The impact of isotretinoin on the pituitary-ovarian axis: An interpretative review of the literature

Abdelhamed, Amr; El-Dawla, Reham Ezz; Karadağ, Ayşe Serap; Agamia, Naglaa; Melnik, Bodo C.

doi:10.1016/j.reprotox.2021.06.017

Cited by 12 publications

(9 citation statements)

References 121 publications

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“…Many studies reported that 13-RA causes disruption in lipids such as dyslipidemia, hypertriglyceridemia [70], and imbalance in endocrine systems [81]. This study proves that free fatty acids are reduced due to depression and stress.…”

Section: Discussionsupporting

confidence: 65%

13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

Al-Saeedi

Rajendran

2023

Mol Imaging

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Purpose. Study the effects of 13-cis-retinoic acid (13-RA), a synthetic analogue of a vitamin A used for the treatment of severe acne, on the blood flow in the rat brain using technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) imaging. Methods. A total of 30 adult male Wistar rats were divided into the control (C), low-dose (L), and high-dose (H) groups. The L and H rats were exposed subcutaneously to 0.3 and 0.5 mg, respectively, of 13-RA per kg of body weight for seven days. Brain blood flow imaging was performed using a gamma camera. Then, a region of interest (ROI) around the brain (target, T), a whole-body region (WB), and a background region (BG) was selected and delimited. The net 99mTc-HMPAO brain counts were calculated as the net target counts, NTC = T − BG / WB − BG in all groups. At the end of the 99mTc-HMPAO brain blood flow imaging, the brain, heart, kidney, lung, and liver were rapidly removed, and their uptake was determined. Brain histopathological analysis was performed using hematoxylin and eosin stains. In addition, the plasma fatty acids were studied using gas chromatography/mass spectrometry. Results. There were highly significant differences between L and H in comparison to C and across the groups. The 99mTc-HMPAO radioactivity in the brain showed increased uptake in a dose-dependent manner. There were also significant changes in the brain tissues and decreased free fatty acids among the groups compared to C. Conclusion. 13-RA increases 99mTcHMPAO brain perfusion, uptake, and function and reduces fatty acids.

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Section: Discussionsupporting

confidence: 65%

13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

Al-Saeedi

Rajendran

2023

Mol Imaging

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“…ISO has adverse effects on the pituitary-ovarian axis, which can enhance granulosa cell apoptosis and reduce follicular reserve. 22 In the study conducted by Schaefer et al, 23 ISO was considered the most teratogenic drug after thalidomide. Even a simple capsule may cause congenital malformations within the first trimester.…”

Section: Resultsmentioning

confidence: 99%

Physiological and Psychological Effects of Isotretinoin in the Treatment of Patients with Acne: A Narrative Review

Ding¹,

Zheng²,

Jin³

2023

CCID

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Isotretinoin (ISO) is a powerful vitamin A derivative that offers the potential for treatment of permanent remission of acne; however, its potential side effects on both physiological and psychological aspects limit its application. This article reviews the side effects of ISO from physiological and psychological aspects in detail, to better screen the suitable population of ISO and improve the efficiency of clinical treatment. Our findings indicate that ISO may cause teratogenicity, skin reactions, ocular reactions, changes in blood indicators, and occasional acne fulminans. To optimize clinical treatment, more attention should be paid to identifying the specific conditions under which these reactions occur, how severe they are, and how they subside to alleviate patient concerns. Regarding the controversial issue of psychological side effects caused by ISO, researchers should shift their focus to the psychological problems that acne itself may cause.

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“…There is compelling translational evidence that isotretinoin-mediated upregulation of p53 expression explains isotretinoin’s teratogenicity via p53-mediated neural crest cell apoptosis [ 41 , 42 ]. Isotretinoin also induces apoptosis in primary human keratinocytes [ 56 ], melanoma cells [ 58 , 59 ], rat ovarian granulosa cells [ 87 , 88 ], hepatoma cells [ 89 ], associated with decreased expression of the apoptosis inhibitor survivin [ 89 ]. Increased serum levels of survivin have been reported in acne patients compared to controls [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris

et al. 2022

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The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy.

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The impact of isotretinoin on the pituitary-ovarian axis: An interpretative review of the literature

Cited by 12 publications

References 121 publications

13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

13-cis-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

Physiological and Psychological Effects of Isotretinoin in the Treatment of Patients with Acne: A Narrative Review

Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris

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