg, sertraline 25 mg (or even 12.5 mg), paroxetine 10 mg, citalopram 10 mg, and escitalopram 5 to 10 mg (table 3).

For some women, increasing the SSRI dose during the luteal phase is more effective than a continuous dose throughout the cycle [38].

Adverse effects

●Common side effects – Side effects of SSRIs are dose dependent, occur in approximately 15 percent of patients, and are the most common reason for discontinuing treatment. These include nausea, headache, insomnia, and decreased libido [24,37]. Nausea, the most common side effect, usually resolves within four to five days and does not recur if treatment is given intermittently (luteal phase only). To minimize side effects, we suggest initiating therapy with a low dose and increasing as needed. (See 'Dosing' above.)

●Sexual side effects – The most problematic side effect of an SSRI may be sexual dysfunction, including diminished sexual interest, delayed orgasm, and anorgasmia. A dose reduction may not alleviate this side effect. Women should be informed that this complication may arise. Sexual function recovers after therapy is stopped. Intermittent (luteal phase) treatment may reduce these side effects. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management".)

●Discontinuation symptoms – Continuous daily (but not intermittent administration) of sertraline, paroxetine, and venlafaxine for several months followed by sudden treatment discontinuation can lead to discontinuation symptoms such as dizziness, ringing of the ears, and mild "body shocks." These withdrawal symptoms are most severe with venlafaxine, a drug we do not suggest to be a first-line agent. Women should be informed of this possibility and tapered from medication if possible [39].

Response to therapy — Up to 60 to 70 percent of symptomatic women respond to an SSRI, but 30 to 40 percent of women do not respond. There are no strong predictors of response to SSRIs in women with PMDD.

A beneficial effect can be expected in the first cycle. Some women who do not respond to or tolerate one SSRI may respond to or tolerate a second SSRI, so it is worth attempting this switch in nonresponders (algorithm 1). Additionally, women who do not respond completely to luteal phase therapy may benefit from daily therapy, and some women whose response is not optimal to continuous treatment may do better with luteal phase treatment.

Symptomatic improvement — As noted, 60 to 70 percent of women with PMDD respond to an SSRI. If continuous SSRI is difficult to tolerate, the patient could try luteal phase-only treatment.

No improvement — If response is suboptimal, the dose can be increased in the subsequent cycle. However, lack of response should not be diagnosed until there is no effect after several menstrual cycles of treatment. SSRI therapy appears to be more effective for mood symptoms than somatic symptoms [13].

If the SSRI is ineffective, we suggest that women next try a different SSRI (algorithm 1 and table 2). If a second SSRI is ineffective, we often try a third SSRI before moving to a second-line therapy. In addition, if multiple SSRIs have been ineffective, we suggest additional evaluation to ensure that another illness, such as major depression, a substance use disorder, or another condition, has not been missed. (See 'Combined estrogen-progestin contraception' below and 'Other therapies' below.)

Duration of therapy — The optimal duration of therapy is unknown. We often continue therapy for one year and then discuss either a taper and discontinuation of medication or a trial of intermittent therapy. For women on intermittent therapy, they can try to stop therapy. Recurrence of symptoms is an indication that treatment should be resumed. Women with recurrent symptoms typically need treatment until they become pregnant or complete the menopausal transition.

Women who desire contraception

Combined estrogen-progestin contraception — For women with moderate to severe nondepressive symptoms who are interested in hormonal contraception, we suggest treatment with a COC (algorithm 1). This is the simplest way to suppress the hypothalamic-pituitary-ovarian axis and ovulation. We prefer monophasic pills, as multiphasic preparations can worsen mood symptoms.

Drospirenone-containing COCs (in particular those with a shortened pill-free interval; four rather than seven days) are effective and approved for the management of PMDD [40]. We typically start with a 3 mg drospirenone (DRSP)/20 mcg ethinyl estradiol (EE) COC. If PMDD symptoms persist and/or there is breakthrough bleeding that does not resolve after three months, we increase to a 3 mg DRSP/30 mcg EE COC. If PMDD symptoms do not resolve on the higher estrogen dose, drospirenone-based COC, we often suggest a trial with a hormonal COC that is continuously administered. In addition, women with PMDD who initiate COCs should be monitored as some may experience mood worsening with COC treatment [41]. If symptom relief with the COC monotherapy is incomplete, an SSRI can be added. (See 'Selective serotonin reuptake inhibitors' above.)

Randomized trials [40,42] and a meta-analysis [43] suggest that a 20 mcg EE/3 mg DRSP COC with a four-day pill-free interval is more effective than placebo for reducing the symptoms of PMDD. However, in the meta-analysis, a large placebo effect was seen (36 percent reduction in PMDD symptoms with placebo compared with 48 percent with the COC) [44]. Other COCs may be effective, but they have not been well studied. In one meta-analysis of nine trials, COCs improved overall symptoms, but not depression symptoms of PMS/PMDD, when compared with placebo [16].

Although we sometimes suggest continuous use of a combined COC, data for this approach are somewhat limited [45-47]. One study observed no benefit of continuous COCs on PMDD when compared with placebo or a cyclic COC [46]. In contrast, in an analysis of four trials (three randomized, one open-label) of a continuous COC 20 mcg EE/90 mcg levonorgestrel (LNG), an overall reduction in PMS and PMDD symptoms was seen compared with placebo [45]. Women taking the continuous COC experienced higher rates of vaginal bleeding than the placebo groups (as has been observed in most trials of continuous COCs). This analysis was limited by inconsistent results across trials and a large placebo effect. In spite of these limitations, continuous administration of an LNG/EE COC is a reasonable option for women with PMDD who have not responded to other treatment options such as a COC with drospirenone and a shortened hormone-free interval. Continuous COCs with progestins other than levonorgestrel have not yet been studied.

Of concern, drospirenone may be associated with a higher risk of venous thromboembolism (VTE) than some other progestins. In 2012, the US Food and Drug Administration (FDA) added revised labeling to COCs containing drospirenone, stating that they may be associated with a higher risk of VTE when compared with levonorgestrel and some other progestins. The FDA currently does not advise women to stop drospirenone-containing COCs, but it does suggest that an individual's risk of VTE be assessed before starting one in a new COC user. Lastly, the warning notes that the VTE risk with drospirenone is small and still lower than the risk of VTE during pregnancy. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Cardiovascular effects'.)

Other therapies — A number of other medications have been used when either SSRIs and/or COCs are only partially effective, ineffective, or difficult to tolerate. If the patient is suffering from severe PMDD not complicated by other illnesses and not responsive to any SSRIs, we suggest other therapies (table 2).

Cognitive behavioral therapy — Cognitive behavioral therapy (CBT) may provide some benefit for women with PMDD. A meta-analysis of five randomized trials observed a reduction in symptoms of anxiety and depression with CBT compared to other interventions [48]. Other studies have reported a reduction in symptom intensity and distress [49], as well as an improvement in coping skills [50]. For women with moderate to severe symptoms with a suboptimal response to pharmacologic treatment, the addition of cognitive behavioral therapy may be beneficial. (See "Overview of psychotherapies", section on 'Cognitive and behavioral therapies'.)

GnRH agonists — In women with severe symptoms who have not responded to or cannot tolerate SSRIs or COCs, we suggest gonadotropin-releasing hormone (GnRH) agonist therapy with low-dose estrogen-progesterone "add back" therapy as the next step (algorithm 1 and table 2). However, GnRH agonists should not be considered until the patient has first tried multiple SSRIs and a COC with a shortened pill-free interval or continuous administration.

The contributory role of ovarian steroids in the pathogenesis of PMDD led to the evaluation of GnRH agonists in this disorder . The first demonstration of benefit of "medical oophorectomy" with a GnRH agonist in the treatment of PMS was made in a crossover study of eight patients [51]. This finding has subsequently been replicated by several other investigators [52,53]. (See "Epidemiology and pathogenesis of premenstrual syndrome and premenstrual dysphoric disorder".)

GnRH agonist therapy alone is effective for PMDD [54]. However, GnRH agonists should not be given without estrogen-progestin add-back therapy to avoid menopausal symptoms and estrogen-deficiency complications such as bone loss. We typically start with leuprolide acetate 3.75 mg depot monthly injection. (See "Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists".)

The side effects with GnRH agonist when administered alone are related to hypoestrogenism and are substantial (in particular, hot flashes and loss of bone mineral density [BMD]) [55]. The long-term use of GnRH agonists is possible with estrogen-progestin add-back, with no loss of BMD and with continued resolution of symptoms [56,57]. Data suggest that the addition of estrogen and progestin does not diminish the efficacy of leuprolide for PMDD [54,58,59]. However, it is essential that estrogen and progestin be given in a continuous regimen and not in a cyclic fashion, which may reproduce PMS.

For add-back therapy, we suggest continuous daily administration of low-dose estradiol. A commonly used regimen is daily oral estradiol (1 mg) plus oral micronized progesterone (100 mg). These doses are similar to those used for menopausal hormone therapy. Equivalent doses of other estrogens or progestins may also be used (estrogen equivalents: oral estradiol 1 mg = transdermal estradiol 0.05 mg = oral conjugated estrogen 625 mg; progestin equivalents: oral micronized progesterone 100 mg = oral medroxyprogesterone acetate 2.5 mg). Some women may experience PMS symptoms from the progestin add-back, in which case dose adjustments are necessary. (See "Preparations for menopausal hormone therapy", section on 'Dose equivalents'.)

In some reports, GnRH agonists were less effective for depressive symptoms than for irritability or physical symptoms [53,60]. However, in one of the authors' experience with GnRH agonists, this is not the case.

Acupuncture — Data on the efficacy of acupuncture for the treatment of women with PMS and PMDD are limited [61,62]. However, a systematic review of three trials of acupuncture versus sham acupuncture suggests that it may improve both mood and physical symptoms (a 17 and 20 percent absolute reduction when compared with sham acupuncture) [63]. However, there was insufficient evidence to determine if there was a difference in the rate of adverse events, and acupuncture has never been compared with standard therapies, such as SSRIs. Therefore, we do not suggest its routine use.

Surgery — Medical therapy of PMDD is usually successful. As a result, surgery (bilateral oophorectomy/bilateral salpingoophorectomy [surgical menopause]) is considered only as a last resort (eg, in the very rare refractory cases with severe, disabling symptoms). Three observational studies found bilateral oophorectomy, usually with concomitant hysterectomy, to be effective for such patients [64-66].

The following guidelines should be considered before resorting to a surgical approach to treatment [67]:

●The diagnosis of PMDD must be confirmed with prospective symptom recording

●GnRH agonist therapy must be the only medical approach that has been effective, and it must have been continuously effective for a minimum of six months

●Tolerance of estrogen (or estrogen-progestin) replacement therapy has been tested during the GnRH agonist therapy

●Childbearing is complete

●The need for several more years of therapy is anticipated based on the woman's age

Not recommended: Alprazolam — Benzodiazepines, in particular, alprazolam, have been used in the past as adjunctive therapy for women with PMDD. However, we agree with the International Society for Premenstrual Disorders and do not suggest the use of alprazolam for PMDD [68]. Although it may have some benefit when compared with placebo [69], the risks of potential misuse outweigh the benefits. (See "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Sedatives-hypnotics' and "Benzodiazepine use disorder".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of premenstrual dysphoric disorder".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) (The Basics)")

●Beyond the Basics topics (see "Patient education: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Core symptoms of PMS and PMDD – The core symptoms of premenstrual syndrome (PMS) include affective symptoms (such as depression, irritability, and anxiety) and somatic symptoms (such as breast pain, bloating and swelling, and headache). The symptom(s) must impair functioning in some way and must remit at menses or shortly thereafter. Premenstrual dysphoric disorder (PMDD) is a more severe form. (See 'General principles' above and "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder".)

●Diagnosis – A clear diagnosis of PMS or PMDD should be established before treatment is considered. In particular, women must be symptom free during the follicular phase. This can be best discerned by having a patient chart her mood and physical symptoms daily over the course of at least one but ideally two menstrual cycles. (See 'General principles' above and "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder".)

●Management

•Mild symptoms – For women with mild premenstrual symptoms that do not cause distress or socioeconomic dysfunction, we initiate targeted behavioral therapy and/or lifestyle measures such as regular exercise and stress reduction techniques (algorithm 1). (See 'Mild symptoms' above.)

A course of cognitive behavioral therapy (CBT) may be beneficial for some women. However, this approach has not yet been studied well, and identifying clinicians who can provide this treatment can be difficult. (See 'Cognitive behavioral therapy' above.)

•Moderate to severe symptoms – We suggest selective serotonin reuptake inhibitors (SSRIs) as our first-line options for women with moderate to severe premenstrual symptoms, especially for those who experience depressive and anxious symptoms (algorithm 1 and table 3) (Grade 2B). SSRIs can be administered as a continuous daily therapy, luteal phase-only treatment (starting on cycle day 14), or symptom-onset therapy, but one must be sure that the patient is asymptomatic during the follicular phase to avoid undertreatment (table 3). (See 'Regimens' above and 'Selective serotonin reuptake inhibitors' above.)

If contraception is the patient’s top priority (in addition to treating the premenstrual symptoms), many women prefer to try a combined estrogen-progestin oral contraceptive (COC) rather than an SSRI as first-line therapy (algorithm 1). We typically use a COC containing drospirenone with a four-day pill-free interval as our first-line pill. If symptom relief with a monophasic COC with a shortened pill-free interval is inadequate, an SSRI can be added. Again, amelioration of depressive and anxious symptoms may be inadequate with COC only treatment (See 'Combined estrogen-progestin contraception' above.)

•Refractory symptoms – For women who have not responded to or cannot tolerate SSRIs or COCs and continue to experience severe symptoms, we typically initiate a trial of gonadotropin-releasing hormone (GnRH) agonist therapy with estrogen-progestin add-back (algorithm 1). (See 'GnRH agonists' above.)

Medical therapy of PMDD is usually successful. As a result, surgery is considered only as a last resort (eg, in cases with severe, disabling symptoms that have responded to GnRH agonist and hormone add-back therapy for at least six months). Guidelines that must be met before considering oophorectomy are outlined above. (See 'Surgery' above.)