The Effects of Systemic Isotretinoin Treatment on Adrenal Steroid and Sex Hormones Level in Severe Acne Vulgaris

Acne vulgaris is a chronic inflammatory skin disease involving the pilosebaceous unit, affecting approximately 95% of adolescents and young adults.

Follicular hyperkeratinization, increased sebum production, androgen hormones and inflammation play a role in the pathogenesis of acne. Androgens (Testosterone, DHEA-S and DHT) play a role in the development of acne, hypertrophy of the sebaceous glands and increased sebum production. Androgen receptors are located in the basal layer of the sebaceous glands keratinocytes and they are located in the outer sheath of the hair follicle. These receptors are responsible for the proliferative action of keratinocytes.

The relationship between androgen hormones and acne in women and prepubertal children is well known. Many studies have shown a strong association between acne and hyperandrogenism in women.

Systemic isotretinoin therapy can be used in patients with severe acne vulgaris who do not respond to topical and oral antibiotic treatments.

In recent studies, it has been shown that systemic isotretinoin used in acne treatment changes many hormones such as GnRH, FSH, LH, Estrogen, Progesterone, Testosterone, TSH, T4 and Prolactin and causes side effects such as menstrual irregularity and hirsutism.

However, data on the effect of oral isotretinoin on adrenal and sex hormones are contradictory.

In this study, it was aimed to evaluate the effect of oral isotretinoin on adrenal steroid and sex hormone levels and to compare it with a healthy control.

Isotretinoin treatment is started in acne vulgaris patients at a dose of 0.5-0.8mg/kg/day. The total cumulative dose is 120 mg/kg.

At baseline and at the 3rd month of isotretinoin treatment, 17-OH Progesterone, DHEA, DHEAS, Androstenedione, Aldosterone, Testosterone, Dihydrotestosterone, Estradiol, 17-OH Pregnenolone, Androsterone, Cortisol, Corticosterone, 11-Degesterone, 21, -Deoxycortisol, Pregnenolone, 11-Deoxycorticostreone hormones will be evaluated with LCMS/MS technique.

In addition, the FSH, LH, Prolactin, Estrogen, Testosterone, free testosterone, DHEA-s, SHBG, TSH, T4 hormone levels of the patients will be evaluated by ELISA method.

In the baseline 2nd, 3rd, 4th and 6th months of the treatment and 3 months after the treatment, the patients' height, weight, body mass index measurements, VAS scoring of patient treatment satisfaction, Global Acne Severity Score, Acne Quality of Life Score, and Modified Ferriman Gallwey Score for hirsutism will be recorded.

The side effects of isotretinoin such as menstrual irregularity, increased hair growth, and cheilitis, dryness of the oral mucosa, skin dryness, dermatitis seen in patients during treatment will be recorded.

*Hormone tests were performed on 2th and 3rd days of menstruation

Study Overview

• Status: Recruiting
• Conditions: Acne Vulgaris
• Intervention / Treatment: Diagnostic test: Hormone; Drug: Isotretinoin

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Baha Zaben, DR; Phone Number: +905459112899; Email: zabenbaha@gmail.com
• Study Contact Backup: Name: Ayse Deniz Yucelten, Prof

Study Locations

• Turkey
  • Istanbul, Turkey
    • Recruiting
    • Marmara University School of Medicine,Department of Dermatology.
    • Contact: Baha Zaben, DR; Email: zabenbaha@gmail.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients who applied to the Dermatology Outpatient Clinic with the diagnosis of severe acne vulgaris and will receive systemic isotrethionine treatment will be evaluated according to the inclusion/exclusion criteria.

Description

Inclusion Criteria:

• Severe to moderate acne vulgaris
• 14 - 20 Years old
• Female patients

Exclusion Criteria:

• Male patients
• Patients who received vitamin A or hormone therapy in the last 3 months
• Those with adrenal, thyroid, pituitary gland disease
• Those with psychiatric disorders
• History of drug use that causes acneiform eruption (eg, corticosteroids…)
• Acne conglobata and acne fulminans

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe acne vulgaris; 40 female patients aged 14-20 years, who were diagnosed with severe to moderate acne bulgaris and will be treated with isotretinoin.	Diagnostic test: Hormone; At baseline 17-OH Progesterone, DHEA, DHEAS, Androstenedione, Aldosterone, Testosterone, Dihydrotestosterone, Estradiol, 17-OH Pregnenolone, Androsterone, Cortisol, Corticosterone, 11-Degesterone, 21, -Deoxycortisol, Pregnenolone, 11-Deoxycorticostreone hormones will be evaluated.In addition, the FSH, LH, Prolactin, Estrogen, Testosterone, free testosterone, DHEA-s, SHBG, TSH, T4 hormone levels of the patients will be evaluated from all patients; Drug: Isotretinoin; İn the 3rd month of isotretinoin treatment, 17-OH Progesterone, DHEA, DHEAS, Androstenedione, Aldosterone, Testosterone, Dihydrotestosterone, Estradiol, 17-OH Pregnenolone, Androsterone, Cortisol, Corticosterone, 11-Degesterone, 21, -Deoxycortisol, Pregnenolone, 11-Deoxycorticostreone hormones will be evaluated.In addition, the FSH, LH, Prolactin, Estrogen, Testosterone, free testosterone, DHEA-s, SHBG, TSH, T4 hormone levels of the patients will be evaluated by ELISA method
Healthy control; 40 female patients aged 14-20 years	Diagnostic test: Hormone; At baseline 17-OH Progesterone, DHEA, DHEAS, Androstenedione, Aldosterone, Testosterone, Dihydrotestosterone, Estradiol, 17-OH Pregnenolone, Androsterone, Cortisol, Corticosterone, 11-Degesterone, 21, -Deoxycortisol, Pregnenolone, 11-Deoxycorticostreone hormones will be evaluated.In addition, the FSH, LH, Prolactin, Estrogen, Testosterone, free testosterone, DHEA-s, SHBG, TSH, T4 hormone levels of the patients will be evaluated from all patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FSH Level	Evaluation FSH levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
FSH Level	Evaluation FSH levels in after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
LH Level	Evaluation LH levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
LH Level	Evaluation LH levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Prolactin Level	Evaluation Prolactin levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Prolactin Level	Evaluation Prolactin levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Estrogen Level	Evaluation Estrogen levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Estrogen Level	Evaluation Estrogen levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Testosterone Level	Evaluation Testosterone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Testosterone Level	Evaluation Testosterone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Free-Testosterone Level	Evaluation Free-Testosterone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Free-Testosterone Level	Evaluation Free-Testosterone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
DHEA-s Level	Evaluation DHEA-s levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
DHEA-s Level	Evaluation DHEA-s levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
SHBG Level	Evaluation SHBG levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
SHBG Level	Evaluation SHBG levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
TSH Level	Evaluation TSH levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
TSH Level	Evaluation TSH levels iafter 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
T4 Level	Evaluation T4 levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
T4 Level	Evaluation T4 levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
17-OH Progesteroone Level	Evaluation 17-OH Progesteroone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
17-OH Progesteroone Level	Evaluation 17-OH Progesteroone after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
DHEA(LCMS) Level	Evaluation DHEA(LCMS) levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
DHEA(LCMS) Level	Evaluation DHEA(LCMS) levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
DHEA-S(LCMS) Level	Evaluation DHEAS(LCMS) levels in Severe Acne Vulgaris patient Before isotretinoin treatmen	Baseline (Before isotretinoin treatment)
DHEA-S(LCMS) Level	Evaluation DHEAS(LCMS) levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Androstenedione Level	Evaluation Androstenedione levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Androstenedione Level	Evaluation Androstenedione levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Aldosterone Level	Evaluation Aldosterone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Aldosterone Level	Evaluation Aldosterone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Testosterone(LCMS) Level	Evaluation Testosterone(LCMS) levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Testosterone(LCMS) Level	Evaluation Testosterone(LCMS) levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Dihydrotestosterone Level	Evaluation Dihydrotestosterone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Dihydrotestosterone Level	Evaluation Dihydrotestosterone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Estradiol Level	Evaluation Estradiol levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Estradiol Level	Evaluation Estradiol levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
17-OH Pregnenolone Level	Evaluation 17-OH Pregnenolone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
17-OH Pregnenolone Level	Evaluation 17-OH Pregnenolone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Androsterone Level	Evaluation Androsterone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Androsterone Level	Evaluation Androsterone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Cortisol Level	Evaluation Cortisol levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Cortisol Level	Evaluation Cortisol levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Corticosterone Level	Evaluation Corticosterone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Corticosterone Level	Evaluation Corticosterone after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
11-Deoxycortisol Level	Evaluation 11-Deoxycortisol levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
11-Deoxycortisol Level	Evaluation 11-Deoxycortisol levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Progesterone(LCMS) Level	Evaluation Progesterone(LCMS) levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
Progesterone(LCMS) Level	Evaluation Progesterone(LCMS) levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
21-Deoxycortisololone Level	Evaluation 21-Deoxycortisololone levels in Severe Acne Vulgaris patient Before isotretinoin treatment	Baseline (Before isotretinoin treatment)
21-Deoxycortisololone Level	Evaluation 21-Deoxycortisololone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
11-Deoxycortisolone Level	Evaluation 11-Deoxycortisolone levels in Severe Acne Vulgaris patient Before isotretinoin treatmen	Baseline (Before isotretinoin treatment)
11-Deoxycortisolone Level	Evaluation 11-Deoxycortisolone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment
Pregnenolone Level	Evaluation Pregnenolone levels in Severe Acne Vulgaris patient Before isotretinoin treatmen	Baseline (Before isotretinoin treatment)
Pregnenolone Level	Evaluation Pregnenolone levels after 3 month of isotretinoin treatment	3rd month of isotretinoin treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of hormone levels in acne vulgaris patients and healthy group	Comparison of all hormone levels in acne vulgaris patients and healthy group	Baseline
Menstrual İrregularity	Evaluation of side effects such as menstrual irregularity that can be seen due to isotretinoin	2. 4. 6. months and 3 month after treatment
Relationship between Menstrual irregularity and hormone levels	Evaluation of the relationship between menstrual irregularity and changes in hormone levels	3rd month of isotretinoin treatment

Collaborators and Investigators

• Sponsor: Marmara University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Estimated): June 30, 2023
• Study Completion (Estimated): June 30, 2023

Study Registration Dates

• First Submitted: March 26, 2023
• First Submitted That Met QC Criteria: June 11, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 11, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Sex hormones; Isotretinoin; Adrenal steroid hormones
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Hormones; Isotretinoin
• Other Study ID Numbers: 09.2022.464

Drug and device information, study documents

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