Comparison of Substances in Combined Oral Contraceptives Used in Acne Vulgaris, Hirsutism, Migraine, and Dysmenorrhea.

Combined oral contraceptives (COC) are widely used not only for contraception, but also a therapeutic option in conditions such as acne vulgaris, hirsutism, migraine, and dysmenorrhea. Their effectiveness results from the effect of estrogen and progestogen components on androgen synthesis and ovulation, which can lead to symptom relief in these disorders. However, the benefits of COC must be weighed against the risk of adverse effects, including thromboembolic complications, particularly in women with additional risk factors [ 1 , 2 ]. The optimal choice of hormonal preparation and dosing regimen remains a matter of debate, especially considering the need for individualized therapy according to patient characteristics and comorbidities. This review aims to summarize current evidence on the efficacy and safety of different COC formulations in the treatment of acne vulgaris, hirsutism, migraine, and dysmenorrhea, with particular emphasis on the clinical context and the need for personalized management [ 3 ]. This narrative review assessed and compared various theoretical approaches. Studies showing the advantages and disadvantages of specific oral contraceptive substances are presented, then examples are given of patients for whom they would be the best choice. This review aimed to answer in the following questions: Is there is an ideal combined contraceptive pill that can be prescribed to every patient? Which combined contraceptive pill is best in a particular patient? In which conditions are COCs therapeutic? What are the limitations of the substances concerned, including potential adverse effects? A comprehensive search was performed in 3 major scientific databases: PubMed, Google Scholar, and Scopus, covering publications up to March 2025. The search strategy was based on the following predefined keywords: Oral contraceptive, Combined oral contraceptive, Acne vulgaris, Hirsutism, Migraine, and Dysmenorrhea. To enhance the completeness of the review, the reference lists of selected articles were also manually screened for additional relevant studies. The article inclusion criteria were: original research articles; systematic reviews and meta-analyses; case reports addressing rare or novel aspects of COC therapy; studies focusing on the use of COCs in the treatment of acne vulgaris, hirsutism, migraine, or dysmenorrhea; and publications available in full text and written in English. We excluded articles not published in English, conference abstracts, letters to the editor, publications without available full text, narrative reviews, studies not directly related to COC use in the specified clinical conditions, publications with insufficient methodological quality, or lacking relevant clinical outcomes for this review. Each included study was assessed for methodological rigor (eg, randomization method, sample size, length of follow-up), clinical relevance, and compliance with the inclusion criteria. Extracted data included: characteristics of the study population (eg, age, comorbidities such as PCOS), type and dosing regimen of the oral contraceptive used, primary clinical outcomes (eg, reduction of acne lesions, frequency or intensity of migraine, severity of dysmenorrhea), and safety profile (eg, adverse effects, thromboembolic events). The strategy of studies qualification for this paper is visualized in the flowchart in Figure 1 . The results were organized thematically by condition and analyzed comparatively, focusing on treatment efficacy and tolerability. Individual factors potentially influencing treatment response (eg, BMI, ethnicity, hormonal status) were also considered. Identified limitations of the available literature (eg, small sample sizes, lack of direct comparisons, short follow-up durations) were noted and discussed. A total of 24 articles met the inclusion criteria and were included in this review. For clarity and better visualization, the studies were categorized into 4 thematic groups based on the clinical indication addressed: acne vulgaris, hirsutism, migraine disorders, and dysmenorrhea.

Primary dysmenorrhea is defined in the literature as menstrual pain without pelvic pathology. According to available sources, it affects 50% to 90% of adolescent girls and women of childbearing age [ 6 ]. Primary dysmenorrhea typically begins during the first menstruation or within 6 to 12 months thereafter, as it occurs only during ovulatory cycles. This pain is described as sharp and predictable, lasting up to 72 hours, with the most intense phase occurring on the first or second day of the cycle. The area of pain can extend beyond the lower abdomen to the lower back and thighs [ 17 ]. At the core of this issue is the excessive production of endogenous prostaglandins by the endometrium, resulting in uterine muscle ischemia due to increased contractility, and consequent pain. COCs inhibit ovulation, thereby reducing prostaglandin synthesis (PG), suggesting that they can help alleviate painful menstrual symptoms [ 18 ]. We found 4 articles evaluating effectiveness of COC in the treatment of dysmenorrhea ( Table 4 ). A 2020 Japanese study of 186 patients showed that EE/DRSP therapy in a 24/4 regimen significantly improves quality of life in terms of pain reduction and social, mental, and physical functioning. Moreover, after therapy, quality of life was better that in the general population [ 19 ]. Strowitzki et al compared the classic regimen (28 days) with flexible, extended (24–120 days of continuous use) EE/DRSP in women with moderate to severe primary dysmenorrhea. The extended regimen was more effective in reducing the number of days with pain and the intensity of symptoms, while maintaining an acceptable safety profile [ 20 ]. A smaller study of 5 women showed that EE 50 μg therapy with lynestrenol 1 mg/day reduces uterine muscle tension as assessed by hysteroscopy and leads to a significant reduction in pain, including complete resolution of symptoms in some patients [ 21 ]. A 2023 systematic review of 21 RCTs by Schroll et al found that COCs are more effective than placebo in relieving painful menstruation, although there is no clear evidence of their superiority over non-steroidal anti-inflammatory drugs (NSAIDs). The effectiveness of treatment should be weighed against the risk of adverse effects such as irregular bleeding, headaches, and nausea [ 22 ]. COCs, especially EE/DRSP-based regimens, are effective in reducing menstrual pain and improving quality of life. Extended regimens may offer additional benefits in reducing the number of days with pain. Nevertheless, the lack of a clear advantage over NSAIDs suggests that the choice of therapy should be individualized according to patient preference, symptom severity, and safety profile.

Our review of the literature raises the questions of whether there is there an ideal COC that could be prescribed to all patients, and is it worthwhile to include hormonal treatment at all, when COCs are so controversial and their potential adverse effects are feared. The differences between preparations are due to the properties of the progestogens, including anti-androgenic potency and safety profile. CMA, DNG, and DRSP have the strongest anti-androgenic effect and produce the best results [ 2 , 7 ]. DSG is more effective than LNG, but its anti-androgenic effect is moderate [ 5 ]. LNG is the progestogen with the lowest anti-androgenic potential of those listed – it is still effective, but is less effective in the treatment of acne than the newer substances [ 8 ]. DRSP additionally lowers free testosterone concentrations, resulting in better control of hyperandrogenic symptoms. The cited clinical studies and systematic reviews confirm the superiority of modern progestogens (CMA, DNG, DRSP) over older ones (LNG) in the treatment of acne and hirsutism in women using COCs. Studies indicate that progestogens with varying androgenic activity, such as LNG, can increase the risk of cardiovascular complications, which is particularly important in women with a predisposition to migraine or a history of thrombosis [ 23 ]. DRSP works well in patients with migraine without aura. COCs with oestrogen are contraindicated in women with migraine with aura due to the risk of vascular complications and the possibility of migraine exacerbation [ 13 ]. EE used in monotherapy results in a 3-fold increased risk of cryptogenic stroke [ 14 ]. This raises other questions: how can we monitor patients with migraine using COC to minimise the risk of complications? Does COC alter brain neurochemistry in a reversible way? Pills with DRSP are preferred for the treatment of primary dysmenorrhea due to their strong analgesic effect, good metabolic profile, and additional benefits, such as improved quality of life. Flexible and 24/4 regimens can reduce the number of days with pain more effectively than the classic 28-day regimens [ 18 – 20 ]. There are still many important knowledge gaps regarding the use of oral hormonal contraception to treat conditions such as acne, hirsutism, migraine, and painful menstruation. Comprehensive studies analysing how individual factors such as BMI, ethnicity, the presence of PCOS or genetic predisposition affect the efficacy and safety of therapy are lacking. It is known, for example, that women with a BMI below 20 kg/m 2 respond better to acne treatment, but the mechanisms behind this phenomenon remain unclear. New generations of progestogens, such as the combination of estetrol and drospirenone, require further comparative studies of cardiovascular safety and efficacy in treating symptoms of androgenization [ 24 ]. Another gap is the lack of data on the long-term effects of continuous regimens (28/0), which could theoretically minimize estrogen withdrawal-related symptoms such as migraines or painful menstruation, but their efficacy and safety need to be determined in clinical trials. Direct comparisons of different dosing regimens (21/7, 24/4, 28/0) in terms of efficacy in the treatment of menstrual migraines, impact on thrombosis risk, and patient acceptance are also needed [ 13 ]. Additionally, a Japanese study showed that the use of EE/DRSP on a 24/4 cycle improves wellbeing and reduces pain, suggesting that this treatment regimen may be more beneficial than other available options for the treatment of dysmenorrhea [ 18 ]. There are still insufficient data on the safety of COCs in women with migraine with aura or a history of thrombosis, as well as on the interaction of COCs with antiepileptic, antidepressant, and antiretroviral drugs. There is also a lack of imaging studies (MRI/fMRI) assessing the long-term effects of COCs on brain structure and function, such as grey matter changes, neuronal connectivity patterns, or stress responses, considering the patient’s age at therapy initiation, genetics, and duration of use. In addition, less than half of women using COCs receive information about therapeutic benefits beyond contraception (eg, in treatment of endometriosis), indicating the need to develop more effective educational strategies tailored to different ethnic and socio-economic groups. Finally, innovative hormone delivery systems, such as intrauterine systems with UPA or transdermal combination systems, require further research on efficacy, bioavailability, and stability of hormone concentrations. All these gaps point to the need for multidisciplinary research with large groups of patients, using advanced molecular and imaging techniques, to enable optimisation and personalization of hormone therapy. The choice of an appropriate COC should always be individually tailored to a woman’s health needs, not only to prevent pregnancy, but also to treat conditions such as acne, hirsutism, menstrual migraine, and painful periods. Hormonal preparations vary in their efficacy and safety profile depending on the clinical problem and patient characteristics (eg, BMI, PCOS, risk of thrombosis). The optimal treatment can significantly improve quality of life, but requires an informed choice and consideration of individual contraindications and risk of adverse effects. There is no single ‘perfect’ COC for everyone. The choice of hormonal contraception should be based on medical indications and patient safety. COCs can be effective in relieving the symptoms of acne, hirsutism, menstrual migraine, and painful menstruation, but require an individualized approach and monitoring.