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JEADV

DOI: 10.1111/jdv.13188

REVIEW ARTICLE

Treatment of adult female acne: a new challenge


no*
B. Dre
Department of Dermato-Cancerology, University of Nantes, Nantes, France
no. E-mail: brigitte.dreno@wanadoo.fr
*Correspondence: B. Dre

Abstract
Acne is affecting an increasing number of adult females and so can no longer be considered as a disease of adolescence. The disease has a greater negative impact on the quality of life of adult females than their younger counterparts.
Adult female acne may persist from adolescence or may have its rst occurrence once adulthood has been reached. The
clinical presentation and pathogenesis of adult female acne may be somewhat different to that of adolescent acne and
this may require a different treatment approach. Genetic and hormonal factors are thought to play key roles in the pathogenesis of adult female acne and the disease is characterized by a chronic evolution with frequent relapses requiring
long-term maintenance therapy. Fixed-dose retinoid/antimicrobial combinations may be of interest for the treatment of
adult female acne given that subgroup analysis of clinical trials has indicated that they are effective against both inammatory and non-inammatory lesions in these patients. These treatments may also be of interest, given the chronic
course of the disease in adult females, the high likelihood of the presence of antibiotic-resistant P. acnes and the poor
adherence of patients to other long-term therapies. Oral hormonal treatment or isotretinoin may be required in patients
with severe acne or disease that is refractory to other treatments. Additional clinical studies of acne treatments specically conducted in adult female patients are required to increase the evidence base on which future treatment recommendations can be based.
Received: 09 March 2015; Accepted: 14 April 2015

Funding source
This supplement was funded by Meda Pharma GmbH & Co. KG.

Conict of interest
BD has served as a consultant for Meda, Galderma, Fabre.

Introduction
Although acne is traditionally considered to be a disease which
affects teenagers, recent research has shown that acne is affecting
an increasing number of adults, particularly females.1 This skin
condition can have a substantial negative psychosocial and emotional impact on affected adults with older female patients
reporting a greater impact of acne on their quality of life than
younger patients.2,3 Acne is characterized by the presence of
inflammatory and non-inflammatory lesions and can lead to
some degree of facial scarring in up to 20% of those affected with
the likelihood of scarring increasing as the disease persists.4,5 The
aim of this article is to discuss the pathophysiological and clinical
evidence which indicates that adult female acne should be considered as a specific acne subtype distinct from adolescent acne
and to review topical and oral treatment options which may be
particularly suitable for treating acne in adult females.

Prevalence
Acne is a common disease in adult females. The overall prevalence rates of adult female acne have been reported in different

JEADV 2015, 29 (Suppl. 5), 1419

studies to range from 14% to 54%.69 These variations in prevalence rates are likely to be due to differences in the design of the
studies, with self-reported prevalence rates being higher than
those from clinical studies. The results of several age-stratified
surveys have shown that a substantial proportion of women
experience acne in adulthood, with the prevalence generally
declining with increasing age.812 Representative results from
one survey which documented the self-reported prevalence of
acne in 540 adult females are shown in Fig. 1. Of particular note,
over a quarter of the women included in this survey had acne
beyond the age of 40 as did 15% of those aged over 50.11 Two
surveys have shown that adult women in different age categories
have a significantly higher prevalence of acne than adult
men.10,11 In one of these surveys, a greater proportion of women
than men reported that their acne worsened in adulthood
(13.3% vs. 3.6%).11 One survey of 3305 French adult women
aged 2540 years reported that 49% of those with acne had
sequelae such as scars and/or pigmented macules.6
The prevalence of adult female acne is rising.13 One investigation into adult acne reported an increasing rate of referrals of

2015 European Academy of Dermatology and Venereology

Adult female acne

Figure 1 Prevalence of adult female acne (n = 540).11

patients aged over 25 years over the previous decade. The mean
age at which acne patients were referred increased from
20.5 years in 1984 to 26.5 years in 1994.14 This increasing prevalence of adult female acne has been postulated to be related to
factors such as the stress of modern life and sleep deprivation.15
The prevalence of adult female acne is different among
different ethnic groups. A study into 2895 women of different
ethnicities showed that acne was more prevalent in women of
darker skin types (African American, 37%; Hispanic, 32%) than
those with lighter skin types (Asian, 30%; Caucasian, 24%; Continental Indian, 23%).16 In Asian women, inflammatory acne
was more prevalent than non-inflammatory acne (20% vs.
10%), whereas in Caucasians, non-inflammatory acne was more
prevalent (14% vs. 10%). The prevalence of these two subtypes
of acne was similar in the other racial groups.16

Clinical presentation
There are two main subtypes of adult female acne. Persistent
acne is acne which continues from adolescence into adulthood
sometimes with periods of remission. This is the most common
subtype of adult female acne being present in approximately
80% of cases.1,17,18 Late-onset acne occurs in approximately 20%
of women with adult female acne and this subtype has its first
onset long after puberty, most often between the age of 21 and
25 years.1,17,18 Women with late-onset acne have significantly
fewer comedones and a lower proportion of comedones than
women with early-onset acne.19 Furthermore, adults with lateonset acne often have larger pores than individuals of the same
age without acne.18
The clinical presentation of adult female acne is typically considered to be different to that of adolescent acne. Adult acne

JEADV 2015, 29 (Suppl. 5), 1419

15

usually presents gradually and is mild-to-moderate in severity in


contrast to adolescent acne which may develop rapidly and present as severe disease.1,17 Adult female acne has traditionally been
viewed as presenting with two main clinical profiles.17 One profile consists of hyperseborrhoea and predominant diffuse noninflammatory lesions; these are mostly small closed comedones
with open comedones being rare. The other profile consists of
predominant inflammatory lesions. These can be either mild-tomoderate superficial inflammatory lesions or deep-seated, longlasting nodules and cysts on the lower third of the face, jaw-line
and neck (i.e. chin acne).
This traditional view of the clinical presentation of adult
female acne has recently been challenged by an observational,
prospective, international study in 374 adult females with acne.20
The results showed that 90% of women had acne involving multiple areas of the face (cheeks, forehead, mandibles, temples) and
they had a range of acne severity similar to that observed in adolescents. Most women had both inflammatory and non-inflammatory acne lesions, with just 6.4% having only inflammatory
lesions and 17.1% having only comedonal acne.20 In addition,
only 11.2% had acne localized specifically to the mandibular
area. Whilst the face is the most common site of disease presentation, extrafacial areas such as the upper back, chest and shoulders may be affected in up to 50% of adult female patients.20,21

Pathogenesis
Similar to adolescent acne, the pathogenesis of adult female acne
involves the interplay of excess sebum production, abnormal
keratinization within the follicle and bacterial colonization of
the pilosebaceous duct by Propionibacterium acnes.22 However,
the influence of these different factors may be somewhat different in adult female acne compared with adolescent acne and this
will ultimately necessitate a slightly different treatment
approach.
Studies have shown that genetic factors play a strong role in
the pathogenesis of adult female acne. Indeed, it has been shown
that a history of acne can be identified in at least one first degree
relative of 67% of adult females with acne aged 25 years or
older.21 And another study comparing 204 adults with persistent
acne with 144 non-acne controls showed that relatives of
patients with persistent adult acne had a significantly greater risk
of adult acne than relatives of people without acne (odds ratio:
3.93; 95% confidence interval: 2.795.51; P < 0.001).23
Hormonal factors are also likely to play a role in the pathogenesis of adult female acne. Studies have shown that 3985% of
adult women with acne have worsening of their acne in the days
before menstruation.6,11,14,2426 The rate of premenstrual acne
flares is significantly higher in older women (aged over 30 years,
53%) compared to younger adults (2033 years, 39%;
P = 0.03).26 The high frequency of seborrhoea in adult female
acne also suggests that hormonal factors in association with
genetic factors may be involved.21 However, studies of ovarian

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Table 1 Treatment recommendations for acne and alternatives for females


Global Alliance Acne Treatment Algorithm22
Mild
comedonal

Mild mixed and


papular/pustular

Moderate mixed and


papular/pustular

Moderate nodular

Severe nodular
conglobate

1st Choice

Topical
retinoid

Topical retinoid +
topical antimicrobial

Oral antibiotic + topical


retinoid  BPO

Oral antibiotic +
topical retinoid +
BPO

Oral isotretinoin

Alternatives for females

Oral anti-androgen +
topical retinoid/azelaic
acid  topical
antimicrobial

Oral anti-androgen +
topical retinoid/ 
oral antibiotic 
alternative
antimicrobial

High dose oral antiandrogen + topical


retinoid  alternative
topical antimicrobial

European Dermatology Forum29


Comedonal
acne

Mild-to-moderate
papulopustular acne

Severe
papulopustular/
moderate nodular acne

Severe nodular/
conglobate acne

High strength of
recommendation

Adapalene + BPO
BPO + clindamycin

Isotretinoin

Isotretinoin

Alternatives for females

Hormonal anti-androgens +
topical treatment
Or
Hormonal anti-androgens +
systemic antibiotics

Hormonal anti-androgens +
systemic antibiotics

and adrenal androgenic hormone levels in the serum of adult


females with acne have not shown any clear patterns of abnormalities.18 Whilst several significant increases in androgen levels
have been detected in women with adult-onset acne and hirsutism compared with healthy controls (e.g. luteinizing hormone,
follicle-stimulating hormone, testosterone, dihydroepiandrosterone sulphate [DHEA-S]), only the level of DHEA-S was shown
to be mildly to moderately elevated in women with adult-onset
acne without hirsutism compared with controls (266 vs. 201 g/
dL, respectively; P = 0.03).27 The lack of androgen hormone
abnormalities in adult female acne suggests that hormonal
receptors expressed by both sebocytes and keratinocytes may be
more sensitive to low levels of androgens in these patients and/
or there may be an increased local metabolism of androgens by
enzymes.17,18,28
Another key factor in the pathogenesis of adult female acne is
chronic activation of cutaneous innate immunity which may be
driven by the long duration of acne and higher levels of antibiotic-resistant P. acnes selected by previous long-term use of topical and systemic antibiotics.14,17

Treatment of adult female acne


The principal recommendations from the Global Alliance to
Improve Outcomes in Acne Group and the European Dermatology Forum for the treatment of female acne are shown in
Table 1 and discussed in more detail in the sections below.22,29
Adult female acne is characterized by a chronic evolution with
frequent relapses requiring long-term maintenance therapy.1

JEADV 2015, 29 (Suppl. 5), 1419

One study of 200 adults with acne aged over 25 years showed
that 82% relapsed after multiple courses of oral antibiotics and
32% relapsed after one or more course of oral isotretinoin.14
Other factors need to be taken into consideration when selecting
a treatment for adult females such as the slow response to therapy of this group of patients, their childbearing potential, the
increased likelihood of skin irritation and the high psychosocial
impact of the disease.30 Treatment choice is also guided by the
severity of acne, response to prior treatments, patient preferences and cost. The use of moisturisers and gentle, non-soap
cleansers with a pH close to that of the skin is recommended as
part of the therapeutic regimen for adult females with acne.30
Topical treatments

Topical retinoid monotherapy is recommended in adult females


with mild comedonal acne.22,29 However, it is important to recognize that older patients may be more susceptible to the skin
irritation that these agents may cause suggesting that formulations which are less irritating may be beneficial.18,31 Fixed-dose
combinations such as retinoid/antimicrobial combinations are
recommended in adult females with mild-to-moderate papulopustular acne.22,29 However, to date, there have not been any
clinical trials with topical treatments which have only included
adult females with acne.
Clindamycin 1% (as clindamycin phosphate 1.2%)/tretinoin
0.025% (Clin-RA) is a new fixed-dose topical combination treatment which was shown in a pooled analysis of three pivotal
12-week studies involving over 4500 acne patients to be safe and

2015 European Academy of Dermatology and Venereology

Adult female acne

(a)

(b)

17

(72.4% vs. 63.3%, 57.7% and 55.7% respectively; P < 0.03).


Clin-RA was also significantly more effective at reducing
non-inflammatory lesions than clindamycin in adult females
(55.2% vs. 43.8% respectively; P < 0.02).
In addition to its efficacy against inflammatory and noninflammatory lesions in adult females with acne, Clin-RA may
be a useful treatment option in this acne subgroup since it is not
associated with an increase in antibiotic-resistant P. acnes counts
and has even been shown to be effective at clearing clindamycin
resistant P. acnes.3335 These considerations are important given
that resistant P. acnes strains are common in adult females since
these patients have often been treated with several previous
courses of topical and systemic antibiotic therapy. Given that
adult females often have a slow response to treatment, adherence
to the therapeutic regimen is of particular importance. In this
regard, it is noteworthy that patient adherence to a fixed-dose
combination gel containing clindamycin and tretinoin was
higher than when patients applied the treatments separately.36
Oral treatments

Figure 2 Effect of Clin-RA and its components on adult male and


female acne: (a) inammatory lesions; (b) non-inammatory
lesions. *P < 0.03 vs. Clin-RA; **P < 0.02 vs. Clin-RA. Adult
dened as age 18 years. Clin-RA, clindamycin phosphate 1.2%/
tretinoin 0.025%.

effective in the treatment of acne when comedones, papules and


pustules are present.32 A subgroup analysis of the pooled results
including only adult patients aged 18 years or older (1194
females and 438 males) showed that the median percentage
reduction in inflammatory lesions with Clin-RA from baseline
to week 12 was numerically greater in adult females compared
with males (72.4% vs. 66.7%) as was the median percentage
reduction in non-inflammatory lesions (55.2% vs. 53.3%;
Fig. 2). Taking into consideration only the adult females,
Clin-RA was shown to be significantly more effective at reducing
inflammatory lesions than clindamycin, tretinoin and vehicle

JEADV 2015, 29 (Suppl. 5), 1419

Adult females with chronic deep-seated inflammatory lesions


may require systemic treatment. Long-term oral antibiotic
monotherapy is not recommended due to the growing problem
of antibiotic resistance.22,29 Furthermore, around 80% of adult
females with acne are refractory to this type of treatment.14
Oral contraceptives may be the first hormonal therapy used to
treat adult female acne when peripheral hyperandrogenemia is
noted specifically with flare-ups before menstruation. The third
generation progestins (e.g. desogestrel) have the lowest androgenic activity and so are preferred to progestins with intrinsic
androgenic activity which may cause worsening of acne.18 Since
hormonal therapy targets excess sebum production, they are
usually combined with treatments which are directed against the
other pathogenic factors of acne.30 Due to thromboembolic risk,
it is important to check whether the patient has any history of
thrombosis, pulmonary embolism, phlebitis or any other coagulation abnormalities before initiating treatment.
Anti-androgens (e.g. cyproterone and spironolactone) may
be added to contraceptive therapy if there is no improvement
in acne after 36 cycles.18 Spironolactone which has anti
androgenic activity (due to inhibition of 5-alpha reductase) is
typically reserved for adult females with acne that is refractory
to conventional treatment. Low doses of spironolactone are
generally used to improve the tolerability of this treatment
(50150 mg daily). If patients are using spironolactone as
monotherapy, then adequate contraception needs to be used
to avoid exposure to the drug during pregnancy since this can
lead to male fetal abnormalities.37 The therapeutic response
usually occurs within 2 months of starting therapy. One study
of 14 adult females with acne who had failed to respond to
isotretinoin showed that low-dose spironolactone 75150 mg/
day may be a useful therapeutic alternative. A clinical response

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(defined as 50% reduction in total lesions) was detected after


an average treatment period of 17 months in 50% of cases
with facial lesions and 37.5% of those with acne on the back.38
A retrospective chart review of 85 women with acne treated
with spironolactone 50100 mg/day also showed the usefulness
of this treatment either as a monotherapy or in combination
with other therapies. The patients were treated for up to
2 years with 33% being cleared of their acne and 33% having
a marked improvement.39 A small prospective study of 27
women with severe papular and nodulocystic acne showed that
combined therapy with an oral contraceptive and spironolactone 100 mg/day was effective with 85% of patients being
clear of lesions or having 75% lesion clearance after
6 months.40
Isotretinoin may be considered in adult female patients with
severe acne and in those with less severe acne that is refractory
to standard therapies.18 The starting dose recommended by the
European Directive for Prescribing Systemic Isotretinoin for
severe acne is 0.5 mg/kg/day with subsequent adjustments based
on efficacy and tolerability, and complete responses seen
46 months after treatment initiation. Patients initiating treatment with oral isotretinoin need to have a negative pregnancy
test and to use adequate contraception, given that this treatment
is a potent teratogen, according to the European recommendations.18 Positive predictors of therapeutic response to isotretinoin 0.5 mg/kg/day in a study of 32 adult females with acne
included a low body mass index, late-onset acne and not being a
tobacco user. This regimen given for 6 months was associated
with a complete response on the face in 59% of patients, on the
trunk in 80% of patients and on both the face and the trunk in
43% of patients.41 Low doses of 1020 mg/day and/or intermittent regimens may be suitable for adult female patients with less
severe acne that has not responded to other treatments.13,18 A
study of isotretinoin 0.5 mg/kg/day for 1 week out of every four
in 80 patients aged over 25 years with acne that was refractory to
antibiotic therapy showed that this intermittent regimen was
well tolerated and effective with 88% of patients being cleared of
their acne after 6 months.42

Conclusions
Adult female acne affects around 40% of women and the
prevalence of the disease in adult women is increasing. Adult
female acne is considered to be different to adolescent acne
both in terms of its clinical presentation and pathogenesis.
These differences necessitate alternative approaches to the
treatment of adult female acne. Fixed-dose retinoid/antimicrobial combinations may be of interest for the treatment of
adult female acne when comedones, papules and pustules are
present, given that subgroup analyses of clinical trials have
indicated their efficacy against inflammatory and non-inflammatory lesions in these patients. Fixed-dose combinations may
also be of interest for adult female acne taking into account

JEADV 2015, 29 (Suppl. 5), 1419

the chronic evolution of the disease, the high likelihood of


carriage of antibiotic-resistant P. acnes strains and the poor
adherence of patients to other long-term therapies. New retinoid-based formulations which are better tolerated may also
be beneficial for adult females, given that these patients may
be more susceptible to the skin irritation these agents cause.
Adult females presenting with more severe acne or acne that is
refractory to standard therapies may require hormonal treatment or isotretinoin. Future clinical studies of acne treatments
should be performed in separate populations of adult and
adolescent females to provide objective evidence of efficacy
and safety in these different acne subtypes.

Acknowledgements
Editorial assistance in the preparation of this manuscript was
provided by David Harrison, Medscript Communications,
funded by Meda Pharma GmbH & Co. KG.

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2015 European Academy of Dermatology and Venereology

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