Case Series: Real-Life Experience with Vitex Agnus-Castus Extract Ze 440 Medication in Adolescents

Six female patients aged 12–17 years were treated for menstrual disorders, dysmenorrhea, and/or premenstrual complaints. All patients except one were at least 2 years post-menarche. One patient had an isolated menstrual cycle irregularity, while 1 patient reported a regular cycle but experienced dysmenorrhea, including associated symptoms. All remaining patients reported at least two concurrent menstrual disorders. There were no cases of acute severe bleeding or a desire for contraception. Symptoms ranged from mild abdominal pain to severe presentations with accompanying symptoms such as diarrhea, vomiting, and dizziness, which in some cases led to school absences. In suspected cases of hypermenorrhea, bleeding severity was documented using sanitary product usage (pads/tampons), and laboratory markers (hemoglobin, CRP, ferritin) were assessed. This case report has been conducted according to the CARE guidelines (online suppl. File; for all online suppl. material, see https://doi.org/10.1159/000553039 ). All patients received 20 mg of V. agnus-castus extract Ze 440 (Premens ® , Max Zeller Söhne AG, Switzerland). The VAC extract (Ze 440) is obtained from the ripe, dried, and finely ground fruits of V. agnus-castus L. using 60% ethanol (m/m) as the extraction solvent with a drug-to-extract ratio 6–12:1. Each tablet contains 20 mg of the native extract, corresponding to an average drug amount of 180 mg per tablet. Additional medications were adapted individually based on symptom presentation. Magnesium has been used to alleviate menstrual cramps associated with dysmenorrhea, and NSAIDs were administered for acute pain relief. Two patients with marked hypermenorrhea received additional tranexamic acid, and in one of these cases, supplementary treatment with norethisterone (cycle days 16–25) was initiated after 6 months to adequately reduce blood loss. One patient received Ze 440 as monotherapy. At the initial consultation, all patients were given a menstrual calendar to record the days and intensity of bleeding as well as the type and severity of associated symptoms. An app was also recommended for documenting bleeding intensity, although none of the patients used it consistently. After 3 months, follow-up included a gynecologic examination consisting of an abdominal ultrasound with a full bladder to detect uterine anomalies or early signs of adenomyosis. In 1 patient with an isolated menstrual disorder (amenorrhea), the ultrasound was omitted due to a favorable therapeutic response after 3 months. In 1 patient, sonographic findings were suggestive of adenomyosis.

During the 3-month follow-up visit, most patients reported a significant improvement in dysmenorrhea ( Table 1 ). In many cases, combining Ze 440 with magnesium allowed for a noticeable reduction or complete discontinuation of NSAID use. Menstrual cycle regularity also improved in most patients. Premenstrual complaints showed more variable outcomes. One patient with pronounced premenstrual dysphoric disorder (PMDD) initially experienced considerable improvement, but symptoms returned after 6 weeks. Due to the severity of her symptoms, she was switched to combined oral contraception and reported marked improvement after further 3 months. Patients with hypermenorrhea showed heterogeneous outcomes. One patient experienced mild improvement in bleeding intensity with Ze 440 monotherapy, while two others required additional tranexamic acid. One of these patients also began treatment with Norethisterone at the 6-month follow-up, resulting in stabilized hemoglobin and ferritin levels and an overall satisfactory clinical outcome. Throughout the treatment period, no adverse events were reported. Ze 440 was well tolerated by all patients, with no signs of gastrointestinal discomfort, allergic reactions, or other treatment-related complications. Menstrual disorder case summary

The findings of this case series are consistent with current literature on the management of menstrual disorders in adolescents [ 1 , 14 ]. Several authors emphasize that menstrual irregularities during adolescence are often physiological due to the immaturity of the HPO axis, particularly in the first 2 years after menarche [ 1 – 7 , 14 ]. These authors agree that the menstrual cycle should be considered a vital sign of adolescent health and emphasize the importance of early recognition and structured documentation of any irregularities, even when they appear to be benign. In this context, the approach described here – initiating treatment with VAC extract (Ze 440) based on thorough history taking and without immediate reliance on laboratory or imaging diagnostics – aligns with international recommendations for low-threshold, individualized care. Several authors advocate for noninvasive first-line approaches in adolescents to avoid premature hormonal suppression of the still-developing reproductive system [ 2 , 4 , 14 ]. In the present case series, treatment with Ze 440 was associated with improvements in dysmenorrhea and menstrual cycle regularity in several patients, suggesting that it may represent a useful nonhormonal option in this setting while supporting physiological regulation of the cycle rather than overriding it. Our real-world data showed that most patients experienced an improvement in dysmenorrhea and cycle regularity, with several being able to reduce or discontinue NSAID use entirely. This is clinically relevant given the high burden of pain-related school absenteeism in this population. Ze 440 was well tolerated, and no side effects were reported. However, several patients received concomitant therapies including magnesium, NSAIDs, tranexamic acid, or subsequent hormonal treatment as part of individualized routine clinical care. Therefore, the specific contribution of Ze 440 to symptom improvement cannot be determined with certainty, and the findings should be interpreted as exploratory real-world observations rather than evidence of causal efficacy. The variability in response to VAC among patients with severe premenstrual symptoms such as PMDD highlights the need for individualized treatment strategies. One patient in our cohort was advised to switch to combined oral contraception due to symptom recurrence and high distress levels – an intervention that should be weighed carefully in young adolescents. As highlighted by Anthon et al. [ 14 ], hormonal therapies should be reserved for cases with clear indications, particularly when contraception is not required. In one case, a change in treatment strategy was suggested after the follow-up ultrasound after 3 months revealed sonographic signs of adenomyosis uteri. Although rare in adolescents, such findings underscore the importance of considering structural anomalies when treatment response is limited. Another strength of Ze 440 is its adaptability for long-term use. According to the patient information, a treatment duration of at least 3 months is recommended (including during menstruation), as the therapeutic effect builds up over this period. In adolescents, Ze 440 may initially be administered continuously over a period of 6 months. Upon improvement of symptoms, a sequential intake regimen – limited to the week prior to and during menstruation – can be considered. In cases of unpredictable menstrual cycles accompanied by dysmenorrhea, an intermittent regimen may be applied, consisting of 3 months of continuous intake followed by a 3-month treatment-free interval. The clinical observations from the current adolescent cases are also in line with findings from adult populations. A systematic review by Cerqueira et al. [ 15 ] analyzed eight randomized controlled trials of VAC for PMS and PMDD and found consistent evidence of clinical benefit over placebo and active comparators. VAC was generally well tolerated, with only mild side effects. Similarly, a meta-analysis by Csupor et al. [ 16 ] of three placebo-controlled randomized clinical trials confirmed that standardized VAC extracts, particularly Ze 440, significantly improved PMS symptoms, with women being 2.6 times more likely to respond compared to placebo. The results presented here in adolescents are also in line with a recent large-scale real-world study in adult women conducted by Höller et al. [ 17 ], which evaluated the effectiveness of VAC products in over 1,700 patients with menstrual cycle disorders. The study demonstrated significant improvements in dysmenorrhea, cycle regularity, and premenstrual breast tenderness after 3 months of treatment with VAC, as well as marked improvements in quality of life. Interestingly, although the number of adolescent cases in this observation is relatively small, the direction and magnitude of effect are similar to those observed in the adult cohort, suggesting a comparable therapeutic potential of VAC across age-groups. This supports the early, structured use of phytotherapeutics like Ze 440, especially in patients for whom hormonal therapy may not be indicated or desired. Several limitations of this case series should be acknowledged. First, the small sample size and observational design limit the generalizability of the findings. Second, symptom assessment was primarily based on patient-reported outcomes, menstrual calendars, medication use, and selected laboratory parameters in cases of hypermenorrhea, while validated scoring systems for pain intensity, menstrual bleeding, or quality of life were not consistently applied. Future prospective studies should incorporate standardized assessment tools to allow more objective evaluation of treatment effects. Third, spontaneous improvement related to ongoing maturation of the hypothalamic-pituitary-ovarian axis cannot be excluded, particularly in adolescents with irregular cycles or amenorrhea. Although most patients were more than 2 years post-menarche and had clinically relevant symptoms requiring medical attention, the present observational design does not allow differentiation between treatment effects and the natural course of adolescent cycle maturation. Lastly, the avoidance of overtreatment is a recurring theme in adolescent gynecology. Combined hormonal contraceptives are still frequently prescribed to manage menstrual symptoms yet often represent overtreatment in patients who do not need contraception. In this context, nonhormonal approaches such as Ze 440 may offer symptom relief while avoiding interference with the natural development of the HPO axis.

Menstrual disorders are among the most frequent gynecological concerns in adolescence, a developmental period characterized by dynamic hormonal, physical, and psychosocial changes [ 1 , 2 ]. These disturbances – including irregular bleeding, dysmenorrhea, and premenstrual symptoms – can have a significant impact on adolescents’ quality of life, emotional well-being, and academic performance [ 3 , 4 ]. While irregular menses are common during the first 1–2 years following menarche due to immaturity of the hypothalamic-pituitary-ovarian (HPO) axis, persistent deviations from a typical cycle length (25–35 days) should prompt further evaluation to exclude underlying endocrine, hematologic, or structural causes [ 5 , 6 ]. Leading pediatric and adolescent gynecology guidelines emphasize the menstrual cycle as a vital sign in adolescent health care and recommend consistent documentation and early assessment of abnormal patterns [ 5 – 7 ]. Despite this awareness, treatment options for cycle-related symptoms in adolescents remain limited. Combined oral contraceptives are frequently prescribed, but their use may be inappropriate for adolescents who do not require contraception or who are reluctant to initiate hormonal therapy due to personal, developmental, or medical considerations [ 2 , 4 ]. This therapeutic gap underscores the need for well-tolerated, effective non-hormonal options. Vitex agnus-castus (VAC), also known as chaste tree, has been used traditionally for the treatment of menstrual disturbances and has demonstrated clinical efficacy in adults with cycle irregularities, dysmenorrhea, and premenstrual syndrome (PMS) [ 8 ]. Its dopaminergic mechanism leads to suppression of prolactin and indirect modulation of gonadotropin release, contributing to the stabilization of menstrual cycles [ 9 – 11 ]. VAC extracts, such as Ze 440 (Premens ® ), have been shown to improve both physical and emotional menstrual symptoms in randomized controlled trials and observational studies [ 9 , 11 – 13 ]. A dose-finding study identified 20 mg per day as the optimal dose for improving PMS symptoms [ 13 ]. Despite the broad clinical use of VAC in adult women, there is a lack of published evidence for its use in adolescents – a population with distinct physiological and psychosocial characteristics. This case series aims to provide real-world data on the use of Ze 440 in adolescents with various menstrual disorders, thereby contributing to the limited evidence base for phytotherapeutic interventions in adolescent gynecology.

The author has no conflict of interest to declare.

This study was not supported by any sponsor or funder.

The Ethics Committee of Eastern Switzerland (Ethikkommission Ostschweiz, EKOS) confirmed that this project is not subject to ethical approval requirements. Written informed consent was obtained from the patients (or their parent/legal guardian/next of kin) for publication of this case report.

K.E.: conceptualization, investigation, and writing.