AFA is defined as acne that affects women >25-years. The condition may persist continuously or intermittently from adolescence, or manifest for the first time in women >25-years.  Acne negatively impacts the quality of life of patients – psychologically as well as socially.¹

The onset of acne is influenced by genetic predisposition, and androgenic hormone stimulation. The latter leads to an excessive increase in sebaceous secretion.³

Apart from sebaceous secretion, other pathological processes involved in the onset of acne include:²

• Cutaneous dysbiosis with selection of virulent subtypes of Cutibacterium acnes (C. acnes)and/or of other bacterial agents
• Abnormalities of differentiation and proliferation of keratinocytes of the pilosebaceous follicle
• Inflammation and activation of the innate immune response.

Severity of adult female acne

Clinical forms of AFA include:²

1. Inflammatory acne: Affects 80% of patients and is characterised by the pres­ence of superficial inflammatory lesions (papules, pustules) all over the face with few nodules.
2. Localised acne: Affects 20% and is predominantly found in the mandibular region, chin, and is characterised by many closed comedones and cysts with a few inflamma­tory lesions.

AFA becomes less common >30-years but may continue. Some women may even develop menopausal acne.²

Various scales have been developed to assess the severity of acne to ensure that patients receive the best treatment. These include for example the Global Evaluation Acne Scale and the Adult Female Acne Scoring Tool (AFAST).¹

Table 2: The Adult Female Acne Scoring tool¹

Adult female acne as an endocrinological disease

Other clinical signs indicative of endocrinological involvement in the onset of AFA include hirsutism(20% to 30%), polycystic ovary syndrome (17% to 27%, and in severe acne 51%), seborrhoea, alopecia, menstrual disorders, ovulatory dysfunction, infertility, early puberty, metabolic syndrome and virilisation.¹

The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society appointed an expert task force in 2022 to evaluate the link between hyperandrogenism and AFA, and to propose strategies to evaluate and treat this patient population.²

The expert task force found that increased androgen production plays a key role in inducing sebum alterations in adult acne. Serum androgen values (total testosterone, free testosterone, and dehydroepiandrosterone [DHEA]) should be measured in women living with adult acne.²

What treatments are recommended for women with acne and hyperandrogenism?

A stepwise approach to AFA treatment is recommended, including the use of different agents. The choice of agent should be based on the severity (see Table 1) and type of acne lesion. The recommended stepwise approach includes:²

Step 1: Topical agents for mild forms of acne.

Step 2: Topical agents plus an oral antibiotic or hormonal therapy for moderate forms of acne.

Step 3: Topical agents, oral antibiotics and hor­monal therapy, or an oral retinoid (isotretinoin) in severe forms of acne.

Hormone therapy is often prescribed for the treatment of female acne. Combined hormonal contraception consists of two components: Oestrogen and progestin. The oestrogen components are ethinyl oestradiol and oestradiol valerate.³

Combined contraceptives are available in oral and patch formulations as well as vaginal rings. Progestin-only contraception is available in oral and depot formulations, as well as intrauterine devices, and implants.³ 

Testosterone, DHEA, and dihydrotestosterone (DHT) stimulate sebaceous gland growth and sebum production, while oestrogens have the opposite effect - they inhibit the secretion of androgens, modulate genes involved in the growth of the sebaceous gland and inhibit their function. Thus, the activity of the sebaceous gland depends on the oestrogen/androgen ratio.¹

Combined oral contraceptives (COCs) are recommended for the treatment of acne, while progestin-only contraceptives may worsen the skin disease.^1,3 

According to the AE-PCOS expert task force, COCs should be added to topical or systemic treatment in AFA and proven hyperandrogenism, regardless of severity. All second- and third-generation COCs may be used, regardless of the oestrogen dose and progestin component.²

Spironolactone may be added to COCs in women living with moderate or severe hyperandrogenic adult acne who do not respond to usual treatments. COCs may also be used in non-hyperandrogenic patients with adult acne as second-line therapy.² 

Are COCs safe and effective to treat adult female acne?

Drospirenone 3mg/ethinyloestradiol 20μg is a low-dose COC that is often prescribed to treat AFA. Numerous studies have investigated the efficacy and safety of this combination.^4,5,6,7

Maloney et al (2008) compared the efficacy and safety of drospirenone/ethinyloestradiol (group 1) to treat moderate acne to placebo (group 2). Drospirenone/ethinyloestradiol was used in a 24/4 regimen for six months.  The primary outcomes were acne lesion counts and investigators’ assessment at months one, three, and six. Participants in group 1 (n=270) achieved a 46.3% reduction in lesions compared to 30.6% in group 2 (n=268). The odds of participants in group 1 having ‘clear’ or ‘almost clear’ skin was about three-fold greater than those in group 2. The safety profile of drospirenone/ethinyloestradiol was consistent with low-dose COCs.⁴

Maloney et al’s findings were confirmed in a later study by Koltun et al (2011). Koltun et al compared the efficacy of drospirenone/ethinyloestradiol (group 1)used in a 24/4 regimen for six months to placebo (group 2).  Primary outcome measures were mean percent change in acne lesion counts, and investigators' assessment of acne from baseline to endpoint. There were significantly greater reductions in the mean percent change from baseline to endpoint in inflammatory, non-inflammatory and total lesion counts in group 1 participants (n=451) compared to those in group 2 (n=442). The odds of participants in group 1 having 'clear' or 'almost clear' skin were around three-fold greater than those in group 2.⁵

A 2012 Cochrane review evaluated six COCs including drospirenone/ethinyloestradiol and found that COCs are effective in reducing inflammatory and non-inflammatory facial acne lesions. They found that drospirenone/ethinyloestradiol appeared to be more effective than norgestimate or nomegestrol acetate in the treatment of acne.⁶

Pali et al (2013) compared the safety and efficacy of drospirenone/ethinyloestradiol (group 1) to placebo (group 2) to treat truncal acne in women. Primary endpoints were improvement in non-inflammatory, inflammatory, and total truncal acne lesion counts from baseline to endpoint (24 weeks) and mean percent change. Participants in group 1 (n=15) had significant reductions in non-inflammatory (52.1%), inflammatory (53.2%) and total lesions (57.3%) compared to those in group 2 (n=10) (-9.2%, 18.2% and 17.0 %, respectively) by week 24. The percentage of participants in group 1 rated as treatment success were 53.3% and 60% based on Investigator Global Assessment and Subject Global Assessment, respectively. Treatment with drospirenone/ethinyloestradiol was well tolerated. The team concluded that drospirenone/ethinyloestradiol is a safe and significantly effective treatment for moderate truncal acne (10-50 lesions).⁷

Conclusion

Hormone therapy is a highly effective treatment for AFA - even in patients without serum hormone changes. They are suitable for long-term therapy because they have no potential to induce bacterial resistance and represent an alternative to systemic antibiotics.³

Hormone therapy is recommended for adult women who present with severe seborrhoea and endocrine changes, experience worsening of acne in the premenstrual period, and for those with persistent recalcitrant inflammatory acne when standard treatments (eg repeated cycles of isotretinoin) have failed, or when COCs are required or requested.³

Hormone therapy reduces excess sebum production, and it is therefore recommended that they are used in combination with agents (eg antibiotics, benzoyl peroxide, retinoids, and azelaic acid) that act on other pathogenic factors.³

References

1. Bagatin E, Freitas THP, Rivitti-Machado MC, et al. Adult female acne: a guide to clinical practice. An Bras Dermatol, 2019.
2. Carmina E, Dreno B, Lucky WA, et al. Female Adult Acne and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee. Journal of the Endocrine Society, 2022.
3. Słopień R, Milewska E, Rynio P, Męczekalski B. Use of oral contraceptives for management of acne vulgaris and hirsutism in women of reproductive and late reproductive age. Prz Menopauzalny, 2018.
4. Maloney JM, Dietze P Jr, Watson D, et al. Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial. Obstet Gynecol, 2008.
5. Koltun W, Maloney JM, Marr J, et al. Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3 mg administered in a 24/4 regimen: A pooled analysis. Eur J Obstet Gynecol Reprod Biol, 2011.
6. Arowojolu AO, Gallo MF, Lopez LM, et al. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev, 2012.
7. Palli MB, Reyes-Habito CM, Lima XT, et al. A single-center, randomized double-blind, parallel-group study to examine the safety and efficacy of 3 mg drospirenone/0.02 mg ethinyl estradiol compared with placebo in the treatment of moderate truncal acne vulgaris. J Drugs Dermatol, 2013.