Effects of High Intensity Statin Therapy on Steroid Hormones and Vitamin D in Type 2 Diabetic Men

The aim of the study was to assess the effect of high intensity statin therapy on testicular and adrenal steroids and vitamin D levels in type 2 diabetes males.It is a prospective study, conducted between march 2021 and July 2022, including 60 men with type 2 diabetes, aged 40 - 65 years, statin-free, and in whom a treatment with high intensity statin was indicated. The patients had two visits, before and six months after a daily intake of 40 mg of atorvastatin. During each visit, they underwent a clinical examination including the Androgen Deficiency in the Aging Male (ADAM) questionnaire and a fasting blood sample was collected for biological and hormonal measurements.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Vitamin D Deficiency; Adrenal Insufficiency; Hypogonadism, Male; Statin Adverse Reaction; Dyslipidemia Associated With Type II Diabetes Mellitus
• Intervention / Treatment: Drug: Atorvastatin 40 Mg Oral Tablet

Detailed Description

Study design and setting It is a prospective study carried out at the department of Endocrinology of the University Hospital La Rabta, Tunis, between March 2021 and July 2022. The protocol was approved by La Rabta University Hospital local ethics committee.

Subjects Inclusion criteria were male subjects, aged between 40 and 65 years, with T2D, naive to statin and in whom a high intensity statin therapy was indicated according to the recommendations of the American Diabetes Association 2021 i.e in secondary cardio-vascular prevention or in primary prevention if the patient was aged more than 50 years or if other atherosclerotic cardiovascular disease risk factors were associated.

All patients gave an informed written consent to participate in the study. Exclusion criteria were the use within the last six months of drugs interfering with steroidogenesis (androgens, anti-androgens, Gn-RH analogues, corticosteroids, antiepileptics, barbiturates or other enzyme inducer or inhibitor); history of endocrinopathy (hypogonadism, testicular tumor, pituitary insufficiency, adrenal insufficiency, uncontrolled hypothyroidism); history of severe systemic disease (hepatic insufficiency, cirrhosis, alcoholism, severe or moderate renal insufficiency, symptomatic heart failure, chronic inflammatory disease); myocardial infarction or stroke within the last six months; statin intolerance; withdrawal of consent; loss to follow-up; poor compliance with treatment.

The number of subjects required for the study was calculated. When considering alpha= 0.05, beta= 0.10, and a magnitude of difference in testosterone levels of 0.59 ng/ml according to Dobs AS et al. study with an estimated common standard deviation of 1.0, the number of subjects required is estimated to be 50.

Protocol and data collection Visit 1: inclusion visit. The subjects were included and signed an informed consent to participate in the study. Visits 1 and 2 were performed on the same day in fasting patients.

Visit 2:

Clinical data were determined: age; habits; history; ongoing treatment; signs of adrenal insufficiency (weight loss, anorexia, asthenia, dizziness on standing, signs of hypoglycemia); signs of hypogonadism (decreased libido, presence or absence of nocturnal erections); number of sexual intercourses per month. Patients responded to the androgen deficiency in the aging male questionnaire (ADAM) translated to Tunisian dialect by four physicians from the same department.

Patients underwent a physical examination: measure of weight, height, and lying and standing blood pressure, presence of melanoderma, gynecomastia or myalgia.

A blood sample was collected between 8 a.m. and 9 a.m., after 12 hours of fasting, for the measurement of glucose, HbA1c, total cholesterol, triglycerides, high density lipoprotein cholesterol (HDLc), creatinine, sodium, potassium, transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), creatine phosphokinase (CPK), calcium, phosphate, albumin, total testosterone, sex hormone binding globulin (SHBG), estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol, DHEAS (dehydroepiandrosterone sulfate), parathormone (PTH), and 25-hydroxy vitamin D. Blood samples were frozen at -20°c at the laboratory until hormonal measurements.

Treatment with 40 mg atorvastatin a day was initiated in all patients.

Visit 3: after six months of treatment:

The clinical and paraclinical parameters determined at visit 1 were determined again. The dose and the compliance of statin intake were evaluated by Girerd questionnaire. The occurrence of clinical adverse events of statin such as myalgia, arthralgia, digestive symptoms was recorded.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tunisia
  • Tunis, Tunisia
    • University Hospital La Rabta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• male subjects
• aged between 40 and 65 years
• Type 2 diabetes
• naive to statin
• patients in whom a high intensity statin therapy was indicated according to the recommendations of the American Diabetes Association 2021 i.e in secondary cardio-vascular prevention or in primary prevention if the patient was aged more than 50 years or if other atherosclerotic cardiovascular disease risk factors were associated.

Exclusion Criteria:

• the use within the last six months of drugs interfering with steroidogenesis (androgens, anti-androgens, Gn-RH analogues, corticosteroids, antiepileptics, barbiturates or other enzyme inducer or inhibitor)
• history of endocrinopathy (hypogonadism, testicular tumor, pituitary insufficiency, adrenal insufficiency, uncontrolled hypothyroidism)
• history of severe systemic disease (hepatic insufficiency, cirrhosis, alcoholism, severe or moderate renal insufficiency, symptomatic heart failure, chronic inflammatory disease)
• myocardial infarction or stroke within the last six months
• statin intolerance
• withdrawal of consent
• loss to follow-up
• poor compliance with treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: type 2 diabetic patients at high cardio vascular risk; atorvastatin 40 mg a day for six months	Drug: Atorvastatin 40 Mg Oral Tablet; daily drug intake during six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in testosterone level after atorvastatin treatment	decrease in testosterone level	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in cortisol level after atorvastatin treatment	decrease in cortisol	six months
change in DHEAS levels after atorvastatin treatment	decrease in DHEAS	six months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in vitamin D level after atorvastatin treatment	decrease in vitamin D	six months

Collaborators and Investigators

• Sponsor: Hopital La Rabta
• Investigators: Principal Investigator: Melika Chihaoui, Professor, La Rabta Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): July 30, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: type 2 diabetes; vitamin D; cortisol; testosterone; DHEAS; statin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Lipid Metabolism Disorders; Adrenal Gland Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Vitamin D Deficiency; Dyslipidemias; Hypogonadism; Adrenal Insufficiency; Eunuchism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: HLaRabta22021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: after the publication
• IPD Sharing Access Criteria: on request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No