Curcumin, a bioactive supplement for premenstrual syndrome and dysmenorrhea: A systematic review of randomised clinical trials

Abstract

Introduction

The anti-inflammatory nature of curcumin suggests its potential to modulate the body's inflammatory processes, offering a novel avenue for mitigating heightened inflammatory responses often observed in conditions like PMS and dysmenorrhea.

Methods

MEDLINE, Cochrane Central, ScienceDirect, Web of Science, CINAHL, ClinicalTrials.gov, and Google Scholar from their inception to November 12, 2023. The review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes of interest encompassed evaluating the severity of PMS symptoms and dysmenorrhea, including physical symptoms, behavioral symptoms, mood symptoms. Additionally, the study focused on assessing inflammatory biomarkers, Iron profile and Vitamin D status as other outcomes.

Results

Ten randomized controlled trials have evaluated the effectiveness of curcumin in reducing premenstrual syndrome and dysmenorrhea symptoms in women. These studies used various scales such as the Premenstrual Syndrome Screening Tool (PSST) and visual analog scale. Out of ten trials, six of them reported a significant decrease in PMS and dysmenorrhea symptoms. Additionally, six studies evaluated curcumin's association with inflammatory markers, hematological parameters, iron profile, Vitamin D, and sleep patterns. This demonstrated significant association between curcumin and inflammatory markers (nitric oxide metabolites, BDNF, IgE, Il-10, IL-12, hs-CRP), and vitamin D status.

Conclusion

The findings of this systematic review suggest that curcumin holds promise in the management of PMS and dysmenorrhea. However, further research is needed to establish optimal dosages and treatment durations, considering potential interactions with iron metabolism. The results encourage the exploration of curcumin as a complementary approach in enhancing the overall well-being of individuals affected by these menstrual conditions.

Highlights

• •Curcumin, a turmeric extract, shows promise in reducing premenstrual syndrome (PMS) and dysmenorrhea symptoms through its anti-inflammatory, immunomodulatory, and antioxidant properties.
• •Out of ten randomized clinical trials, six reported significant symptom improvement, with notable effects on mood, behavior, and physical symptoms.
• •Curcumin positively influences inflammatory biomarkers and vitamin D status but has minimal effects on iron profiles.
• •While curcumin demonstrates therapeutic potential, further research is needed to determine optimal dosage and duration.
• •This review highlights curcumin as a safe, complementary approach for managing menstrual disorders.

Introduction

Dysmenorrhea is a condition marked by recurrent pain in the lower abdomen or pelvis during the menstrual period. It affects a substantial percentage of females, with prevalence varying from 45 % to 95 % [1]. On the other hand, Premenstrual Syndrome (PMS) is characterized by emotional symptoms such as irritability, anxiety, depression, and physical symptoms like abdominal bloating and breast tenderness occurring around or before the commencement of menstruation [2]. These menstrual disorders significantly impact women's well-being and pose concerning challenges for healthcare providers.

The use of conventional treatments is not without drawbacks and inherent risks. Nonsteroidal anti-inflammatory drugs (NSAIDs), known for their effectiveness in pain relief, carry the risk of causing gastrointestinal issues. Additionally, they pose potential threats to the kidneys, liver, and circulatory system, thereby increasing the likelihood of thromboembolic problems [3], [4]. Hormonal therapies may result in side effects such as nausea, breakthrough bleeding, breast tenderness, and, in severe cases, an elevated risk of blood clotting, specifically deep vein thrombosis [3]. Antidepressants, particularly SSRIs, come with side effects like nausea, sleep problems, and decreased libido, limiting their tolerability for some individuals [3]. These drawbacks underscore the need for alternative, safer, and more personalized approaches in the management of menstrual disorders.

The limitations of conventional treatments have sparked growing interest in alternative, traditional approaches [5]. Among these, curcumin—a polyphenolic pigment extracted from the turmeric plant (Curcuma longa)—has emerged as a promising candidate for managing dysmenorrhea and PMS. [5]. Curcumin is distinguished by its proactive therapeutic approach, effectively managing symptoms while minimizing the drawbacks associated with conventional interventions. Interest in curcumin stems from well-documented properties, including anti-inflammatory, immunomodulatory, and antioxidant effects [6], [7].

The anti-inflammatory nature of curcumin suggests its potential to modulate the body's inflammatory processes, offering a novel avenue for mitigating heightened inflammatory responses often observed in conditions like dysmenorrhea [8]. Its immunomodulatory effects indicate a capacity to influence the immune system, presenting a possible mechanism for managing immune-related aspects of both dysmenorrhea and PMS [9]. Additionally, the antioxidant properties of curcumin suggest a protective effect against oxidative stress, implicated in various health conditions affecting women's reproductive health [10]. These diverse properties make curcumin an attractive option for addressing the complex inflammatory responses associated with dysmenorrhea and potentially alleviating the severity of PMS symptoms.

This systematic review aims to enhance our understanding of curcumin's therapeutic potential in dysmenorrhea and PMS by analyzing randomized clinical trials. Providing a comprehensive and evidence-based analysis, it addresses the limitations of conventional treatments, laying the foundation for informed clinical decision-making in women's health. The findings are expected to guide future research, shaping more tailored approaches and contributing valuable insights to the global medical community for the benefit of women worldwide.

Unlike previous systematic reviews that primarily focused on symptom relief outcomes, the present review incorporates newly published randomized controlled trials (up to November 2023) and expands the analytical scope to include inflammatory biomarkers, iron profile, vitamin D status, and sleep parameters. This broader perspective provides novel insights into the physiological mechanisms through which curcumin may influence menstrual health.

Methods

This review strictly followed the PRISMA 2020 guidelines. A concise summary of our search terms includes: (“curcumin” OR “turmeric”) AND (“premenstrual syndrome” OR “PMS” OR “dysmenorrhea”). The PRISMA flowchart (Fig. 1) and checklist (Table S2) outline the screening and inclusion process in full detail. [11] and was conducted in alignment with the framework outlined by the Cochrane collaboration [12]. The study has been registered on PROSPERO (CRD42023482358).

Fig. 1.

PRISMA flowchart of the literature search.

Data sources and search strategy

We performed an extensive review of the literature, searching databases such as MEDLINE, Cochrane Central, ScienceDirect, Web of science, CINAHL, ClinicalTrials.gov, and Google Scholar from their inception to November 2023. No limitations were set regarding time, language, or sample size. Comprehensive search strategies for each database are delineated in Supplementary Table S1. Furthermore, we examined the bibliographies of pertinent review articles and explored gray literature sources, including ClinicalTrials.gov and preprint sites like Medrxiv. This method was employed to ensure a comprehensive and diverse coverage of relevant studies, aiming for a thorough exploration of the available literature.

Study selection and eligibility criteria

The systematic search resulted in articles that were then imported into EndNote Reference Manager (Version X7.5; Clarivate Analytics, Philadelphia, Pennsylvania). Within EndNote, we systematically screened for and removed any duplicate entries.

Two reviewers (MHS and STR) independently assessed the remaining articles initially by examining their titles and abstracts. Subsequently, they conducted a thorough review of the full texts to validate their relevance. Any discrepancies were resolved through group discussion. Studies were chosen if they satisfied the following predetermined eligibility criteria a) randomized controlled trials (RCTs) with the intervention group receiving either curcumin alone or curcumin in combination with piperine; b) Female patients of reproductive age (≥ 18 years) with PMS or Primary dysmenorrhea. Duplicate records, case reports, commentaries, and editorials were excluded. Animal studies were also excluded from this paper.

Due to marked heterogeneity among studies in terms of intervention duration, dosage forms, comparators, and outcome measures (e.g., PSST, VAS, SPID), quantitative synthesis (meta-analysis) was not feasible

Data extraction, quality assessment, and risk of bias

Data extraction for the study on the severity of premenstrual syndrome (PMS) symptoms and inflammatory biomarkers involved recording baseline characteristics, study type, study year, sample size, age, and gender onto a standardized Microsoft Excel sheet. The primary outcomes of interest encompassed evaluating the severity of PMS symptoms and dysmenorrhea, including physical symptoms, behavioral symptoms, mood symptoms. Additionally, the study focused on assessing inflammatory biomarkers (C-reactive protein, Neutrophil to Lymphocyte ratio, Platelet to Lymphocyte ratio, Serum Immunoglobulin-E (IgE), Interleukin-10 (IL-10) levels, Interleukin-12 (IL-12) levels serum brain derived neurotrophic factor, nitric oxide, red cell distribution width, mean platelet volume and red blood cell distribution width ratio), Iron profile and Vitamin D status as other outcomes. Methodological quality assessment was conducted by two reviewers (MHS and STR) using the Cochrane risk of bias assessment tool for rigorous evaluation [13].

Results

Study selection

An initial literature search on seven electronic databases retrieved 6720 articles, out of which 950 duplicate articles were removed and 5640 articles were excluded based on the screening of titles and abstracts. Further, 130 full-text articles were reviewed, out of which 120 articles were excluded as they did not meet the inclusion criteria. Hence, 10 randomized control trials were selected for this systematic review. A summarized literature search is provided in the PRISMA flowchart (Fig. 1). The Table 1 summarizes the characteristics of included studies and population.

Table 1.

Study and population characteristics.

Author (year of study)	Study design	Total population (N)	Age (Mean age± SD)	Intervention (n), Control (n)	Duration	Tools of assessment	Outcomes
Fanaei et al. (2015)	RCT	63 women with PMS	24.55 ± 7.65	100 mg curcumin/12 hr (32); Placebo (31)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	PSST scale	Severity of PMS symptoms; significantly decreased (p ˂ 0.001) Behavioral symptoms; (p ˂ 0.001) Mood symptoms; significantly decreased (p < 0.001). Physical symptoms; significantly decreased (p ˂ 0.001) Serum BDNF levels; significantly increased (p ˂ 0.001)
Hesami et al. (2020)	RCT	121 women with primary dysmenorrhea*	22.66 ± 2.09	500 mg of powdered turmeric (30); Placebo (31)	5 days (2 days before and 3 days after the start of menstruation) for 1 menstrual cycle	Visual Analog Scale	Pain intensity; significantly decreased (p = 0.043)
Tabari et al. (2020)	RCT	74 women with dysmenorrhea	26.5 ± 4.91	500 mg of turmeric extract based on 5.47 mg curcumin/ 2 capsules daily (37); Placebo (37)	first 3 days of menstruation for 2 successive menstrual cycle	Pain severity: Visual Analog Scale	pain severity 3 h post consumption; no significant decrease in curcumin group (p > 0.05). pain duration in 1st cycle; no significant decrease in curcumin group(p > 0.5). pain duration in 2nd cycle; no significant decrease in curucmin group(p > 0.05)
Bahrami et al. (2021)	RCT	118 women with both PMS and dysmenorrhea	20.85 ± 1.64	500 mg curcuminoids + 5 mg piperine/ daily (57); Placebo (61)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	PMS symptoms: PSST scale Dysmenorrhea severity: Visual Analog Scale	PMS symptoms; significantly decreased (p < 0.001) Mean bleeding time; no significant decrease (p > 0.05), duration of bleeding; no significant decrease (p > 0.05) Dysmenorrhea severity; significantly decreased (p < 0.001)
Bahrami et al. (2022)	RCT	77 women with both PMS and dysmenorrhea	21.09 ± 1.67	500 mg curcumin+ 5 mg piperine/ daily (38); Placebo (39)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	ELISA kits	Inflammatory markers: mean serum IgE levels; significantly decreased (p = 0.001); mean serum IL−10 levels; no significant difference(p = 0.75); mean serum IL−12 levels; no significant difference (p = 0.40)
Arabnezhad et al. (2022)	RCT	73 women with both PMS and dysmenorrhea	21 ± 1.744	500 mg of curcuminoid+ 5 mg piperine/daily (36); Placebo (37)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	ELISA kits	Vit-D levels; significantly increased (p = 0.045) 2)Vit-D status, significantly improved (p = 0.039)
Talebpour (2023)	RCT	73 women with both PMS and dysmenorrhea	21.05 ± 1.62	500 mg of curcuminoid+ 5 mg piperine/daily (36); Placebo (37)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	WBC, Neutrophil%, RDW,MPV,NLR,PLR,RPR, Hb: Automated commercial cell counter hsCRP, Fe levels, TIBC: Autoanalyzer kits Ferritin: ELISA kits	Inflammatory biomarkers: hsCRP; significantly decreased (p = 0.039), WBC; no significant change (p = 0.13), Neutrophil %; no significant change (p = 0.45), RDW; no significant change (p = 0.21), MPV; no significant change(p = 0.49), NLR; no significant change (p = 0.91), PLR; no significant change (p = 0.94), RPR; no significant change (p = 0.22) Iron Profile: Fe levels; no significant decrease (p = 0.37), TIBC; no significant change (p = 0.37), Ferritin;no significant change(p = 0.62), Hb; no significant change (p = 0.98)
Agarwal et al.(2023)	RCT	60 women with primary dysmenorrhea	26.54 ± 4.37	1000 mg capsule (turmeric–boswellia–sesame formulation)/ daily (30); Placebo (30)	During menstruation for 1 menstrual cycle when menstrual cramp pain was ≥ 5 in severity on the numerical rating scale (NRS) questionnaire.	SPID at 6 h post-dosing: Numerical rating scale (0−10) Total Pain Relief Score: categorical pain relief scale (0−4)	Dysmenorrhea symptoms: Least-square-mean-pain intensity difference (SPID) at 6 h post-dosing; a significant difference (p < 0.0001) Total Pain Relief score; significantly decreased (p < 0.001)
Farrokhfall et al. (2023)	RCT	73 women with both PMS and dysmenorrhea	20.80 ± 1.96	500 mg of curcuminoid plus piperine/ daily (36); Placebo (37)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	Serum NO levels: Griess assay PMS symptoms: PSST scale	Serum NO metabolites; significantly decreased in curcumin group post-intervention(p = 0.048) PMS symptoms; significantly decreased in curcumin group(p < 0.01)
Seyedabadi et al. (2023)	RCT	117 women with both PMS and dysmenorrhea	20.25 ± 0.99	500 mg curcumin plus 5 mg piperine/daily (57); Placebo(60)	10 days (7 days before and 3 days after start of menstruation) for 3 successive menstrual cycles	Insomnia: Insomnia Severity Index Daytime Sleepiness: Epworth Sleepiness Scale Difficult sleep initiating: Based on the following 2 questions (1) “Do you experience difficulty falling asleep at nights?” (2) “How often have you woken up hurried and have problem going back to sleep? Sleep duration was measured using this question: “how many hours of real nocturnal sleep do you get on weekdays? Short sleep duration: measured using this question: “how many hours of real nocturnal sleep do you get on weekdays? PMS symptoms: PSST scale	Insomnia score: no significant decreased in curcumin group (p = 0.072) Daytime sleepiness score: no significant decrease in curcumin group (p = 0.15) Nocturnal sleep (hour): significantly decrease in curcumin group (p < 0.001) Difficult sleep initiation: no significant improvement in curcumin group (p = 0.87) Short sleep duration: no significant improvement in curcumin group (p = 0.92) PSST score: significant decrease in the curcumin group (p < 0.001)

BDNF; Brain Derived Neurotrophic factor, Hscrp; High-Sensitivity-C-reactive-protein, MPV; Mean Platelet Volume, NLR; Neutrophil Lymphocyte Ratio, PLR; Platelet Lymphocyte Ratio, RDW; Red Cell Distribution Width, RPRRed Blood Cell Distribution Width: Platelet Ratio, WBC; White Blood Cell

* total population does not equals the sum of intervention and placebo group because of multiple out of interest interventional groups

Risk of bias of included studies

The Cochrane Risk of Bias Assessment tool (RoB 2.0, version 2019) [14] was conducted to evaluate the overall risk of bias in the included studies. The tool comprises five domains that were used to assess the biases of the trials. If some trials had a high risk of bias in any domain, they were considered to have a high risk of bias overall whereas if a trial had a low risk of bias or some concern in any domain were considered to have low risk or some concerns overall. All the studies were analyzed on the intention to treat model. All the studies [14], [15], [16], [17], [18], [19], [20], [21] showed some concern overall and it was due to the risk of some concern in the deviations from the intended intervention domain (D2) in nine studies [15], [16], [17], [18], [19], [20], [21], [22] whereas risk of some concern was found to be in the measurement of the outcome in one study [22]. The supplementary file summarizes the Quality assessment in Fig. 2, Fig. 3.

Fig. 2.

Risk of bias summary of the included studies.

Fig. 3.

Risk of bias graph of the included studies.

Synthesis of results

Effects of curcumin on PMS symptoms

There were four studies [14], [16], [21], [22] which evaluated the efficacy of curcumin in the improvement of premenstrual symptoms. Fanaei et al. [14] showed a significant change in the total severity of PMS (p < 0.001) along with a significant change in the behavioral, mood, and physical symptoms after three months of intervention (p = 0.005, p < 0.001, p < 0.001), respectively. Bahrami et al. [16] reported a significant effect on PMS symptoms (p < 0.001) whereas it did not affect the mean bleeding time (p > 0.05), and duration of bleeding (p > 0.05) for both the interventional and control group. It demonstrated a relative improvement of 56.1 % in the alleviation of PMS in the interventional group vs. 36.1 % in the control group. A study conducted by Farrokhfall et al. [21] also showed a significant decrease in PMS symptoms in the curcumin group (p < 0.01). Seyedabadi et al. [22] evaluated the PSST score and found out that there was a significant decrease in the PSST score of patients treated with curcumin for premenstrual syndrome (p < 0.001).

Effects of curcumin on inflammatory markers

Four studies [14], [17], [19], [21] evaluated the association between the effect of curcumin on different inflammatory markers such as CRP, NLR, PLR, serum IgE levels, serum IL-10, IL-12 levels, serum BDNF levels, NO metabolites, neutrophils percentage, red cell distribution width (RDW), mean platelet volume (MPV), and red blood cell distribution width: platelet ratio (RPR). Fanaei et al. [14] reported that three months of intervention with curcumin led to significantly increased serum levels of BDNF as compared to the control group (p < 0.001) which concurrently reduced the severity of PMS. According to a study by Bahrami et al. [17], there was a significant reduction in mean serum IgE levels (p = 0.001) in the treatment group, but not in the placebo group (p = 0.12). However, there was no significant difference in serum concentrations of IL-10 and IL-12 between the two groups (p > 0.05). Talebpour et. al [19] showed a significant decrease in the high-sensitivity CRP levels in the interventional group (p = 0.039] in comparison to the placebo group (p = 0.38) whereas hematological inflammatory markers such as WBC count, neutrophil percentage, RDW, MPV, NLR, PLR, and RPR didn’t show significant results (p > 0.05). Nitric oxide metabolites reduce pain sensitivity by acting as a neuromodulator, and it is involved in the pathophysiology of primary dysmenorrhea and PMS. Farrokhfall K. et al. [21] found that the curcumin group showed a significant decrease in the levels of serum NO metabolites after the intervention (p = 0.048).

Effects of curcumin on the severity of dysmenorrhea

Three studies [15], [16], [20] assessed the effect of curcumin on the severity of dysmenorrhea and showed that pain intensity was significantly reduced in the patients who were treated with curcumin (p = 0.043) [15]. Agarwal D et al. [20] assessed the least-square-mean-pain intensity difference (SPID) at 6-h post-dosing and total Pain Relief score, and it showed a significant decrease as compared to the control group (p < 0.0001) and (p < 0.001), respectively.

Effects of curcumin on iron profile

Single study [19] assessed the effect of curcumin on the iron profile including hemoglobin, iron, total iron binding capacity, and ferritin and it showed an insignificant difference between the interventional and control groups at the end of the intervention (p > 0.05).

Effects of curcumin on Vitamin D status

One study [18] reported the effects of curcumin on the levels and status of vitamin D in patients with PMS and dysmenorrhea. It demonstrated a significant increase in the levels of vitamin D (p = 0.045) and significantly improved the status of vitamin D in the patients after undergoing intervention (p = 0.039).

Effect of curcumin on sleep pattern

One study [22] evaluated the effect of curcumin on the disturbance of sleep pattern. It showed that there was a significant decrease in the nocturnal sleep (hour) in interventional group (p < 0.001) whereas there was no significant effect of curcumin on insomnia score (p = 0.072), daytime sleepiness score (p = 0.15), difficulty in initiation of sleep (p = 0.87), and short sleep duration (p = 0.92), respectively.

Discussion

While most included studies demonstrated an overall low-to-moderate risk of bias, concerns in the ‘deviations from intended intervention’ and ‘measurement of outcome’ domains warrant caution. These limitations may introduce performance or detection bias, reducing confidence in the generalizability of the findings. Hence, although the direction of evidence supports curcumin’s beneficial effects, the certainty of evidence remains moderate

In this systematic review of the literature, we observed that collectively curcumin supplementation positively impacts the behavioral, mood, physical symptoms, and total severity of PMS, but did not affect the bleeding time. Our findings also showed that curcumin supplementation have a beneficial effect in the treatment of inflammatory response and oxidative stress by influencing the levels of high-sensitivity CRP, BDNF, serum IgE, serum NO metabolites and vitamin D. However, no such impact was observed with respect to serum concentrations of IL-10 and IL-12, hematological inflammatory markers such as WBC count, neutrophil percentage, RDW, MPV, NLR, PLR, and RPR.

Curcumin, also known as diferuloylmethane, is the primary curcuminoid found in turmeric and is recognized for its various therapeutic properties [23], [24]. It has been employed in the treatment of diverse conditions, with a growing body of evidence suggesting its potential benefits in areas such as depression, inflammation, oxidation, microbial infections, and blood sugar regulation. Additionally, curcumin has demonstrated protective effects in various animal models of neuropsychiatric disorders [25], [26]. While the precise mechanism of its neuroprotective action remains unclear, studies suggest that curcumin may influence the release of certain neurotransmitters [27]. Notably, in women experiencing premenstrual syndrome (PMS), there are observed differences in the plasma levels of specific neurotransmitters during the late luteal phase [28]. Given the promising therapeutic outcomes of previous research, there is potential for curcumin to be utilized as a cost-effective and efficient herbal medicine.

Menarche represents a significant developmental milestone in young girls and serves as a crucial indicator of female reproductive health [29]. A substantial proportion, ranging from 40 % to 99 %, of women in their reproductive years’ experience menstrual complications, including primary dysmenorrhea (PD), irregular menstrual cycles, abnormal uterine bleeding, and premenstrual syndrome (PMS) [30]. The occurrence of menstrual issues is believed to be linked to hormonal fluctuations, genetic predisposition, stress, dietary factors, and lack of physical activity [31], [32]. Among these complications, PD and PMS are the most commonly reported gynecological issues in young women, exerting a negative impact on various aspects of women's quality of life [33].

Premenstrual syndrome (PMS) manifests as a cyclic pattern of mood and somatic complaints during the luteal phase of the menstrual cycle [34]. It encompasses a spectrum of over 150 emotional, behavioral, and physical signs and symptoms, including but not limited to backache, nausea, fatigue, depression, mood swings, anxiety, and breast tenderness [30]. On the other hand, primary dysmenorrhea (PD) is characterized by recurring, painful cramps in the midline of the lower abdomen. Importantly, these cramps occur without any pelvic pathology and typically manifest just before or immediately after menstruation [35].

Changes in the concentrations of prostaglandins (PGs) and neurotransmitters are believed to play a potential role in the development of premenstrual syndrome (PMS). PGs are primarily associated with the occurrence of physical symptoms, while neurotransmitters are implicated in the emergence of psychological manifestations of PMS [36], [37]. In line with this, one contributing factor to primary dysmenorrhea (PD) is an increase in the production of uterine PGs, stemming from the activity of cyclooxygenase (COX)-2 and the release of arachidonic acid [38].

During menstruation, there is a decrease in progesterone and estradiol levels, accompanied by an increase in the expression of endometrial collagenases and matrix metalloproteinases (MMPs). This leads to an inflammatory response and the breakdown of the endometrium [39]. Additionally, there is a release of phospholipids, followed by the production of prostaglandins (PGs) by interleukins (IL), lytic enzymes, prostacyclins, and thromboxane A2 through the action of COX-1 and −2 [39], [40]. PGs affect nociceptors, resulting in uterine smooth-muscle contractions, spasmodic pain, and the expulsion of the endometrium [40]. In women with primary dysmenorrhea (PD), concentrations of PGE2 and PGF2-α are higher compared to healthy women [39].

Curcumin has been documented for its effectiveness in treating various inflammatory conditions, exerting its impact on pro-inflammatory cytokines and inhibiting the generation of nitric oxide (NO) [27], [41]. Both in vitro and in vivo studies have underscored the positive influence of curcumin on endometriosis [42], [43]. This is evident in its inhibition of oxytocin-stimulated uterine contractions, suggesting an antispasmodic effect [44]. Moreover, curcumin supplements have been demonstrated to reduce the production of prostaglandin E2 (PGE2) [45]. In the context of premenstrual syndrome (PMS), curcumin in women has shown the potential to regulate neurotransmitters and biomolecules, exhibit antioxidant and anti-nociceptive effects, and reduce oxidative stress (OS) [27].

among involved studies in this review, three studies evaluating the efficacy of curcumin on premenstrual symptoms [15], [17], [22], Fanaei et al. found a significant improvement in the total severity of PMS and changes in behavioral, mood, and physical symptoms after three months of intervention [15]. Bahrami et al. reported a significant effect on PMS symptoms with a relative improvement of 56.1 % in the interventional group compared to 36.1 % in the control group [17]. Farrokhfall et al. also observed a significant decrease in PMS symptoms in the curcumin group [22]. Overall, these studies suggest a positive impact of curcumin in alleviating premenstrual symptoms.

Curcumin influences the inflammatory response by reducing the expression of inflammatory biomolecules and inhibiting the release of proinflammatory cytokines, as noted in studies by Bahrami et al. [46], [47]. There is substantial evidence suggesting the potential therapeutic effects of curcumin on dysmenorrhea pain and the severity of premenstrual syndrome (PMS) from studies by Fanaei et al. [48], Khayat et al. [49], Kheirkhah [50], and Rahman et al. [51].

Furthermore, curcumin has been found to be safe, with no serious adverse events reported even at high doses (8–12 g daily for 3 months), according to Karandish et al. [52]. However, it is important to note that curcumin may have iron-binding capacity, act as an iron chelator, and induce features of iron metabolism, potentially leading to iron deficiency anemia, particularly in individuals with suboptimal iron concentrations, as suggested by Chin et al. [53], Jiao et al. [54], and Shehzad et al. [55]. One study [14] reported a significant increase in serum BDNF levels after three months of curcumin intervention, which correlated with a reduction in the severity of PMS. According to Bahrami et al. [17], the treatment group showed a significant reduction in mean serum IgE levels, but there was no significant difference in serum concentrations of IL-10 and IL-12 compared to the placebo group. Talebpour A. et al. [19] observed a significant decrease in high-sensitivity CRP levels in the curcumin intervention group compared to the placebo group. However, hematological inflammatory markers did not show significant differences. Farrokhfall K. et al. [21] found a significant decrease in the levels of serum NO metabolites in the curcumin group after the intervention. In the context of curcumin impact on iron profile, there is no significant effect of curcumin in this field [19].

The potential involvement of vitamins and mineral status in the development of common features in premenstrual syndrome (PMS) and dysmenorrhea has been reported, suggesting a potential mechanism for preventing and/or treating systemic menstrual problems [30], [56], [57]. There is evidence indicating an inverse relationship between vitamin D (Vit D) status and the risk of depressive symptoms [58], [59], fibromyalgia [60], and uterine leiomyomas [61]. Additionally, low levels of Vit D and calcium may contribute to dysmenorrhea pain by either increasing prostaglandin genesis or reducing intestinal calcium absorption [62]. Furthermore, a higher intake of vitamin D may reduce the risk of PMS by influencing the activities of sex steroid hormones and neurotransmitters [63]. One of the included studies in this review demonstrated a significant increase in the levels of vitamin D and significantly improved the status of vitamin D in the patients after undergoing intervention [64].

Hesami et al. [15] illustrated that the administration of turmeric supplement in a fixed dose of 500 mg in five days (pre and during the menstruation), might be more helpful in abating the menstrual pain even more than regular mefenamic acid (250 mg). Furthermore, combination of these two could be far more effective. Additionally, total pain relief and pain intensity difference evaluated by a pain relief score and a numerical rating scale showed that turmeric–boswellia–sesame formulation was significantly better than placebo [4].

Complications during menstruation can have notable negative impacts on emotional well-being, thereby disrupting overall quality of life. Increasing evidence suggests a link between the quality of sleep and menstrual patterns, specifically the influence of symptoms associated with menstruation on sleep health [35], [65], [66], [67]. Recently, research has indicated that the severity of premenstrual syndrome (PMS) is associated with poor sleep quality, shorter sleep duration, and insomnia [68]. Previous findings have also shown that women with premenstrual dysphoric disorder (PD) exhibit higher scores for insomnia, daytime dizziness, and sleep apnea compared to those without PD [69].

On the other hand, disrupted sleep patterns not only adversely affect cognitive abilities, emotional functioning, and various daytime processes but also have a profound impact on hormonal regulation [70]. Neuroendocrine disruptions caused by mental distress, particularly sleep deprivation, can significantly influence the functioning of the hypothalamic-pituitary-adrenal axis, consequently affecting the menstrual cycle [71], [72].

While curcumin has been extensively studied in various clinical contexts, there is a limited number of clinical trials investigating its impact on sleep-related issues, and the findings have been inconsistent [73], [74]. The majority of studies have focused on the effects of curcumin on sleep in experimental animals. In rats, curcumin has demonstrated the ability to prevent neuronal loss, memory impairment, as well as structural and behavioral changes induced by chronic sleep deprivation by reducing oxidative stress [75], [76], [77]. At the level of sleep pattern, Our review included one study [78] that showed a significant effect of curcumin administration by decreasing the nocturnal sleep (hour). However, the study demonstrated that no significant effect of curcumin on insomnia score, daytime sleepiness score, difficulty in initiation of sleep, and short sleep duration [78].

Although several trials reported statistically significant reductions in symptom scores, the clinical magnitude of improvement was modest in most cases. The observed reductions may not always translate to substantial relief in real-world settings, particularly given small sample sizes and short follow-up durations. Therefore, larger, well-powered RCTs are required to confirm clinically meaningful benefits. Additionally, The heterogeneity across study designs and outcome measures limited the ability to pool data statistically. This variation likely reflects differences in trial protocols and patient characteristics, underscoring the need for standardized outcome measures in future research.

Conclusion

In conclusion, the systematic review of studies examining the efficacy of curcumin in the treatment of premenstrual syndrome (PMS) and dysmenorrhea reveals promising results. The analyzed studies consistently demonstrate a positive impact of curcumin on various aspects of menstrual health, including the alleviation of PMS symptoms and dysmenorrhea pain. Notably, curcumin's anti-inflammatory properties and its modulation of inflammatory markers, along with its influence on neurotransmitters and hormonal activities, contribute to its potential therapeutic effects. The reviewed literature suggests that curcumin may serve as a safe and effective complementary approach in managing menstrual discomfort.

Abbreviations

PMS: Premenstrual Syndrome

PD: primary dysmenorrhea

NSAIDs: Nonsteroidal Anti-Inflammatory Drugs

SSRIs: Selective serotonin reuptake inhibitor

CRP: C-reactive protein

NLR: neutrophil to lymphocyte ratio

BDNF: brain-derived neurotrophic factor

NO: nitric oxide

RDW: red cell distribution width

MPV: mean platelet volume

RPR: red blood cell distribution width: platelet ratio

TIBC: total iron binding capacity

PSST: Premenstrual syndrome screening tool

SPID: Square Pain Intensity Difference

RoB: Risk of Bias Assessment tool

COX: cyclooxygenase

CRediT authorship contribution statement

Kanwal Ashok Kumar: Writing – original draft. Sondos Abdelrhman: Writing – review & editing. Syeda Tayyaba Rehan: Supervision. Nor Azlia Abdul Wahab: Supervision, Validation. Mashhour Naasan: Supervision. Oadi N. Shrateh: Writing – review & editing, Writing – original draft, Visualization, Validation, Project administration, Methodology, Data curation. Muhammad Hamza Shuja: Methodology. Areesha Jawed: Writing – original draft.

Funding

No funding was received for the redaction of the systematic review.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary material

Table S1

Supplementary material

Table S2

Supplementary material