To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome.
Design
Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles.
Setting
General medicine community clinics.
Participants
178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days.
Interventions
Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles.
Main Outcome Measures
Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms).
Results
Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment.
Conclusions
Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.
PMID 11159568 11159568 DOI 10.1136/bmj.322.7279.134 10.1136/bmj.322.7279.134 Schellenberg et al. 2001, Schellenberg 2001
Cite this article
Schellenberg, R. (2001). Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ (Clinical research ed.), 322(7279), 134-137. https://doi.org/10.1136/bmj.322.7279.134
Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134-137. doi:10.1136/bmj.322.7279.134
Schellenberg, Ruediger. "Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study." BMJ (Clinical research ed.), vol. 322, no. 7279, 2001, pp. 134-137.
Schmidt K et al., 2018·Clin Nutr ESPEN·
Open Access
BACKGROUND & Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS(®)). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. CLINICAL The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
Premenstrual syndrome in NaProTECHNOLOGY is defined by a recurrent cluster of symptoms -- including irritability, breast tenderness, bloating, depression, and carbohydrate craving -- beginning at least four days before menses, and is associated with late-luteal deficiencies in progesterone, estrogen, and beta-endorphin identified through CrMS-anchored hormone profiling. Treatment with cycle-synchronized bioidentical progesterone, targeted HCG injections to stimulate endogenous corpus luteum function, and low-dose naltrexone to modulate opioid dynamics produces superior symptom resolution compared to SSRI therapy in Hilgers' comparative data, without suppressing ovulation.
Women diagnosed as suffering from premenstrual syndrome and symptom free controls were compared on hormonal parameters, glucose tolerance, mineralocorticoids, cholesterols, triglycerides, apolipoprotein (a), magnesium and calcium in the follicular and luteal phases of the menstrual cycle. The effect of treatment with essential fatty acids on the biochemical variables was also evaluated in a randomized, double-blind crossover design. The results showed that the hormonal and biochemical profiles of women with PMS and symptom free controls were markedly similar, except for aldosterone which was lower in the follicular and luteal phases and cholesterol which was higher in the follicular phase in women with PMS. No effects of treatment with essential fatty acids were found for any of the biochemical variables studied.
Exercise is commonly listed as a remedy for the premenstrual syndrome (PMS), although no study has proven that it is an effective therapy. Numerous reports have suggested that exercise is associated with improved mood and symptoms. In those reports, however, the diagnosis of PMS was not clearly documented, nor was the exercise carefully controlled. Preliminary evidence suggests that exercise training in ovulatory, sedentary women and intensified training in women athletes decrease mild premenstrual symptoms. Although conditioning exercise is associated with short luteal phase and anovulatory cycles, decreases in mild premenstrual symptoms occur prior to menstrual cycle changes. Controlled studies of PMS and exercise training may not only document an effective, nonpharmacologic therapy for PMS but also clarify the hormonal etiology of this complex biobehavioral phenomenon.