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

Examining the Impact of Phytoestrogens Supplementation and on the Gene Expression of Anti-Müllerian Hormone, Its Receptor, and Premenstrual Syndrome in Primenopausal Women Aged 40-55 in Jordan

This randomized, double-blind, placebo-controlled clinical trial aims to investigate the effect of flaxseed-derived phytoestrogen supplementation on gene expression of Anti-Müllerian Hormone (AMH) and its receptor (AMHR2), as well as the experience and severity of premenstrual syndrome (PMS), among perimenopausal women aged 40-55 years in Jordan. Participants will receive either flaxseed phytoestrogen extract (secoisolariciresinol diglucoside, SDG) or placebo for 12 weeks. Changes in gene expression and PMS severity will be assessed at baseline and post-intervention to explore the potential role of phytoestrogens in modulating ovarian aging 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

Menopause is a natural biological transition characterized by progressive ovarian aging, hormonal fluctuations, and changes in menstrual patterns. Anti-Müllerian Hormone (AMH) and its receptor (AMHR2) play central roles in ovarian folliculogenesis and are considered reliable biomarkers of ovarian reserve and reproductive aging. Reduced AMH levels have been associated with earlier onset of menopause.

Phytoestrogens are plant-derived compounds structurally similar to endogenous estrogens and are capable of interacting with estrogen receptors, exerting weak estrogenic or anti-estrogenic effects depending on the hormonal milieu. Flaxseed is one of the richest dietary sources of lignans, particularly secoisolariciresinol diglucoside (SDG), which is metabolized into bioactive enterolignans.

This study is designed as a randomized, double-blind, placebo-controlled trial to evaluate the effect of daily SDG supplementation on AMH and AMHR2 gene expression and on the experience and severity of premenstrual syndrome in perimenopausal women aged 40-55 years. Participants will be randomly assigned to receive either SDG capsules (100 mg/day) or placebo for 12 weeks. Gene expression will be assessed using salivary samples collected at baseline and post-intervention. PMS severity will be evaluated using a validated Premenstrual Syndrome Scale.

Findings from this trial may contribute to understanding the role of dietary phytoestrogens in modulating reproductive aging and menstrual-related symptoms and may support future development of personalized nutritional strategies for women approaching menopause.

• Study Type: Interventional
• Enrollment (Estimated): 70
• 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:

Women aged 40-55 years Jordanian nationality Body mass index (BMI) between 19 and 29.9 kg/m² Apparently healthy and not receiving hormonal therapy -

Exclusion Criteria:

Pregnancy or lactation Use of hormonal replacement therapy or hormonal contraceptives Diagnosis of chronic metabolic, cardiovascular, liver, kidney, autoimmune, or malignant disease History of gynecological disorders or surgeries Use of dietary supplements or special diets within the previous 3 months Habitual consumption of flaxseed or phytoestrogen supplements Active bowel disease or malabsorption syndrome

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• 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	Time Frame
Change in Gene Expression	Time Frame: Baseline (Week 0) and End of Intervention (Week 12)

Secondary Outcome Measures

Outcome Measure	Time Frame
change of PMS severity scale	Time Frame: 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 (Estimated): January 2, 2026
• Study Completion (Estimated): February 20, 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): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

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