Clinical trial NCT06209697: Effect of Red Clover on Menopause Symptoms and Lipid Profile
Official title: Isoflavones Obtained From Red Clover Improves Both Dyslipidemia and Menopausal Symptoms in Menopausal Women: a Prospective Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menopause
Keywords: menopause, hyperlipidemia, red clover
Lead sponsor: Medipol University
Sponsor class: OTHER
First posted: 2024-01-17
Enrollment: 82
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study included postmenopausal women who had naturally entered menopause and had applied to the outpatient clinics of Istanbul Medipol University Internal Medicine or Gynecology Departments with symptoms of menopause. Other inclusion criteria were: having a history of amenorrhea for at least 12 months, being aged 45-55, having received a diagnosis of dyslipidemia (at the present admission or within the past 3 months), not receiving treatment for dyslipidemia, absence of other chronic diseases, having a follicle stimulating hormone level of \>40 pg/mL and having a body mass index (BMI) of \<30 kg/m2.The subjects were divided into two groups: red clover and placebo groups.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this clinical trial is to investigate the effects of red clover isoflavones on menopausal symptoms and lipid profile in menopausal females.This prospective randomized, double-blind, placebo-controlled study included postmenopausal women with dyslipidemia. The red clover group received 40 mg isoflavone red clover capsule twice daily for 6 months, while placebo was 40 mg starch capsules, twice daily. Data were collected at baseline, 3 months and 6 months. The study was completed with 75 subjects \[red clover (n = 39), placebo (n = 36)\]. Menopause Rating Scale (MRS) was applied to calculate subdimension and total scores. Blood lipid profile, including total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels were measured.

Detailed description: The goal of this clinical trial is to investigate the effects of red clover isoflavones on menopausal symptoms and lipid profile in menopausal females. This was a prospective, randomized, double-blind, placebo-controlled study conducted between March 2022 and September 2023 in the Departments of Gynecology and Internal Medicine of Medipol University Hospital, Istanbul, Turkey. The subjects were divided into two groups: red clover and placebo groups. For the randomization process, patients were provided with slips of paper bearing numbers starting from 1, assigned based on the order of admission by the admitting physician. Subsequently, they were directed to the appropriate nurse. The outpatient clinic nurse assigned red clover treatment to subjects with an odd-numbered slip and placebo to those with an even-numbered slip. The nurse documented the medication assigned to each patient, while the researchers and subjects remained blinded to this information. Red clover (Promensil, PharmaCare Europe Ltd., UK) and placebo (starch capsules) were administered orally twice a day with an interval of 12 hours for a total period of 6 months. Red clover capsules contained 40 mg of standardized red clover isoflavones in each capsule \[genistein (1 mg), daidzein (1 mg), biochanin A (23 mg) and biochanin B (formononetin, 15 mg)\]. Placebo capsules were ordered to be prepared with the same color, taste and smell as the red cover capsules. The patients' total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels were measured using the enzymatic colorimetric method (Hitachi 747 autoanalyzer; Germany) from antecubital venous blood samples taken at 8 AM after a 12-hour overnight fast at baseline, at 3-month follow-up and at 6-month follow-up. The severity of menopausal symptoms was assessed utilizing the Menopause Rating Scale (MRS). Data were collected at baseline, 3 months and 6 months. The study was completed with 75 subjects \[red clover (n = 39), placebo (n = 36)\].

Eligibility criteria: Inclusion Criteria:

History of amenorrhea for at least 12 months

Being aged 45-55

Having received a diagnosis of dyslipidemia (at the present admission or within the past 3 months)

Not receiving treatment for dyslipidemia

Absence of other chronic diseases

Follicle stimulating hormone level of \>40 pg/mL

Body mass index (BMI) of \<30 kg/m2

Exclusion Criteria:

Currently or previously undergoing hormone replacement therapy (either in the past, immediately before, or during the study)

Using any phytotherapeutic drug

Diagnosed with diabetes

Presence of anemia

Presence of cardiovascular disease Presence of musculoskeletal disease

Presence of asthma / chronic obstructive pulmonary disease

Presence of malignancy

Prsence of genital or gynecological disease (excluding menopausal symptoms)

Presence of neurological or psychiatric disease

Conditions involving acute or chronic inflammation

Experiencing acute or chronic infection

Displaying abnormal liver, kidney, or thyroid function tests

Engaging in smoking, alcohol consumption, or drug use

Suffering from sexual dysfunction (except for menopause-related reasons)

Unable to complete the study, or not attending 3-month or 6-month follow-up

Primary outcomes:
measure: The primary outcome measures were to assess the differences in MRS scores (somatic, psychological, urogenital and total score) and lipid profile (total cholesterol, LDL-C, HDL-C and triglyceride levels).
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istanbul Medipol University
state: Pendik /Istanbul
Study officials:
References:
citation: Shakeri F, Taavoni S, Goushegir A, Haghani H. Effectiveness of red clover in alleviating menopausal symptoms: a 12-week randomized, controlled trial. Climacteric. 2015;18(4):568-73. doi: 10.3109/13697137.2014.999660. Epub 2015 Feb 24.
citation: Kanadys W, Baranska A, Blaszczuk A, Polz-Dacewicz M, Drop B, Kanecki K, Malm M. Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2021 Apr 11;13(4):1258. doi: 10.3390/nu13041258.
citation: Luis A, Domingues F, Pereira L. Effects of red clover on perimenopausal and postmenopausal women's blood lipid profile: A meta-analysis. Climacteric. 2018 Oct;21(5):446-453. doi: 10.1080/13697137.2018.1501673.
citation: Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel G. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol. 2005 Nov;21(5):257-64. doi: 10.1080/09513590500361192.
citation: Campbell MJ, Woodside JV, Honour JW, Morton MS, Leathem AJ. Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study. Eur J Clin Nutr. 2004 Jan;58(1):173-9. doi: 10.1038/sj.ejcn.1601764.