Examining the Impact of Phytoestrogens Supplementation on the Gene Expression, and Premenstrual Syndrome in Primenopausal Women

Examining the Impact of Phytoestrogens Supplementation on the Gene Expression and Premenstrual Syndrome in Perimenopausal Women Aged 40-55 in Jordan

This randomized, double-blind, placebo-controlled clinical trial investigated the effects of flaxseed-derived phytoestrogen supplementation on selected gene-expression markers and premenstrual syndrome (PMS) severity among perimenopausal women aged 40-55 years in Jordan. Participants received either a flaxseed lignan extract providing 100 mg of lignans daily or a matched placebo for 12 weeks. Gene expression and PMS severity were assessed at baseline and at the end of the intervention to examine the potential effects of phytoestrogen supplementation on selected molecular markers and menstrual-related symptoms.

Study Overview

• Status: Enrolling by invitation
• Conditions: Apparently Healthy and Not Receiving Hormonal Therapy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: SDG lignans

Detailed Description

The menopausal transition is a natural biological process characterized by progressive changes in ovarian function, hormonal fluctuations, and alterations in menstrual patterns. During this transition, premenstrual symptoms may persist or change in severity, potentially affecting women's physical and psychological well-being and daily functioning.

Phytoestrogens are plant-derived compounds that share structural similarities with endogenous estrogens and may interact with estrogen receptors, exerting weak estrogenic or anti-estrogenic effects depending on the hormonal environment. Flaxseed is a rich dietary source of lignans, including secoisolariciresinol diglucoside, which can be metabolized by intestinal bacteria into bioactive enterolignans.

This randomized, double-blind, placebo-controlled trial evaluated the effects of daily flaxseed-derived phytoestrogen supplementation on selected gene-expression markers and premenstrual syndrome severity among perimenopausal women aged 40-55 years in Jordan. Participants received either a flaxseed lignan extract providing 100 mg of lignans daily or a matched microcrystalline-cellulose placebo for 12 weeks. The expression of FSTL1 and TGFB1 was assessed using buccal-cell samples collected at baseline and at the end of the intervention. Premenstrual symptoms were evaluated using the validated Arabic Premenstrual Syndrome Scale.

The findings may contribute to understanding the potential effects of flaxseed-derived phytoestrogens on selected molecular markers and premenstrual symptoms among women undergoing the menopausal transition and may inform future nutrition research in this population.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Jordan
  • Amman Governorate
    • Amman, Amman Governorate, Jordan, 11942
      • the university of Jordan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Jordanian women aged 40-55 years
• Regular menstrual cycles during the 90 days preceding enrollment
• Body mass index between 19.0 and 29.9 kg/m²
• Apparently healthy

Exclusion Criteria:

• Pregnancy or lactation
• Current use of hormone replacement therapy or hormonal contraceptives
• Diagnosis of a chronic metabolic, cardiovascular, hepatic, renal, autoimmune, or malignant disease
• History of gynecological disorders or gynecological surgery
• Use of dietary supplements or adherence to a special diet during the 90 days preceding enrollment
• Habitual consumption of flaxseed or use of phytoestrogen supplements
• Active bowel disease or malabsorption syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Microcrystalline cellulose (Placebo), taken orally once daily for 12 weeks. The capsule is matched in size, color, and taste to the active phytoestrogen supplement.	Dietary supplement: Placebo; Microcrystalline cellulose (Placebo), taken orally once daily for 12 weeks. The capsule is matched in size, color, and taste to the active SDG supplement.
Experimental: Intevention SDG lignans; Dietary Supplement: SDG lignans phytoestrogen 100 mg SDG (Active Ingredient), taken orally once daily for 12 weeks	Dietary supplement: SDG lignans; SDG lignans phytoestrogen 100 mg SDG (Active Ingredient), taken orally once daily for 12 weeks; Other Names: flax seed extract

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold Change From Baseline in FSTL1 Gene Expression	Outcome Measure Description: FSTL1 gene expression is quantified in buccal-cell samples using quantitative real-time polymerase chain reaction and normalized to GAPDH expression. The fold change from baseline to Week 12 is calculated using the 2^-ΔΔCt method. A fold-change value of 1 indicates no change, a value greater than 1 indicates increased expression, and a value less than 1 indicates decreased expression.	Time Frame: Baseline (Week 0) and End of Intervention (Week 12)
Fold Change From Baseline in TGFB1 Gene Expression	Outcome Measure Description: TGFB1 gene expression is quantified in buccal-cell samples using quantitative real-time polymerase chain reaction and normalized to GAPDH expression. The fold change from baseline to Week 12 is calculated using the 2^-ΔΔCt method. A fold-change value of 1 indicates no change, a value greater than 1 indicates increased expression, and a value less than 1 indicates decreased expression.	(Week 0) and end of intervention (Week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Mean Physical-Symptom Domain Score on the Arabic Premenstrual Syndrome Scale	The Arabic Premenstrual Syndrome Scale includes 23 items rated from 0 (no symptoms) to 3 (severe symptoms). The physical-symptom domain comprises 10 items, and its score is calculated as the mean of the item responses. The domain score ranges from 0 to 3, with higher scores indicating worse physical symptoms. Change from baseline is calculated as the Week 12 score minus the baseline score and can range from -3 to +3. Negative change values indicate	Time Frame: Baseline (Week 0) and End of Intervention (Week 12)
Change From Baseline in the Mean Psychological-Symptom Domain Score on the Arabic Premenstrual Syndrome Scale	Outcome Measure Description: The Arabic Premenstrual Syndrome Scale includes 23 items rated from 0 (no symptoms) to 3 (severe symptoms). The psychological-symptom domain comprises 12 items, and its score is calculated as the mean of the item responses. The domain score ranges from 0 to 3, with higher scores indicating worse psychological symptoms. Change from baseline is calculated as the Week 12 score minus the baseline score and can range from -3 to +3. Negative change values indicate improvement	Baseline (Week 0) and end of intervention (Week 12)
Change From Baseline in the Impairment-of-Functioning Domain Score on the Arabic Premenstrual Syndrome Scale	Outcome Measure Description: The impairment-of-functioning domain of the Arabic Premenstrual Syndrome Scale evaluates the extent to which premenstrual symptoms interfere with functioning. The domain score ranges from 0 to 3, with higher scores indicating greater functional impairment and therefore a worse outcome. Change from baseline is calculated as the Week 12 score minus the baseline score and can range from -3 to +3. Negative change values indicate improvement.	Baseline (Week 0) and end of intervention (Week 12)

Collaborators and Investigators

• Sponsor: University of Jordan

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Actual): May 25, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: phytoestrogen, flaxseed, SDG lignans, perimenopause, PMS, gene expression
• Additional Relevant MeSH Terms: Lipids; Plant Preparations; Biological Products; Complex Mixtures; Plant Oils; Oils; Fats; Fats, Unsaturated; Linseed Oil
• Other Study ID Numbers: 353/2025; 2025-150/2024 (Other Grant/Funding Number: the university of Jordan); 32152/4/1/3 (Other Identifier: Jordanian food and drug administration)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No