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CASE REPORT

Oral stomatitis induced by endogenous progesterone: Case report

ELIANA M. MINICUCCI1, ALINE B. CARRENHO1, SILKE A. T. WEBER2,

FERNANDA M. BOMBINI1, RENATA A. M. A. RIBEIRO1, MARIANGELA E. A. MARQUES3,

& DANIEL A. RIBEIRO4

1Department of Dermatology and Radiotherapy,

2Department of Otorhinolaryngology and Ophthalmology,

3Department of

Pathology, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil, and4

Department of

Biosciences, Federal University of Sao Paulo, UNIFESP, Santos, Sao Paulo, Brazil

(Received 21 February 2008; revised 12 April 2009; accepted 27 April 2009)

Abstract

Oral stomatitis induced by endogenous progesterone is a rare clinical condition which may be associated with cutaneousinvolvement. That is probably due to the peak of progesterone production during the luteal phase of the menstrual cycle. Inthe present case report, a 21-year-old patient displayed recurrent ulcerative lesions located on the buccal mucosa or the upperlip, on a monthly basis since the age of 15. Such lesions would always manifest themselves on the second day until the end ofthe menstrual cycle.

Keywords: Oral stomatitis, progesterone

Introduction

Hypersensitivity induced by female sexual hormonesis a rare clinical condition in which the patient

develops a hypersensitivity reaction to endogenous

progesterone. Such pathological condition occurs in

patients ranging from 16 to 48 years of age with a

predominance of young people [1]. Clinical manifes-

tation is triggered every month during the luteal phase

of the menstrual cycle, when the peak of progesterone

production is reached. The clinical manifestations are

variable [2] and include urticaria [3,4], erythema

multiforme like-reaction [5], and eczema [6]. How-

ever, after the menstrual cycle, lesions disappear

spontaneously. To date, a large number of studies

have addressed clinical manifestations, especially onthe skin, induced by endogenous progesterone. To

the best of our knowledge, there are a few case

reports addressing lesions specifically in the oral

mucosa [2]. Therefore, such a circumstance justifies

this case report as well as others; and, by taking into

consideration, the current article describes a case

report of oral stomatitis induced by endogenous

progesterone.

Case report

A 21-year-old Caucasian woman was referred to theDepartment of Dermatology, at the Ambulatory

Care Center of Stomatology at Botucatu Medical

School Sao Paulo State University (UNESP),

Brazil complaining of ulcerative lesions in the

perioral region, buccal mucosa, and upper lip

(Figures 1 and 2). The patient reported that those

lesions were painful. She also added that they had

first appeared when she was 15 years old, on a

monthly basis. However, the general conditions of

health were good. Under clinical examination, no

skin abnormalities were found. No drugs were used

for minimizing the symptomatology. To exclude

herpes as putative diagnosis, Tzancks test wasperformed [7]. The result was negative; and, as a

consequence, incisional biopsy was performed. Mi-

croscopically, the lesion had sub- and intraepithelial

vesicles associated with necrosis in the basal layer

(Figure 3). Moderate inflammatory infiltrate consist-

ing of lymphocytes, neutrophils and eosinophils was

present, with some of the inflammatory cells located

in the perivascular region (Figure 3). Skin testing

Correspondence: Daniel Araki Ribeiro, DDS, PhD, Departamento de Biociencias, Universidade Federal de Sao Paulo UNIFESP, Av. Ana Costa 95, 11060-

001 Santos, SP, Brazil. Tel: 55-1332218058. Fax: 55-1332232592. E-mail: daribeiro@unifesp.br

Gynecological Endocrinology, August 2009; 25(8): 543545

ISSN 0951-3590 print/ISSN 1473-0766 online 2009 Informa UK Ltd.

DOI: 10.1080/09513590903015585

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with estrogen (1 mg/ml) and Depo-Provera (1 mg/

ml), a derivative of progesterone, was performed and

no reaction in skin areas developed after 48-h

evaluation. Taken as a whole, these findings sup-

ported the final diagnosis of oral stomatitis induced

by endogenous progesterone. After that, the patient

followed a consultation with her gynecologist, in

which it was prescribed Tamoxifen (Nolvadex), an

antiestrogen agent, at a dosage of 20 mg/day for 2

months as described elsewhere [8]. The patient

reported that her clinical symptoms began to

decline gradually over a few weeks, and no recur-

rences were detected up to now (8 months after

initial diagnosis).

Discussion

Autoimmune reaction triggered by endogenous

progesterone is a rare clinical condition. The picture

is characterized by recurrent cutaneous lesions

during the luteal phase of the menstrual cycle, when

the levels of endogenous progesterone are increased.

Patients have reported cyclic lesions mainly in the

skin. Such lesions appear before menstruation and

remain even after the menstrual cycle is over [2]. In

this case report, we have been able to report the

instance of a woman with oral manifestationsinduced by endogenous progesterone. The lesions

occurred in the perioral region, buccal mucosa, and

upper lip with symptomatology. The early clinical

pattern seemed to be a herpes infection, but Tzancks

test presented a negative result. Moghadam et al. [8]

have postulated that lesions induced by endogenous

progesterone disappear 1 week after the menstrual

cycle. Other authors have assumed hypersensitivity to

be induced by endogenous progesterone, such as

anaphylaxis during the menstrual cycle [9]. All

symptoms disappear after some days [10,11]. Skin

testing with estrogen (1 mg/ml) and Depo-Provera

(1 mg/ml), a derivative of progesterone, was per-formed and no reaction in skin areas developed after

48-h evaluation. There is no relationship between

oral stomatitis induced by progesterone and positive

response in this test. Therefore, final diagnosis was

perfomed taking into consideration the clinical

history only.

The underlying mechanisms by which endogenous

progesterone becomes antigenic remain unknown so

far. It has been suggested that abnormalities in the

composition of the hormone are present in women

able to develop such autoimmune reaction [11]. The

occurrence of antibodies against endogenous pro-

gesterone has been demonstrated in patients pre-senting history of oral ulcers since their first

menstruation [12]. Another possibility is a cross-

reaction between endogenous progesterone and

circulating antibodies produced by putative antigen

present in the body, such as in the case of a viral

infection [11,12]. Growing evidence suggests that

synthetic progesterone may stimulate antibodies

against endogenous progesterone in contraceptive

users [13].

Therapy is the use of anti-estrogenic drugs, such as

Tamoxifen [14], estrogens (Premarin), which are

Figure 2. Clinical aspects of lesions in the buccal mucosa.

Figure 3. Photomicrography of the lesion (H.E. stain, 640

magnification).

Figure 1. Clinical aspects of lesions in the upper lip.

544 E. M. Minicucci et al.

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able to interrupt the ovulation process as well as the

production of endogenous progesterone [2,3].

Nevertheless, several patients do not undergo any

therapy [15]. In this case, the patient received

Tamoxifen (Nolvadex) after establishing the final

diagnosis, at a dosage of 20 mg/day for 2 months as

described elsewhere [8]. The patient reported that

her clinical symptoms began to decline gradually

over a few weeks, and no recurrences were detected

up to now (8 months after initial diagnosis).

As a conclusion, oral stomatitis induced by

endogenous progesterone is a rare disease. Histolo-

gical confirmation of the clinical diagnosis is not

essential in most cases. Gynecologists, dentists and/

or endocrinologists should be aware of such

concerns.

Declaration of interest: The authors report no

conflicts of interest. The authors alone are respon-

sible for the content and writing of the article.

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