Sage Journals: Discover world-class research

Abstract

Premenstrual syndrome (PMS) and dysmenorrhea, in addition to harming the physical and mental health of women, also disrupt their daily life and quality of life. We aimed to investigate the effects and underlying mechanisms of Curcuma longa (turmeric) and curcumin on PMS and dysmenorrhea. PRISMA guideline 2020 was followed for conducting this systematic review. Comprehensive literature searches were conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Scopus. Finally, 17 articles were found after considering the study’s inclusion and exclusion criteria into account. Data were extracted and entered into an Excel file for further investigation and drew the results. Curcuma longa and curcumin affect PMS and dysmenorrhea through various mechanisms. They inhibit the activity of cyclooxygenase-2 (COX-2) and the production of prostaglandins, thus reducing inflammation and pain. Additionally, curcumin’s antioxidant properties protect against oxidative stress, and lipid peroxidation helps maintain hormonal balance, exert analgesic effects, and relieve the symptoms of PMS and dysmenorrhea. They also insert neurotransmitter modulatory properties, such as increased serotonin and dopamine levels, which may contribute to their antidepressant, and sedative effects. Curcuma longa and curcumin indicated promising therapeutic effects in reducing PMS and dysmenorrhea symptoms due to their anti-inflammatory and antioxidant effects. Although, further well-designed clinical trials are needed to establish their efficacy and optimal dosage.

Keywords

curcumin premenstrual syndrome dysmenorrhea pain

Introduction

Premenstrual syndrome (PMS) and dysmenorrhea are common conditions experienced by many women during their reproductive years.¹ PMS refers to a wide range of physical and emotional symptoms before menstruation, while dysmenorrhea refers to painful menstrual cramps.² The most typical physical and psychological symptoms of PMS in women are dysmenorrhea, exhaustion, irritability, and anxiety.² These conditions can significantly negatively impact a woman’s quality of life, academic performance, and professional efficiency.^2
–4 Various drugs are available for the treatment of PMS and dysmenorrhea, such as non-steroidal anti-inflammatory drugs (NSAIDs), anxiolytic agents, selective serotonin reuptake inhibitors (SSRIs), gonadotropin-releasing hormone (GnRH) agonists, oral contraceptive pills, and spironolactone. However, each has its complications. For example, NSAIDs have many side effects, including headaches, indigestion, and drowsiness.^5,6 Therefore, it becomes necessary to find new treatment strategies and complementary medicines.

There has been growing interest in using natural remedies which are used in the treatment of various diseases due to their antioxidant and anti-inflammatory properties.^7
–9 Curcuma longa (commonly known as turmeric) and its active compound curcumin, had promising effects in managing pain and inflammatory diseases.^10
–12 Curcuma longa, a perennial herbaceous plant native to Southeast Asia, is widely known for its culinary and medicinal uses. It is the primary source of the bright yellow spice called turmeric, which contains various bioactive compounds. Curcumin is the main active component found in turmeric, responsible for its vibrant color and numerous health benefits. It possesses potent anti-inflammatory, antioxidant, and analgesic properties, making it a subject of interest for menstrual health research.^13
–15 So, this study aimed to investigate the effects and underlying mechanisms of Curcuma longa and curcumin on PMS and dysmenorrhea.

Materials and methods

Data sources and search strategy

PRISMA guidelines 2020 were used to develop and conduct this systematic review. An extensive literature search was done in multiple databases, including Web of Science, EMBASE, PubMed, Embase, Cochrane Library, and Scopus, on 6/20/2023. For searching in database records, various keywords were applied. The terms were including: ((“Curcuma” OR “Tumeric” OR “Turmeric” OR “Curcumin” OR “Diferuloylmethane”) AND (“premenstrual syndrome” OR “premenstrual tension” OR “dysmenorrhea” OR “painful menstruation”)), which were taken from the Medical Subject Headings (MeSH).

Study selection

The articles searched in the mentioned databases were imported into the EndNote 20 (released on 30 November 2021) Software, and duplicate records were removed. Two researchers independently screened all the studies found in the databases regarding titles /abstracts. The clinical trial design studies that examined how Curcuma longa and curcumin can impact premenstrual syndrome and dysmenorrhea were included in this systematic review based on the inclusion criteria. Exclusion criteria include not having access to the full texts of the publications, conference articles, and non-English studies. Two researchers attached and investigated the full texts of all included studies after the systematic literature review was finished and studies were screened for inclusion and exclusion criteria. If there is a disagreement or conflict between two investigators, it is usually settled down through discussion.

Data extraction

The data about the first author’s name, the publication date, the setting, the type of study, the sample size, the investigated disorder, the clinical approach and dosage, the time of exposure, and the outcomes were extracted from the publications after they had been reviewed. The extracted data was not included in the study if it had irrelevance to the study’s goal.

Results

Search results, study characteristics of selected studies

The PRISMA flowchart illustrated the included and excluded studies searched in the main databases (Figure 1). In general, we retrieved about 238 articles in the initial search. Out of this number, we removed about 17 articles in EndNote due to duplication. Some other titles/abstracts were also excluded (n = 8); four because of not include desirable data,^16
–19 three because of not having been published in English,^20
–22 and a conference article.²³

Figure 1.

Flow diagram for including studies in the systematic review.

Finally, 17 articles were selected for the final assessment.^6,24
–39 These articles mainly examined outcomes such as cramping pains or disease symptoms before and after the intervention using PMS measurement tools. The studies were conducted mainly in Iran and Indonesia, and some in Brazil, Turkey, and India. Most studies were designed and implemented as RCTs (Table 1).

Table 1.

Characteristics of selected studies of the effect of Curcuma longa and curcumin on PMS and dysmenorrhea.

The first author (reference)	Publication year	Country	Type of study	Sample size	Type of disorder	Clinical approach	Main outcomes
Khayat et al.²⁴	2015	Iran	RCT	70	PMS	Two curcumin capsules (100 mg/12 h) daily for 7 before and until 3 days after menstruation cycles	The total severity of the PMS score had reduced and attenuated the severity of PMS symptoms
Fanaei et al.²⁵	2016	Iran	RCT	70	PMS	Curcumin capsules (100 mg/12 h) were given daily for three successive menstrual cycles, and each cycle ran 10 days	BDNF levels were significantly increased, and mean scores and PMS symptoms were reduced.
Dyawapur et al.²⁶	2018	India	RCT	60	Dysmenorrhoea	1/4–1/2 teaspoon of turmeric administered directly after menstruation 30 ml of content and pain assessed after 20 min	Reduced dysmenorrhoea pain scores
Zoodfekr et al.²⁷	2018	Iran	RCT	40	PMS	100 mg of curcumin two times a day, from 7 days before menstruation until day 3 of period	Decreased prostaglandin E2 levels and no change were seen in levels of prolactin
Krishnamurti et al.²⁸	2020	Indonesia	In silico	-	Dysmenorrhoea	By docked using Autodock Vina in PyRx 0.8 and used turmeric and tamarind bioactive compounds in a single isolated form	Inhibited COX-1/COX-2, stabilizing protein-ligand interaction, and reducing prostaglandin concentration lead to healing dysmenorrhea
Pichardo et al.²⁹	2020	Brazil	RCT	108	PMS	500 mg/12 h started 7 days prior start of the menstruation, and continuing for 2 days after menstruation begins, for three successive menstrual cycles out of four cycles	Indicated analgesic effect and reduced menstrual symptom score
Tabari et al.³⁰	2020	Iran	RCT	74	Dysmenorrhoea	500 mg turmeric extract with two capsules with food for the first 3 days of menstruation was used for two cycles	Pain intensity score and pain duration were reduced.
Utami et al.³¹	2020	Indonesia	Quasi-experimental	32	Dysmenorrhoea	Curcuma longa drinks (turmeric paste is added with 110 ml of water and boiled for 10 min) on the first day of menstruation until the third day twice daily for 100 ccs during menstruation	Dysmenorrhoeal pain was reduced in adolescent girls
Bahrami et al.³²	2021	Iran	RCT	124	PMS	500 mg of capsulated curcuminoid, daily, from 7 days before and until 3 days post menstruation for three successive menstrual cycles	Reduced PSST and pain in women who suffered from both PMS and dysmenorrhea
Hesami et al.⁶	2021	Iran	RCT	128	Primary dysmenorrhea	500 mg of powdered turmeric prescribed for 5, 2 before, and 3 days after the beginning of menstruation	A combination of mefenamic acid and turmeric significantly reduces pain
Okuyan et al.³³	2021	Turkey	RCT	150	Primary dysmenorrhea	1 g/day turmeric powder as a dietary supplement consumed peroral during menstrual bleeding	Reduced nulliparous patients with primary dysmenorrhea
Arabnezhad et al.³⁴	2022	Iran	RCT	76	PMS and dysmenorrhoea	One capsule contains 500 mg of curcuminoid + 5 mg piperine daily, from 7 days before until 3 days after menstruation, for three consecutive menstrual cycles	Increased liver function enzyme test, vitamin D, and did not affect blood glucose
Bahrami et al.³⁵	2022	Iran	RCT	80	PMS and primary dysmenorrhoea	One capsule of 500 mg of curcuminoid + piperine daily, from 7 days before until 3 days after menstruation, for three consecutive menstrual cycles	Curcumin + piperine have a positive effect on serum IgE levels with no changes on serum IL-10 and IL-12 levels
Agarwal and Chaudhary³⁶	2023	India	RCT	60	Primary dysmenorrhea	A single dose of two soft gels of 500 mg of turmeric–boswellia–sesame formulation	Reduced the mean total pain relief and pain intensity
Bahrami et al.³⁷	2023	Iran	RCT	124	PMS and dysmenorrhoea	One capsule included 500 mg of curcuminoid for 10 days over three menstrual cycles	Indicated beneficial impact on cognitive function and memory scores and improved inhibitory control and selective attention
Safitri et al.³⁸	2023	Indonesia	Cross-sectional	76	Menstrual Symptoms Questionnaire	Routine consumption of the turmeric-tamarind herb	Reduced MSQ score, experiencing primary dysmenorrhea and pain
Seyedabadi et al.³⁹	2023	Iran	RCT	124	PMS and dysmenorrhoea	One capsule with 500 mg of curcumin + piperine, daily, from 7 before to 3 days after menstruation for three consecutive menstrual cycles	Curcumin does not significantly affect sleep disorders and pain

↓: reduced; ↑: increase; RCT: randomized clinical trial; PMS: premenstrual syndrome; BDNF: brain-derived neurotrophic factor; COX: cyclooxygenase, PSST: Premenstrual Syndrome Screening Tool; IgE: immunoglobulin E; NRS: Numeric Rating Scale; MSQ; Menstrual Symptoms Questionnaire.

Effects of Curcuma longa (turmeric) and curcumin on PMS and dysmenorrhea

Studies have suggested that curcumin may alleviate several symptoms associated with PMS. The anti-inflammatory properties of curcumin may help reduce breast tenderness, bloating, and abdominal discomfort commonly experienced during the premenstrual phase.⁴⁰ Additionally, curcumin’s ability to modulate neurotransmitters like serotonin may contribute to its potential mood-stabilizing effects, potentially reducing the emotional symptoms of PMS, including irritability, depression, and anxiety.²⁴

Dysmenorrhea is often characterized by severe menstrual pain caused by increased production of inflammatory prostaglandins. Curcumin’s anti-inflammatory and analgesic properties make it a promising natural remedy for managing dysmenorrhea.^5,34 By inhibiting the production of pro-inflammatory mediators, curcumin may help alleviate menstrual cramps and reduce the intensity and duration of pain during menstruation. Some studies have indicated that curcumin’s pain-relieving effects may be comparable to NSAIDs commonly used to manage dysmenorrhea.^14,41

Mechanisms of action of Curcuma longa (turmeric) and curcumin on premenstrual syndrome and dysmenorrhea

Curcuma longa and curcumin affect PMS and dysmenorrhea through various mechanisms, including anti-inflammatory properties, antioxidant properties, analgesic effects, and modulating neurotransmitters. We explain these mechanisms in the following:

Anti-inflammatory properties

Curcumin has been found to exhibit potent anti-inflammatory properties. In PMS and dysmenorrhea, inflammation can contribute to hormonal imbalances and pain. By reducing inflammation, curcumin may help alleviate symptoms associated with these conditions.⁴²

Curcuma longa, commonly known as turmeric, and its active compound, curcumin, have long been recognized for their potent anti-inflammatory properties. Numerous studies have demonstrated the ability of curcumin to reduce inflammation by targeting various molecular pathways involved in the inflammatory response.¹⁴ For example, curcumin has been shown to inhibit the activity of inflammatory enzymes such as cyclooxygenase-2 and inducible nitric oxide synthase (iNOS), leading to a decrease in the production of inflammatory mediators such as prostaglandins and nitric oxide (NO). Additionally, curcumin has been found to suppress the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, which may play critical roles in the initiation and propagation of inflammation.⁴³ Curcumin potentially regulates Mitogen-activated protein kinases (MAPK), Activator Protein 1 (AP-1), the Janus kinase/Signal transducer and activator of transcription (JAK/STAT), and other signaling pathways. It prevents the production of inflammatory mediators.¹⁴ Furthermore, curcumin has been shown to modulate the activation of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2).⁴⁴ In the included articles in this study, curcumin or Curcuma longa, prostaglandin E2, COX-1/COX-2, and serum IL-10 and IL-12 levels were reduced or inhibited due to patient treatment.^27,28,35

Antioxidant properties

Although the exact causes of PMS symptoms are unknown, the hypothesis process complex psycho-somatic disorders processes, including they are probably impacted by oxidative stress. In healthy women, estrogen and progesterone have antioxidant effects; however, pro-oxidant activity is increased in PMS patients, resulting in oxidative damage. Progesterone and allopregnanolone levels are linked to depression in women during the premenstrual phase. Nevertheless, oxidative stress and chronic inflammation may influence the onset of PMS and other gynecological diseases.^45,46 On the other hand, oxidative stress has a crucial role in dysmenorrhea pathophysiology. According to some theories, oxidative stress results from factors that upset the balance between reactive oxygen species (ROS) and antioxidants, such as elevated levels of activated macrophages, iron accumulation, or environmental contaminants. Increased ROS is a significant contributor to the onset of disease, and endometriosis and infertility may be linked to oxidative stress that has spread to the peritoneal environment.⁴⁷ Curcumin can alleviate endometriosis symptoms and prevent the angiogenesis of endometrial lesions due to its antioxidant and anti-inflammatory properties.⁴⁸ According to some studies, ROS or free radicals may encourage endometrial cell growth and adhesion in the peritoneal cavity, which could lead to endometriosis and infertility.

Curcumin, as a bioactive polyphenolic ingredient, possesses potent antioxidant properties, which can help neutralize harmful free radicals in the body. Oxidative stress has been implicated in hormonal imbalances and menstrual pain. By reducing oxidative stress, curcumin may support hormonal balance and reduce symptoms of PMS and dysmenorrhea.^49,50 Curcumin’s antioxidant activity arises from its ability to scavenge free radicals and inhibit the generation of ROS, which are known to contribute to oxidative stress and inflammation. Curcumin increases the levels of glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) activities and reduces the level of malondialdehyde (MDA) and total oxidant status (TOS) in the blood.⁵¹

Moreover, the antioxidant activity of curcumin is associated with triggering several antioxidant enzyme activities, including CAT, glutathione transferase, and heme-oxygenase-1.^52,53 Curcumin can reduce lipid peroxidation, a process in which free radicals damage fats and lipids within the body, further contributing to its antioxidant properties.⁵⁴ A study revealed that bioactive molecules such as curcumin exert antioxidant and anti-inflammatory activity and, by these mechanisms, can improve mood by increasing serotonin and exerting antidepressant, sedative, and analgesic effects in premenstrual syndrome.⁵⁵

Analgesic properties

Pain and cramping are the prevalent symptoms and uncomfortable side effects of PMS and dysmenorrhea.^1,56 Curcumin has been found to exhibit analgesic properties and may help reduce pain by inhibiting inflammatory mediators and modulating pain perception pathways.⁵ Curcumin exhibits its analgesic effects at a cellular level by modulating immune and neuronal cells. This multifaceted compound suppresses pro-inflammatory mediators and enhances endogenous anti-inflammatory mediators. Doing so restores the delicate balance between inflammatory processes that contribute to pain and those that promote healing.⁵⁷ Curcumin inhibits the activity of COX-2, leukotrienes, cytokines, and the secretion of prostaglandins, thus reducing inflammation and pain.⁴⁴ So, they play a crucial role in promoting inflammation and sensitizing pain receptors; thus, by inhibiting their activity, curcumin helps reduce pain sensations.⁴³

Additionally, curcumin has been found to modulate the transmission of pain signals by affecting neurotransmitters such as serotonin, dopamine, and glutamate. These neurotransmitters play a crucial role in transmitting pain-related signals and perceiving pain. Moreover, curcumin reduces neuroinflammation by modulating pro-inflammatory factors and TNF-α.⁵⁸

Furthermore, curcumin’s analgesic properties can also be attributed to its ability to modulate the immune response. Curcumin has been shown to suppress the release of pro-inflammatory cytokines, such as TNF-α and IL-1, which contribute to pain and inflammation.⁵⁹ Curcumin also has been shown to modulate the transmission of pain signals in both peripheral and central pathways of pain and exert anti-inflammatory effects by regulating effects on macrophage and microglia.^60,61 When it comes to modulation at a mechanistic level, curcumin’s actions extend far beyond just modulating neurotransmitters related to pain or blocking transient receptor potential vanilloid type I receptors. It activates pathways involved in cell cycle regulation, apoptosis, mutagenesis, and oncogene expression - all key factors impacting cancer progression.⁵⁸

Modulate neurotransmitters, hormones, and mood regulation

Effects on neurotransmitters

There are several proposed mechanisms by which curcumin and turmeric may modulate neurotransmitters, such as anti-inflammatory, antioxidant activity, and monoamine oxidase (MAO) inhibition.⁶²

Curcumin has been found to possess anti-inflammatory effects. Chronic inflammation in the brain can negatively affect neurotransmitter balance, including adverse effects on norepinephrine, dopamine, and serotonin. So, through suppressing inflammation, curcumin may indirectly support optimal neurotransmitter function and can be used for treating major depression.⁶³ In addition, curcumin is a potent antioxidant, capable of scavenging free radicals and reducing oxidative stress in various parts of the tissues. Oxidative stress can impair neurotransmitter signaling and contribute to neurodegenerative conditions. This situation also leads to mitochondrial dysfunction, consequently disturbing cellular signaling, lipids, and protein functions and disrupting the chemical integrity of the brain. Ultimately, this condition precipitates neuroinflammation, neurotransmitter imbalance, and apoptotic cell death.⁶⁴ By reducing oxidative stress, curcumin may help maintain neurotransmitter balance. Another mechanism of curcumin is to inhibition of MAO activity. MAO is an enzyme that breaks down neurotransmitters such as serotonin, dopamine, and norepinephrine. Inhibiting MAO activity can increase the levels of these neurotransmitters in the brain. Some studies have suggested that curcumin may inhibit MAO activity, thereby increasing the availability of these neurotransmitters and potentially improving mood and cognitive function.⁶³

In this regard, curcumin has been shown to modulate serotonin receptors in the brain, particularly the 5-HT1A receptor. By interacting with these receptors, curcumin may affect serotonin signaling and contribute to its antidepressant and anxiolytic effects.^65,66

Dopamine is another crucial neurotransmitter involved in mood regulation, motivation, and reward. Curcumin has been shown to modulate dopamine levels and dopamine receptor activity in various studies.^67,68

According to research, curcumin also helps neurotrophic factors like brain-derived neurotrophic factor (BDNF) express and function more effectively. In addition to helping synapse plasticity, neurotrophic factors are essential for neurons’ growth, development, and survival. Curcumin might aid in maintaining and properly operating neurotransmitter systems by raising the levels of these components and potentially treating behavioral disorders.⁶⁹

Effects on hormones

Curcumin has been shown to affect hormone levels by influencing several pathways. For example, it may inhibit the enzymes involved in estrogen metabolism, potentially leading to increased estrogen levels. Additionally, curcumin has been found to modulate the production and activity of certain prostaglandins, which are hormone-like substances involved in the menstrual cycle and pain sensation.⁵ Hormonal imbalances, particularly estrogen, and progesterone, are associated with PMS and dysmenorrhea.⁷⁰ Curcumin has been reported to influence hormone levels and their receptors. By modulating hormone signaling, curcumin may help regulate mood and mitigate hormonal-related symptoms.¹⁴

Activation of the corticotropin-releasing hormone system by high-stress levels inhibits the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which inhibit follicle development. Stress-related hormones, including cortisol and adrenaline, can elevate prostaglandin synthesis and lead to dysmenorrhea.^71,72

Curcumin also inhibited stress by reductions in brain-derived neurotrophic factor (BDNF) protein levels and phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in animal models’ hippocampus.⁷³ Curcumin is considered an effective inhibitor of adrenocorticotropic hormone and angiotensin II-stimulated cortisol secretion.⁷⁴

PMS is often associated with mood swings, psycho-emotional, irritability, and depression.⁷⁵ Curcumin has been investigated for its potential antidepressant and mood-stabilizing effects. It can regulate anxiety-like behavior and stress in patients.⁷⁶ It also may modulate neurotransmitters like serotonin and dopamine, which play crucial roles in mood regulation. By positively influencing mood, curcumin could help alleviate PMS symptoms. Curcumin has been shown to influence various neurotransmitters in the brain, including serotonin, dopamine, and gamma-aminobutyric acid (GABA). These neurotransmitters play essential roles in mood regulation and emotional well-being. By modulating their levels or activity, curcumin may help stabilize mood and alleviate emotional symptoms associated with PMS and dysmenorrhea.^77
–79

Although there is still no strong evidence, melatonin as a pineal hormone is an effective and safe treatment in reducing PMS symptoms.⁸⁰ Melatonin aids in sleep, and the timing of your internal 24-h clock, or circadian rhythms, has a complex role in the immune system, which also has anti-inflammatory and antioxidant properties.⁸¹ Melatonin might improve hippocampus cell survival by reducing oxidative stress, upregulating B-cell lymphoma 2 (Bcl-2), downregulating Sirtuin 2 (SIRT2) expression, and decreasing oxidative stress.⁸² Curcumin, the Curcuma longa plant’s principal active ingredient, has a variety of medicinal uses, including neuroprotection. It prevents neuronal loss, structural changes, and deleterious effects of sleep deprivation.⁸³

Moreover, curcumin and melatonin directly affect activity and receptor expression in endometrial tissue, endometrial lesions’ invasion, apoptosis, adhesion, and angiogenesis. Regarding dietary disease management and prevention for women, curcumin use may be promising for women’s genital disorders.^84,85 Clinical and experimental evidence indicated that bioactive compounds such as curcumin not only have anti-inflammatory and antioxidant properties but also revealed other activities such as serotonergic, GABA-A receptor agonist, antidepressant, analgesic, and sedative effects and insert complex physical and psychological impacts on relieving PMS and dysmenorrheal symptoms.^55,86 Nevertheless, despite the promising evidence of melatonin in reducing the symptoms of PMS and dysmenorrhea, a study showed that curcumin has no effect on insomnia in young women with these disorders.³⁹ Therefore, more in-depth evidence is needed to determine curcumin’s beneficial effects on melatonin levels and, subsequently, its effect on insomnia in women with PMS and dysmenorrhea.

In general, the possible mechanisms of the effect of Curcuma longa and curcumin on the symptoms of PMS and dysmenorrhea in women are illustrated schematically and briefly in Figure 2.

Figure 2.

Main possible mechanisms of Curcuma longa and curcumin on PMS and dysmenorrhea (created in: https://www.biorender.com/).

Bioavailability and metabolism of curcumin

One of the main problems is thought to be curcumin’s bioavailability. The poor intestinal and transcellular permeability, instability at alkaline phosphatase pH, and rapid systemic clearance or metabolism and systemic elimination all associated with curcumin’s low oral bioavailability.⁸⁷ The interaction between the liver’s extensive reductive and conjugative metabolism and the small intestine’s poor absorption significantly lowers oral bioavailability. In general, curcumin has a low oral bioavailability because of the small intestine’s relatively low absorption rate, the liver’s extensive reductive and conjugative metabolism, and the gall bladder’s role in elimination. The curcumin’s binding to enterocyte proteins, which can change its structure, worsens the poor bioavailability.⁸⁸ Coadministration with other agents (nanoparticles, micro/nanoemulsions, liposomes, piperine, solid dispersions, and incorporation into micelles), modulation of route and medium, complexed/encapsulated curcumin, solid and liquid oral delivery systems and structural modifications of curcumin are some current strategies for improving its bioavailability.^89,90 The outcomes of clinical trials using various curcumin delivery techniques demonstrated that increased therapeutic efficacy is associated with improved bioavailability.⁹⁰ A large number of curcumin formulations have been tested to increase bioavailability, and only some of them have been used commercially, mostly as dietary supplements.⁹⁰

Conclusion

Curcuma longa and its active compound curcumin may have beneficial effects on PMS and dysmenorrhea, due to its anti-inflammatory, antioxidant, and analgesic properties, and can be effective in the treatment of PMS and dysmenorrhea. Although, further well-designed clinical trials are needed to establish their efficacy and optimal dosage. It is important to consult with a healthcare professional before incorporating turmeric or curcumin supplements into a treatment regimen, especially for individuals with existing medical conditions or those taking other medications. Nonetheless, the potential of curcumin as a natural alternative for managing PMS and dysmenorrhea holds promise and warrants further investigation.

Supplemental Material

sj-docx-1-pev-10.1177_22840265231219331 – Supplemental material for Effects of Curcuma longa (turmeric) and curcumin on the premenstrual syndrome and dysmenorrhea: A systematic review

Supplemental material, sj-docx-1-pev-10.1177_22840265231219331 for Effects of Curcuma longa (turmeric) and curcumin on the premenstrual syndrome and dysmenorrhea: A systematic review by Zahra Shabanian Boroujeni, Saeid Heidari-Soureshjani and Catherine MT Sherwin in Journal of Endometriosis and Pelvic Pain Disorders

Footnotes

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Saeid Heidari-Soureshjani

Catherine MT Sherwin

Supplemental material

Supplemental material for this article is available online.

References

Gudipally

Sharma

. Premenstrual syndrome. StatPearls. Treasure Island, FL: StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK560698/ (2023, accessed 18 July 2022).

Abbas

Usman

Ahmed

, et al. Physical and psychological symptoms associated with premenstrual syndrome and their impact on the daily routine of women in a low socioeconomic status locality. Cureus 2020; 12: e10821.

Bilir

Yıldız

Yakın

, et al. The impact of dysmenorrhea and premenstrual syndrome on academic performance of college students, and their willingness to seek help. Turk J Obstet Gynecol 2020; 17: 196–201.

Al-Shahrani

Miskeen

Shroff

, et al. Premenstrual syndrome and its impact on the quality of life of female medical students at Bisha University, Saudi Arabia. J Multidiscip Healthc 2021; 14: 2373–2379.

Marjoribanks

Ayeleke

Farquhar

, et al. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev 2015; 2015: Cd001751.

Hesami

Kavianpour

Rashidi Nooshabadi

, et al. Randomized, double-blind, placebo-controlled clinical trial studying the effects of Turmeric in combination with mefenamic acid in patients with primary dysmenorrhoea. J Gynecol Obstet Hum Reprod 2021; 50: 101840.

Altememy

Patra

Hussam

, et al. Determination and evaluation of total antioxidant capacity of methanolic extracts of Quercus brantii, Thymbra spicata, Citrullus colocynthis. Adv Life Sci 2022; 9: 372–379.

Khaledifar

Farsani

MRK

Raeisi

. Berberine efficacy against Doxorubicin-induced cardiotoxicity: a systematic review. J Herbmed Pharmacol 2023; 12: 187–193.

Raeisi

Heidarian

, et al. Bromelain inhibitory effect on colony formation: an In vitro Study on human AGS, PC3, and MCF7 cancer cells. J Med Signals Sens 2019; 9: 267.

10.

Welz

Emberger-Klein

Menrad

. Why people use herbal medicine: insights from a focus-group study in Germany. BMC Complement Altern Med 2018; 18: 92.

11.

Ghahfarrokhi

Heidari-Soureshjani

Talebi-Boroujeni

, et al. Effect and mechanism of curcumin on bone loss and osteoporosis: a systematic review. Curr Tradit Med 2023; 9: 145–154.

12.

Sherwin

Heidari-Soureshjani

. Effects and mechanisms of medicinal plants on healing scars: a systematic review. Curr Tradit Med 2022; 8: 69–80.

13.

Varma

A.C K

Jude

Varghese

, et al. Chapter 2 - Curcuma longa. In: Amalraj

Kuttappan

Varma

A.C K

, et al. (eds) Herbs, spices and their roles in nutraceuticals and functional foods. Cambridge, Massachusetts: Academic Press, 2023, pp. 15–30.

14.

Peng

Dong

, et al. Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug Des Dev Ther 2021; 15: 4503–4525.

15.

Paknia

Parchami

Nasry

, et al. Therapeutic activities and biological effects of curcumin, as a natural multi-target compound, on human health: a minireview. J Shahrekord Univ Med Sci 2022; 24: 145–152.

16.

Ria

Ola

CYI

Palalangan

. The difference of effectiveness of ginger warm compress and consumption of acidic turmeric on decreasing primary menstrual pain scale. J Matern Child Health 2021; 6: 285–294.

17.

Sali

Risal

. The effect of drinking turmeric stew towards reducing dysmenorrheal pain scale on students of senior high school 1 of East Pamona, Poso Regency. J Ilmu Kesehatan 2021; 9: 106–117.

18.

Gustina

Safitri

. The effects of turmeric acid consumption and yoga on young women’s dysmenorrhea. J EduHealth 2022; 13: 498–504.

19.

Makiyah

Anggraini

. The effectiveness of giving tumeric tamarind in reducing menstrual pain (dismenoroe) in young girls at Mts Al-Muqowamah. Asian J Community Serv 2023; 2: 23–34.

20.

Peng

Dong

Jiang

, et al. [Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea]. Zhongguo Zhong yao za zhi 2023; 48: 649–659.

21.

Sari

. The effectivity differentiation of honey and tamarind turmeric drink on decreasing menstrual pain. University of Muhammadyah Malang (It’s Doctoral dissertation), 2019.

22.

Astari

. Effect of warm compress, ginger drink and turmeric drink on the decrease in the degree of menstrual pain. J Kebidanan 2020; 10: 67–73.

23.

Utari

. Effect turmeric acid consumption on the menstrual pain in young women in Al-Hamid Islamic boarding school Jakarta and Nur medina Islamic boarding school Tangerang. In: First international conference on health development, Jakarta, 2019.

24.

Khayat

Fanaei

Kheirkhah

, et al. Curcumin attenuates severity of premenstrual syndrome symptoms: a randomized, double-blind, placebo-controlled trial. Complement Ther Med 2015; 23: 318–324.

25.

Fanaei

Khayat

Kasaeian

, et al. Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. Neuropeptides 2016; 56: 25–31.

26.

Dyawapur

Patil

Metri

. Effectiveness of cinnamon tea and turmeric water for reducing dysmenorrhoea among degree girls. Int J Sci Healthc Res 2018; 3: 88–92.

27.

Zoodfekr

Matin Homaee

Tarverdizadeh

. The effect of an aerobic training course and consumption of curcumin on prostaglandin E2 and prolactin levels in women with premenstrual syndrome. Iran J Endocrinol Metab 2018; 19: 444–451.

28.

Krisnamurti

Bare

Amin

, et al. Combination of curcumin from curcuma longa and procyanidin from Tamarindus indica in inhibiting cyclooxygenases for primary dysmenorrhea therapy: in silico study. Biointerface Res Appl Chem 2020; 11: 7460–7467.

29.

Pichardo

Liborio-Kimura

Caballero

MdPE

, et al. ESCAPE pain trial-The effects of Curcumin in pain relief in women diagnosed with primary dysmenorrhea: a triple blinded, placebo-controlled, phase II, randomized clinical trial protocol. Princ Pract Clin Res 2020; 6: 25–32.

30.

Tabari

Kheirkhah

Mojab

, et al. An investigation of the effect of curcumin (turmeric) capsule on the severity and duration of dysmenorrhea in students of Iran University of Medical Sciences. J Evol Med Dent Sci 2020; 9: 3444–3451.

31.

Utami

Damayanti

Rodiah

. The effectiveness of curcuma longa drink in decreasing the intensity of dysmenorrhea. Biomed Pharmacol J 2020; 13: 2055–2060.

32.

Bahrami

Zarban

Rezapour

, et al. Effects of curcumin on menstrual pattern, premenstrual syndrome, and dysmenorrhea: a triple-blind, placebo-controlled clinical trial. Phytother Res 2021; 35: 6954–6962.

33.

Okuyan

Günakan

Halit

, et al. The effect of turmeric on primary dysmenorrhea: prospective case-control study. J Surg Med 2021; 5: 715–717.

34.

Arabnezhad

Mohammadifard

Rahmani

, et al. Effects of curcumin supplementation on vitamin D levels in women with premenstrual syndrome and dysmenorrhea: a randomized controlled study. BMC Complement Med Ther 2022; 22: 19.

35.

Bahrami

Mohammadifard

Rajabi

, et al. Effects of curcumin-piperine supplementation on systemic immunity in young women with premenstrual syndrome and dysmenorrhea: a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 2022; 278: 131–136.

36.

Agarwal

Chaudhary

. Effect of turmeric-Boswellia-sesame formulation in menstrual cramp pain associated with primary dysmenorrhea: a double-blind, randomized, placebo-controlled study. J Clin Med 2023; 12: 3968.

37.

Bahrami

Jafari-Nozad

Karbasi

, et al. Efficacy of curcumin on cognitive function scores in women with premenstrual syndrome and dysmenorrhea: a triple-blind, placebo-controlled clinical trial. Chin J Integr Med 2023; 29: 387–393.

38.

Safitri

Gustina

. Effect of routine consumption of turmeric-tamarind herb on dysmenorrhea among adolescent girls. Embrio: J Kebidanan 2023; 15: 41–48.

39.

Seyedabadi

Hoseini

Ferns

, et al. Effects of curcumin supplementation on insomnia and daytime sleepiness in young women with premenstrual syndrome and dysmenorrhea: a randomized clinical trial. Avicenna J Phytomed 2023; 13: 585–596

40.

Siminiuc

Ţurcanu

. Impact of nutritional diet therapy on premenstrual syndrome. Front Nutr 2023; 10: 1079417.

41.

Y-S

Chen

T-H

Weng

, et al. Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharmacother 2021; 141: 111888.

42.

Barcikowska

Rajkowska-Labon

Grzybowska

, et al. Inflammatory markers in dysmenorrhea and therapeutic options. Int J Environ Res Public Health 2020; 17: 191.

43.

Córdova

Drobnic

Noriega-González

, et al. Is Curcumine useful in the treatment and prevention of the tendinopathy and myotendinous junction injury? A scoping review. Nutrients 2023; 15 : 384.

44.

Tan

Poulose

Raveendran

, et al. Regulation of the expression of cyclooxygenases and production of prostaglandin I₂ and E₂ in human coronary artery endothelial cells by curcumin. J Physiol Pharmacol 2011; 62: 21–28.

45.

Granda

Szmidt

Kaluza

. Is premenstrual syndrome associated with inflammation, oxidative stress and antioxidant status? A systematic review of case-control and cross-sectional studies. Antioxidants 2021; 10: 604.

46.

Chen

Gao

, et al. Allopregnanolone in mood disorders: mechanism and therapeutic development. Pharmacol Res 2021; 169: 105682.

47.

Gupta

Agarwal

Krajcir

, et al. Role of oxidative stress in endometriosis. Reprod BioMed Online 2006; 13: 126–134.

48.

Arablou

Kolahdouz-Mohammadi

. Curcumin and endometriosis: review on potential roles and molecular mechanisms. Biomed Pharmacother 2018; 97: 91–97.

49.

Szmidt

Granda

Sicinska

, et al. Primary dysmenorrhea in relation to oxidative stress and antioxidant status: a systematic review of case-control studies. Antioxidants 2020; 9: 994.

50.

Hewlings

Kalman

. Curcumin: a review of its effects on human health. Foods 2017; 6: 92.

51.

Maithili Karpaga Selvi

Sridhar

Swaminathan

, et al. Curcumin attenuates oxidative stress and activation of redox-sensitive kinases in high fructose- and high-fat-fed male wistar rats. Sci Pharm 2015; 83: 159–175.

52.

Iqbal

Sharma

Okazaki

, et al. Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol 2003; 92: 33–38.

53.

Motterlini

Foresti

Bassi

, et al. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000; 28: 1303–1312.

54.

Alizadeh

Kheirouri

. Curcumin reduces malondialdehyde and improves antioxidants in humans with diseased conditions: a comprehensive meta-analysis of randomized controlled trials. BioMedicine 2019; 9: 23.

55.

Sultana

Rahman

Heyat

MBB

, et al. Role of inflammation, oxidative stress, and mitochondrial changes in premenstrual psychosomatic behavioral symptoms with anti-inflammatory, antioxidant herbs, and nutritional supplements. Oxid Med Cell Longev 2022; 2022: 3599246.

56.

Itani

Soubra

Karout

, et al. Primary dysmenorrhea: pathophysiology, diagnosis, and treatment updates. Korean J Fam Med 2022; 43: 101–108.

57.

Boonrueng

Wasana

PWD

Hasriadi , et al. Combination of curcumin and piperine synergistically improves pain-like behaviors in mouse models of pain with no potential CNS side effects. Chin Med 2022; 17: 119.

58.

Hasriadi Dasuni Wasana

Vajragupta

, et al. Mechanistic insight into the effects of curcumin on neuroinflammation-driven chronic pain. Pharmaceuticals 2021; 14: 777.

59.

Abushukur

Knackstedt

. The impact of supplements on recovery after peripheral nerve injury: a review of the literature. Cureus 2022; 14: e25135.

60.

Dasuni Wasana

Hasriadi Muangnoi

, et al. Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain. Sci Rep 2022; 12: 9713.

61.

Han

Lee

Jeong

, et al. Analgesic effects of intrathecal curcumin in the rat formalin test. Korean J Pain 2012; 25: 1–6.

62.

Kulkarni

Dhir

. An overview of curcumin in neurological disorders. Indian J Pharm Sci 2010; 72: 149–154.

63.

Kulkarni

Dhir

Akula

. Potentials of curcumin as an antidepressant. Scientific World Journal 2009; 9: 1233–1241.

64.

Singh

Kukreti

Saso

, et al. Oxidative stress: a key modulator in neurodegenerative diseases. Molecules 2019; 24: 1583.

65.

Lopresti

. Potential role of curcumin for the treatment of major depressive disorder. CNS Drugs 2022; 36: 123–141.

66.

Chen

, et al. Sub-acute treatment of curcumin derivative J147 ameliorates depression-like behavior through 5-HT(1A)-mediated cAMP signaling. Front Neurosci 2020; 14: 701.

67.

Kumar

Antony

Gireesh

, et al. Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats. J Biomed Sci 2010; 17: 43.

68.

Ramaholimihaso

Bouazzaoui

Kaladjian

. Curcumin in depression: potential mechanisms of action and current evidence-a narrative review. Front Psychiatry 2020; 11: 572533.

69.

Sarraf

Parohan

Javanbakht

, et al. Short-term curcumin supplementation enhances serum brain-derived neurotrophic factor in adult men and women: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutr Res 2019; 69: 1–8.

70.

Bernardi

Lazzeri

Perelli

, et al. Dysmenorrhea and related disorders. F1000Res 2017; 6: 1645.

71.

Ansong

Arhin

Cai

, et al. Menstrual characteristics, disorders and associated risk factors among female international students in Zhejiang Province, China: a cross-sectional survey. BMC Women’s Health 2019; 19: 35.

72.

Wang

, et al. Stress and dysmenorrhoea: a population based prospective study. Occup Environ Med 2004; 61: 1021–1026.

73.

Tie

, et al. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Res 2006; 1122: 56–64.

74.

Enyeart

Liu

Enyeart

. Curcumin inhibits ACTH- and angiotensin II-stimulated cortisol secretion | Ca(v)3.2 current. J Nat Prod 2009; 72: 1533–1537.

75.

Ojezele

Eduviere

Adedapo

, et al. Mood swing during menstruation: confounding factors and drug use. Ethiop J Health Sci 2022; 32: 681–688.

76.

Aubry

Khandaker

Ravenelle

, et al. A diet enriched with curcumin promotes resilience to chronic social defeat stress. Neuropsychopharmacology 2019; 44: 733–742.

77.

Kulkarni

Bhutani

Bishnoi

. Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 2008; 201: 435–442.

78.

Cui

, et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain research 2007; 1162: 9–18.

79.

Liu

Fan

Ding

, et al. Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines. Sci Rep 2017; 7: 46654.

80.

Yin

Zhang

Guo

, et al. Melatonin for premenstrual syndrome: a potential remedy but not ready. Front Endocrinol 2022; 13: 1084249.

81.

Cho

Bhutani

Kim

, et al. Anti-inflammatory effects of melatonin: a systematic review and meta-analysis of clinical trials. Brain Behav Immun 2021; 93: 245–253.

82.

Keskin-Aktan

Akbulut

Yazici-Mutlu

, et al. The effects of melatonin and curcumin on the expression of SIRT2, Bcl-2 and Bax in the hippocampus of adult rats. Brain Res Bull 2018; 137: 306–310.

83.

Erfanizadeh

Noorafshan

Namavar

, et al. Curcumin prevents neuronal loss and structural changes in the superior cervical (sympathetic) ganglion induced by chronic sleep deprivation, in the rat model. Biol Res 2020; 53: 31.

84.

Vallée

Lecarpentier

. Curcumin and endometriosis. Int J Mol Sci 2020; 21: 2440.

85.

Mosher

Tsoulis

Lim

, et al. Melatonin activity and receptor expression in endometrial tissue and endometriosis. Hum Reprod 2019; 34: 1215–1224.

86.

Talebpour

Mohammadifard

Zare Feyzabadi

, et al. Effect of curcumin on inflammatory biomarkers and iron profile in patients with premenstrual syndrome and dysmenorrhea: a randomized controlled trial. Physiol Rep 2023; 11: e15763.

87.

Hegde

Girisa

BharathwajChetty

, et al. Curcumin formulations for better bioavailability: what we learned from clinical trials thus far? ACS Omega 2023; 8: 10713–10746.

88.

Dei Cas

Ghidoni

. Dietary curcumin: correlation between bioavailability and health potential. Nutrients 2019; 11: 2147.

89.

Prasad

Tyagi

Aggarwal

. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat 2014; 46: 2–18.

90.

Tabanelli

Brogi

Calderone

. Improving curcumin bioavailability: current strategies and future perspectives. Pharmaceutics 2021; 13: 1715.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.03 MB