Description of the condition
Premenstrual syndrome (PMS) is a disorder affecting large numbers of women, characterised by a set of symptoms that occur during the luteal phase of the menstrual cycle. Symptoms disappear by the end of menstruation and do not recur before ovulation, giving a symptom-free interval of at least one week. PMS is cyclical and occurs in most menstrual cycles (O'Brien 2011). PMS is marked by a variety of emotional, physical, and behavioural symptoms. The symptoms typically include irritability, depression, mood swings, bloating, breast tenderness and sleep disturbances (Gianetto-Berruti 2002; Johnson 2004; O'Brien 2003; Panay 2005). A severe form of PMS is known as premenstrual dysphoria or premenstrual dysphoric disorder and was previously known as late luteal phase dysphoric disorder (O'Brien 2011) that causes significant distress and interferes with normal functioning. Studies have reported that as many as 85% of menstruating women would have experienced at least one or more symptoms of PMS (Gianetto-Berruti 2002; Johnson 2004). In about 3 to 10% of women, the symptoms have adverse effects on activities of their daily living and may affect their interpersonal relationships (Gianetto-Berruti 2002; Halbreich 2003; Johnson 2004; O'Brien 2003; Panay 2005; Smith 1995). About 1.5 million women in the United Kingdom experience such severe PMS that greatly reduces their quality of life. Studies have demonstrated deterioration in work effectiveness and cognitive function in women with PMS compared to women without PMS (Johnson 2004; Panay 2005).The precise causation or aetiology of PMS remains unclear. No significant racial or ethnic differences have been shown to exist (Gianetto-Berruti 2002). PMS tends to be more severe among women aged 25 to 35 years old (Johnson 2004). There appears to be a genetic link with PMS risk; monozygotic twins are twice as likely to suffer from PMS as dizygotic twins (Gianetto-Berruti 2002). Similarly, daughters of affected mothers have a 70% greater chance of experiencing PMS than those with unaffected mothers (Gianetto-Berruti 2002). Past history of depressive illness is another significant reported risk factor for PMS (Johnson 2004;Kaur 2004). Previous publications have variably hypothesised that PMS may be associated with excess oestrogen, a deficiency of progesterone or changes in the ratio of oestrogen and progesterone (Gianetto-Berruti 2002). It is now thought that the condition is due to complex interactions between ovarian steroids and neurotransmitters (Rapkin 2007). Although much has been written on diagnostic criteria over the past 30 years, there is no true consensus on which technique is acceptable. A clinical diagnosis requires symptoms to be confirmed by prospective recording for at least two menstrual cycles and that they cause substantial distress or impairment to daily life (e.g. work, school, social activities, hobbies, interpersonal relationships (ACOG 2001; O'Brien 2011). Individual studies have used idiosyncratic techniques, this being true particularly true for older studies. Typically these methods have included visual analogue scales, categorical scales such as Moos' Menstrual Distress questionnaire, Calendar of Premenstrual Experiences and the Daily Record of Severity of Problems. There remains no established consensus but the Daily Record of Severity of Problems has been used in most recent publications.
Description of the intervention
Oestrogen therapy has been proposed as a method for management in PMS through its ability to suppress ovulation and the subsequent endocrine changes of the cycle. Oestrogen can be delivered as oral tablets, transdermal patches, implants, vaginal pessaries, gels and creams. The oestrogens which have been used and studied in the management of PMS include mainly oestradiol in the form of transdermal patches or subcutaneous implants to suppress ovulation in controlled studies (Magos 1986; Smith 1995; Watson 1990). Both routes of administering oestradiol appear to show positive effects for treating mental and physical symptoms .To prevent endometrial hyperplasia, cyclical progestogens are given to ensure a regular withdrawal bleed. The potential oestrogens which may suppress ovulation include natural and synthetic oestrogens including steroids and non steroidal preparations.
How the intervention might work
Though many theories have been proposed, the exact pathway and definitive aetiology of PMS is unknown (O'Brien 2003; Smith 1995; Watson 1990). PMS is probably related to ovulation as symptoms do not occur before the onset of puberty, during pregnancy or after menopause. Menstruation per se is not be necessary for PMS and it can occur after hysterectomy and endometrial ablation as ovarian function is unaffected (Magos 1986). This knowledge has led to use of several ovulation-suppressing drugs. The nature of some of these drugs limits their long-term use because of associated safety issues, thereby also limiting their success. For example, gonadotrophin releasing hormone agonists (GnRH agonist) and danazol have both demonstrated efficacy in alleviating several premenstrual symptoms. Though effective, the use of danazol is limited because of its androgenic side effects and so it cannot be used on a long term basis. GnRH is very effective but long term use is limited by the resulting oestrogen deficient state.
Controlled trials have demonstrated that 17 ß-oestradiol combined with cyclical progestogen (for regular withdrawal periods and to prevent endometrial hyperplasia) administered as an implant or patch is highly effective in controlling PMS symptoms for long term use (Magos 1986; Smith 1995; Watson 1990). Though oestrogen is an effective agent for treating PMS, its use may be limited in individual patients by the need for a progestogen in women with a uterus and because of the subsequent progestogenic/PMS-like side effects. As oestrogen-only treatment has been found to be associated with endometrial hyperplasia/cancer, progestogen therapy is recommended for endometrial protection. The use of local progesterone (Mirena IUS) has now enabled oestrogen to be one of the most effective treatment options for PMS. It is widely used in UK but there are no fully published randomised controlled trials (RCTs). We specifically exclude studies on oral contraceptives (OCs) especially those containing drospirenone as this has been considered as a side issue in another Cochrane review (Lopez 2012).
Why it is important to do this review
Whilst there are several published trials of oestrogen treatment of PMS, there is no existing systematic review evaluating the therapeutic effectiveness of non-contraceptive oestrogen-containing preparations in the management of PMS. Oral contraceptives are not included in this systematic review. A Cochrane review of oral contraceptives has been published but, surprisingly, this focused only on those containing drospirenone and ethinyl oestradiol (Lopez 2012). There is a need for a separate review of all OCs but that is not within the context of the present review.