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Letters to the Editor
Cyproterone acetate as a treatment for moderate-to-severe
inappropriate sexual behavior in dementia
Dear Editor,
While dementia is mainly characterized by cognitive
alterations, behavioral and psychological symptoms are
very common, increasing the risk of poor outcome.
The most common alterations reported in dementia
patients are apathy and decreased sexual interest.1
Nevertheless, inappropriate sexual behavior (ISB) has
also frequently been described in many cases of
dementia, and it has increasingly been recognized as
an important symptom.2 ISB is more frequent among
institutionalized patients and those with greater cogni-
tive impairment. 3 Given the profoundly disruptive
nature of ISB, especially to caregivers and other resi-
dents in nursing facilities, there have been efforts in
the appropriate management of ISB. The general con-
sensus has been that non-pharmacological interven-
tions, including an environmental or behavioral
approach, should be prioritized due to safety and ethi-
cal issues.2 Only when such efforts are not responsive,
a pharmacological approach should be considered.
However, there has not been any randomized con-
trolled trial regarding the effects of medications on
ISB, with only case reports to date.4
Hormonal agents are one option for ISB. A number
of case reports have shown that they achieved a signifi-
cant reduction in ISB patients sexually acting out
post-administration of hormonal agents that lowered
testosterone production.5 Cyproterone acetate (CPA) is
a synthetic progestin and anti-androgen that works by
inhibiting the interaction between endogenous andro-
gens and androgen receptors, as well as by reducing the
biosynthesis of androgens.5 In the present study, we
investigated whether CPA is an effective and safe phar-
macological approach to reduce moderate-to-severe
ISB in older patients with dementia.6 The study proto-
col was approved by the institutional review board of
Seoul National University Bundang Hospital and con-
forms to the provisions of the Declaration of Helsinki.
A consecutive series of 10 older male patients with
dementia, who visited the Department of Neurology of
Seoul National University Bundang Hospital between
April 2014 and June 2017, were treated with CPA. They
showed moderate-to-severe ISB, which corresponded
to stage 2 or higher on the overt behavior scale of inap-
propriate sexual behavior category.6 In these patients, a
non-pharmacological approach was used, without
much success, before administration of CPA. Table 1
366 |
shows the patient characteristics, description of ISB
and dosage of CPA prescribed. CPA effectively reduced
ISB in all patients. Five patients responded to 25 mg of
CPA twice a day, whereas four patients responded to
50 mg of CPA twice a day. One patient with Alzhei-
mer’s disease responded to 75 mg of CPA twice a day;
but the medication was stopped as a result of depres-
sion and fatigue, which disappeared soon after discon-
tinuation of CPA. There were no laboratory
abnormalities or other relevant side-effects associated
with CPA in all patients.
The present findings show that CPA is an effective
pharmacological strategy for managing ISB. A previous
case report suggested CPA as a potent agent for ISB. In
their report, 10 mg of CPA was used with beneficial
effects in two men with dementia-related ISB after
unsuccessful attempts with antipsychotic or sedative
medication.7 However, another case report described
unsuccessful CPA treatment in a 70-year-old dementia
patient with a dosage of 50 mg twice a day; this patient
developed adverse side-effects – impairment of mobility
– that recovered after discontinuation.8 The possible
side-effects of CPA include fatigue, gynecomastia,
weight gain, dry skin, hair loss, depressive mood, sleep-
iness, hepatocellular damage, and rarely, thromboem-
bolism. Although the use of CPA in the geriatric
population might be associated with such disadvan-
tages, there have not been any reported cases of major
side-effects in dementia patients for the purpose of
behavioral management.9,10 To date, CPA has already
been used extensively in older male patients for the
treatment of prostate cancer, and most side-effects have
been shown to emerge with a dosage of >300 mg/day.8
CPA can also be used to control aggression (excluding
hypersexuality-related behaviors) in dementia.9 There
has been a case report describing the successful man-
agement of aggression in a patient with Alzheimer’s dis-
ease, who initially failed other medications.9 A
randomized double-blind trial that included 27 partici-
pants with Alzheimer’s disease comparing CPA with
haloperidol has also showed that CPA might be more
effective in controlling aggression and was associated
with fewer side-effects.10 CPA can be an effective alter-
native to antipsychotic drugs, especially in patients with
dementia with Lewy bodies, as introducing antipsy-
chotic drugs can increase the risk of worsening parkin-
sonian symptoms.
In the present pilot study, we showed that CPA can
be an effective treatment method for moderate-to-
© 2018 Japan Geriatrics Society
 Letters to the Editor

Table 1 Demographic characteristics of patients, description of inappropriate sexual behavior, and dosage of
cyproterone acetate used

Case Age Sex Diagnosis CDR MMSE ISB Successful

no. (years) dosage
of CPA
1 77 M AD 1 20 Inappropriate request for 25 mg twice a
having sexual relations day
with the spouse, exposure
of genitals in public
2 79 M AD 0.5 25 Touching young women on 50 mg twice a
the street as well as day
hugging and kissing
female staff in the day
care center
3 78 M DLB 1 19 Inappropriate request for 25 mg twice a
having sexual relations day
with the spouse
4 78 M AD 1 20 Inappropriate request for 50 mg twice a
having sexual relations day
with the spouse
5 84 M Mixed dementia 1 20 Delusion of being loved by 25 mg twice a
(AD with subdural female staff of the post day
hemorrhage) office and clinic as well as
request for having sexual
relations with his
daughter-in-law
6 89 M DLB 1 16 Touching breast of female 25 mg twice a
staff and masturbation in day
the day care center
7† 66 M AD 0.5 21 Inappropriate request for 75 mg twice a
having sexual relations day
with the spouse
8 75 M VD 1 21 Inappropriate request for 50 mg twice a
having sexual relations day
with the spouse
9 83 M DLB 0.5 27 Inappropriate request for 50 mg twice a
having sexual relations day
with the spouse
10 82 M AD 0.5 24 Touching breast of female 25 mg twice a
staff and masturbation in day
the nursing home
†
Administration of cyproterone acetate (CPA) was discontinued as a result of depression and fatigue. AD, Alzheimer’s dementia;
CPA, cyproterone acetate; DLB, dementia of Lewy body; ISB, inappropriate sexual behavior; MMSE, Mini-Mental State
Examination; M, male; NPH, normal pressure hydrocephalus; VD, vascular dementia.

severe ISB patients with dementia, with a dose of Min Ju Kang, Jeewon Suh,
25–50 mg twice a day. We also showed that CPA treat- SangYun Kim and Young Ho Park
ment with this dosage had a favorable side-effect pro- Department of Neurology, Seoul National University Bundang
file. Further research, with a large-scale sample, is still Hospital, Seongnam-si, Korea
required to better elucidate the efficacy of ISB.

References
Disclosure statement
1 Wright LK. Affection and sexuality in the presence of Alzheimer’s
The authors declare no conflict of interest. disease: a longitudinal study. Sex Disabil 1998; 16: 167–179.

© 2018 Japan Geriatrics Society | 367

 Letters to the Editor
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368 |
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© 2018 Japan Geriatrics Society