Comparative evaluation of the effectiveness and safety of acne treatment with systemic isotretinoin in monotherapy and together with combined oral contraceptives in women

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Introduction

The name of dermatosis "acne" has ceased to be used with the definition of "youthful" for a long time, because this disease can proceed or even occur after pubertal age. Moreover, it is mainly observed among women [1; 2]. E.R. Araviyskaya marks that about 20 % of adult women are concerned about the appearance of acne on the chin before menstruation [3]. Systemic isotretinoin, hormonal therapy, antibacterial agents, and azelaic acid are used externally to treat acne among women [4]. Antibacterial therapy suppresses the activity of C. acnes and has a remarkable anti-inflammatory effect [5]. Azelaic acid has primarily anticomedogenic and keratolytic effects [6]. Combined oral contraceptives are predominantly used among hormonal preparations [7]. These combined oral contraceptives reduce absolute and relative hyperandrogenemia, contributing to the reduction of sebum production, which is a key factor in the progression of acne [8]. Systemic isotretinoin affects all components of acne pathogenesis: it inhibits the function of sebaceous glands, eliminates follicular hyperkeratosis and has antibacterial and anti-inflammatory effects [9]. It is important to remember that systemic isotretinoin is teratogenic, therefore, women should avoid pregnancy during treatment and for one month after its termination [10]. Many people use combined oral contraceptives for this purpose, the effect of which was mentioned above [11].

The aim of the study is to provide a comparative evaluation of the efficiency and safety of acne treatment among women with systemic isotretinoin in monotherapy and in combination with combined oral contraceptives.

Materials and methods

The retrospective study was conducted on the basis of the inpatient department of the regional skin and venereological dispensary of the Perm region and medical centers A2Med and „Genesis“. Sixty-five women with serious papulopustular acne in the age range of 20–35 years participated in the study. There were distinguished two groups. The first group consisted of 35 women using systemic isotretinoin of 0.5 mg/kg per day in monotherapy for acne treatment; the second group consisted of 30 women using systemic isotretinoin of 0.5 mg/kg per day in combination with combined oral contraceptives. The groups were comparable in social and somatic status, body weight and height, all were residents of the Perm region, and all gave voluntary informed consent to participate in the study. The exclusion criteria were serious endocrine pathology, gynecological diseases in anamnesis, cardiovascular diseases, liver and kidney pathology, smoking, alcoholism, use of external medications for acne treatment.

A comprehensive clinical and laboratory examination was conducted. There were studied the complaints and made anamnesis of the disease and life, assessed the general condition of the body, examination of skin and mucous membranes, general blood and urine tests, biochemical blood analysis with determination of lipid spectrum, hepatic transaminases, hormonal homeostasis. The results were analyzed using the methods of parametric and nonparametric statistics using Microsoft Excel and Statistica 5.1 for Windows (Stat Inc., USA). The standard error (m) was used in the calculations, and the level of statistical significance was noted at p < 0.05.

Results and discussion

Most women with serious papulopustular acne, who receive systemic isotretinoin in monotherapy, have improvement after 4 weeks and complete clinical recovery after 24 weeks from the beginning of therapy. Most improvement occurs after 2 weeks and complete clinical recovery occurs after 16 weeks of treatment among women with serious papulopustular acne, who receive systemic isotretinoin in combination with combined oral contraceptives (Table 1).

 

Table 1. Specific features of the progression of the primary effect of systemic isotretinoin in combination with monotherapy and combined oral contraceptives (% ± m)

Primary clinical effect	Group I, n = 35	Group II, n = 30	p
Occurrence of improvement after 2 weeks	22.9 ± 7.1*	73.3 ± 8.1	0.004
Occurrence of improvement after one month	77.1 ± 7.1*	26.7 ± 8.1	0.004
Complete clinical recovery after 16 weeks	14.3 ± 5.9*	80.0 ± 7.3	0.001
Complete clinical recovery after 24 weeks	85.7 ± 5.9*	20.0 ± 7.3	0.001

Note: there were statistically significant differences with the group of women with serious papulopustular acne receiving systemic isotretinoin in combination with combined oral contraceptives, *p < 0.05.

 

The most common side effects of systemic isotretinoin in the course of treatment of serious papulopustular acne among women were cheilitis, xerosis, retinoid dermatitis, and telogen alopecia. Cheilitis was observed among the vast majority of patients equally in both groups. Xerosis, retinoid dermatitis, and telogen alopecia were more frequently observed among women receiving systemic isotretinoin in monotherapy (Table 2).

 

Table 2. Specific features of side effects during monotherapy of systemic isotretinoin and in combination with oral contraceptives (% ± m)

Side effect	Group I, n = 35	Group II, n = 30	p
Cheilitis	91.4 ± 4.7	86.6 ± 6.2	0.537
Xerophthalmia and conjunctivitis	14.3 ± 5.9	10.0 ± 5.5	0.540
Nasal hemorrhage	11.4 ± 5.4	10.0 ± 5.5	0.853
Xerosis	60.0 ± 8.3*	26.7 ± 8.1	0.007
Retinoid dermatitis	45.7 ± 8.4*	16.7 ± 6.8	0.012
Telogen alopecia	42.8 ± 8.4*	13.3 ± 6.2	0.009
Paronychia and onychodystrophy	8.6 ± 4.7	6.7 ± 4.6	0.774
Headache, depression	5.7 ± 3.9	10.0 ± 5.5	0.518
Arthralgias and myalgias	5.7 ± 3.9	6.7 ± 4.6	0.873
Anemia	5.7 ± 3.9	6.7 ± 4.6	0.873
Hyperlipidemia	11.4 ± 5.4	10.0 ± 5.5	0.853
Increasing of liver transaminase level	8.6 ± 4.7	6.7 ± 4.6	0.774

Note: there were statistically significant differences with the group of women with serious papulopustular acne receiving systemic isotretinoin in combination with combined oral contraceptives, *p < 0.05.

 

Women with serious papulopustular acne who receive systemic isotretinoin in monotherapy have significantly higher progesterone level and lower estradiol value than women using systemic isotretinoin in combination with combined oral contraceptives (Table 3).

 

Table 3. Characteristics of hormonal homeostasis among women with acne during treatment using systemic isotretinoin in monotherapy and in combination with oral contraceptives (% ± m)

Indicators of hormonal homeostasis	Group I, n = 35	Group II, n = 30	p
Absolute hyperandrogenemia	17.1 ± 6.4	6.7 ± 4.5	0.366
Hyperprogesteronemia	62.9 ± 8.2*	10.0 ± 5.5	0.001
Decreasing estradiol level in the blood	34.3 ± 8.0*	6.7 ± 4.5	0.006

Note: there were statistically significant differences with the group of women with serious papulopustular acne receiving systemic isotretinoin in combination with combined oral contraceptives, *p < 0.05.

 

Combined oral contraceptives eliminate hyperandrogenemia, and this results in decreased production and normalization of sebum chemistry. In this process, follicular hyperkeratosis and inflammatory response of the pilosebaceous follicle are indirectly reduced. Thus, combined oral contraceptives enhance the primary effect of systemic isotretinoin. In addition, estrogens, which are part of combined oral contraceptives, have a softening and moisturizing effect on the skin, giving it elasticity and softness, which can smooth unwanted adverse reactions of systemic isotretinoin.

Conclusions

1. Systemic isotretinoin has shown high efficiency and safety in the process of treatment from acne among women.
2. Combined oral contraceptives normalize hormonal homeostasis, which helps to eliminate acne.
3. When systemic isotretinoin is used in combination with combined oral contraceptives, the primary clinical effect occurs earlier, and side effects are less frequent and less serious than with the use of systemic isotretinoin monotherapy.
4. The combined use of systemic isotretinoin and combined oral contraceptives is the optimal treatment for acne among women.

About the authors

V. D. Elkin

E.A. Vagner Perm State Medical University

Email: elkin.vladimir.d@gmail.com
ORCID iD: 0000-0003-4727-9531

MD, PhD, Professor, Head of the Department of Dermatovenerology

Russian Federation, Perm

M. Yu. Kobernik

E.A. Vagner Perm State Medical University

Author for correspondence.
Email: margo110875@yandex.ru
ORCID iD: 0000-0002-3549-0076

Candidate of Medical Sciences, Associate Professor of the Department of Dermatovenerology

Russian Federation, Perm

References

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