Observational Study On Premular - Part 1

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Observational Study On Premular


Menstrual cycle irregularities (MCIs) and the premenstrual syndrome (PMS) are a common disorder in women during their reproductive lifespan. The prevalence for MCIs is about 20% in young women [1]. About 20% - 40% of women suffer from PMS, and 40% - 50% of these women are impaired in their interpersonal and workplace activities [2-5]. The cause of these disorders are still unclear, however current scientific evidence suggests that altered regulation of hormones and neurotransmitters
1Medical practice for Gynecology and Obstetrics, Solothurn; 2Medical practice for Gynecology and Obstetrics, Schaffhausen; 3ClinResearch Ltd., Aesch; 4Max Zeller Soehne AG, Romanshorn, Switzerland
Corresponding author: Dr. med. Roger Eltbogen, Praxis fr Gynkologie und Geburtshilfe, CH-4500 Solothurn, Rossmarktplatz 12; e-mail: eltbogen@hin.ch
such as serotonin and dopamine may be involved in these disorders, and premenopausal mastodynia may be related to latent hyperprolactinemia [6-11]. The majority of women being afflicted with MCIs and PMS self-medicate with over-the-counter (OTC) products such as vitamin and/or mineral supplements and other complementary or herbal products [12].
The fruit of Chaste tree (Vitex agnus-castus L. [VAC]) has been used as a medicinal plant over 2500 years and documented in ancient Egypt, Greece and Rome. Over the past 60 years, VAC extracts has been widely used in Europe for gynaecologic conditions such as PMS and MCIs including polymenorrhea, oligomenorrhea or amenorrhea, as
Treatment of Menstrual Cycle Irregularities with Vitex agnus-castus Extract
J GYNKOL ENDOKRINOL 2015; 25 (2) 10-15
well as cyclical breast discomfort and dysfunctional uterine bleeding [13-16].
The effect of VAC extract on PMS, mastodynia and MCIs has been evaluated in open-label clinical trials conducted as of the late fifties to nowadays. Remission or marked improvements were reported in 60% - 80% of women treated with VAC extract, and similar success rates were observed also in studies with large patient populations [13, 17-23].
Clinical efficacy and safety of VAC extracts have been confirmed in placebo-controlled, randomised clinical trials (RCTs) in women with PMS [24-26]. Placebo-controlled RCTs conducted in women with luteal phase defects and fertility disorders revealed increased concentrations of luteal hormones [28] and number of pregnancies [27, 28].
Treatment with VAC extracts showed clear improvements of symptoms, while the rate of adverse events (AEs) was generally low [14]. A comprehensive review on the safety of VAC extracts evaluated data from clinical studies, post-marketing surveillance programs and spontaneous reporting schemes and confirmed that adverse drug reactions (ADRs) with VAC extract treatment are rare, generally mild and reversible [29].
In the majority of the clinical studies, the treatment period covered three menstrual cycles, but the majority of the authors suggest that continuing for more than three months prevents a recurrence of symptoms, especially since VAC extract was also well tolerated in long-term use [21-23, 30].
The clinical efficacy and safety of herbal drugs underlie some important factors such as the origin of the plants or fruits, the extract manufacturing process and the amount of crude drug that is applied [31, 32]. The VAC extract Ze 440, a dry extract manufactured from the fruits of VAC (extracted by ethanol 60% [m / m]) was used in a RCT and several observational studies [21, 26, 33]. Based on these studies, the European Medicines Agency (EMA) declared the ethanolic VAC extract (60 % m / m) as the only extract with an well-established use status for the treatment of premenstrual syndrome [34]. The effect of various doses of Ze 440 (8 mg, 20 mg and 30 mg) was systematically assessed in a placebo controlled, double-blind study published in 2012 [33]. Treatments with a once daily dose of 20 mg and 30 mg over three menstrual cycles revealed a marked and significantly better relief of symptoms compared to placebo [33].
While the outcomes of recent clinical investigation established the benefit of VAC extracts in PMS, fewer studies were conducted to evaluate the effect on MCIs and specific symptoms such as polymenorrhea, oligomenorrhea and amenorrhea. The objective of this non-interventional, observational study was to evaluate the efficacy and safety of a recommended once-daily dose of 20 mg Ze 440 VAC extract on relief of symptoms related to MCIs and menstrual bleeding in women in primary medical routine care.
n Patients and Methods
This non-interventional, observational study was conducted in Switzerland by 43 physicians in medical routine care in women with menstrual cycle disorders as of October 2009 to October 2011.
It was recommended to physicians to administer one film coated tablet per day containing 20 mg Ze 440 VAC extract (premens, Zeller Medical AG, 8590 Romanshorn, Switzerland) during three menstrual cycles.
Outcome Measures
The primary objective of this NIS was to evaluate the effect of Ze 440 VAC extract on menstrual cycle irregularities (MCIs) overall, and on specific symptoms such as polymenorrhea, oligomenorrhea and amenorrhea. Furthermore, the effect on other symptoms related to menstrual bleeding, including hypermenorrhea, menometrorrhagia, intermenstrual bleeding, ovulation bleeding, and premenstrual and postmenstrual bleeding and dysmenorrhea were evaluated. Assessments were performed at baseline visit (BV) and at a follow up visit (FV) after treatment during three menstrual cycles. Assessment of treatment outcome by physicians, treatment satisfaction by patients and reasons to continue or stop treatment with Ze 440 VAC extract were recorded at the FV and summarised. Spontaneously reported AEs occurring during the treatment period were collected.
Statistical Analysis
To evaluate the outcomes of this NIS clinical data were entered on an oracle database, descriptive statistical analysis using SAS (version 9.2) was performed and change from BV to the FV were analysed.
n Results
Demographics and baseline characteristics
A total of 211 women suffering from MCIs participated in this observational study. The mean age was 35.3 8.8 years (Table 1). The proportion of women with an age <25 years was 12%, between 25 to 39 years was 50% and ≥40 years was 35% (plus 3% not specified). Normal weight was reported in 53% of the women and proportions of females with underweight or overweight are presented in Table 1.
Premenopausal symptoms were recorded in 30% and premenstrual syndrome in 27% of the women (Figure 1). Furthermore, endometriosis, polycystic ovary syndrome and uterus myomatosus, eating disorders or extensive sports were recorded as possible underlying diseases or disorders leading to MCIs and the proportion of participating women affected by these disorders are shown in Figure 1. Out of 211 patients included 53 women (25%) reported an unfulfilled desire to have children.

Author - Dr. med. Roger Eltbogen

Published - 2015-06-29