danazol versus oil of evening primrose in the treatment of mastalgia

Original
Article
DANAZOL VERSUS OIL OF EVENING PRIMROSE
IN THE TREATMENT OF MASTALGIA
SUGHRA PARVEEN, GHULAM SARWAR*, MASHOOQUE ALI, GHULAM ASGHAR CHANNA
Department of General Surgery, Ward-26, Jinnah Postgraduate Medical Centre, Karachi
Department of Anatomy*, Sindh Medical College & Dow University of Health Sciences, Karachi
ABSTRACT
Objective: To evaluate the efficacy of Danazol and Oil of Evening Primrose (OEP) in the treatment of Mastalgia,
and to note their undesirable effects during the course of treatment.
Design & Duration: An open, non-randomized, comparative study, carried out from Nov. 2004 to Nov. 2005.
Setting: Department of General Surgery, Surgical Unit-III (Ward 26), Jinnah Postgraduate Medical Centre, Karachi.
Patients: A total of 100 female patients with moderate to severe breast pain who visited the Out-patient Surgical
Department of Jinnah Postgraduate Medical Centre, Karachi.
Methogology: After clinical evaluation, investigations and informed consent, all patients were assigned to two groups
alternatively. Mastalgia in all the patients was gauged before and during the treatment according to the Cardiff
Breast pain Score (CBS). Patients with discrete lumps, nipple discharge, lactation, pregnancy and breast abscess
were excluded from the study. Group-I (n=50) patients were given Danazol 100mg b.i.d per oral and Group-II (n=50)
Efamol (Oil of evening primrose) 500mg b.i.d per oral for three months periods. All patients were seen at 4 and 12
weeks, their level of mastalgia assessed and information sought about adverse effects of the drug.
Results: Out of the 100 patients, 70% belong to the age group 15-25 years, 20% to 26-35 years and 10% beyond
35 years of age. The overall response with Danazol was 76% in contrast to 68% response in the patients treated
with OEP. The patients who were treated with Danazol showed 32% distressing but reversible side effects as compared
to 12% in OEP which were not distressing and also reversible.
Conclusion: Danazol offers good pain control in mastalgia but with distressing side effects, where as Oil of Evening
Primrose (OEP) also showed good pain control but without much distressing side effects.
KEY WORDS: Mastalgia, Danazol, Evening Oil of Primrose, Adverse Effects
INTRODUCTION
Mastalgia or breast pain, is a common and often distressing
complaint, that occurs in upto 70% women at some
stage of their life 1 . It is a encountered both at the primary
care and surgical out-patient settings in the subcontinent
2 . Inadequate, delayed and incompetent management
of breast pain results in unnecessary physical, emotional
and financial strains on the patients and the health care
system. Beside discomfort, perhaps the worst thing
Correspondence:
Dr. Sughra Parveen, Assistant Professor Surgery,
Flat No.4, Block - IVA, Doctor’s Colony,
Jinnah Postgraduate Medical Centre, Karachi.
Phones: 0300-3509004.
about this condition is the incorrect belief of the patients
that this is a symptom of the onset of the breast cancer 3 .
However, because of this wrong belief and the fear of
breast cancer, most patients present to the clinics and
seek medical advice 4 .
Clinical management of breast pain depends upon the
type of Mastalgia 5 viz. Cyclical, Non-Cyclical and Extra
mammary Mastalgia. The cause of cyclical breast pain
is unclear, though one theory popular in Europe suggests
that higher than normal levels of the hormone prolactin
may be involved, while another attributes the condition
to an imbalance of essential fatty acids. In contrast there
is no relation to the menstrual cycle in the Non-Cyclical
mastalgia, which is responsible for symptoms in a quarter
of such patients referred to the clinics 6 . The most
important factors in the evaluation of breast pain include
taking a good and thorough history taking and examination
and carrying out appropriate investigations 7 .
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Danazol Vs. OEP in Mastalgia S. Parveen, G.
Score
I
II
III
IV
Excellent response with no residual pain
Substantial response but with some
residual pain, considered by the patient
to be bearable
Poor response with substantial residual
pain
No response at all
Table I. Cardiff Breast pain Score (CBS)
Most (75%-85%) of the patients generally require no
treatment 8 . In the remaining women pain remain constant
and interfere with the day to day activities requiring
some sort of treatment.
The purpose of this study was to compare the results
of Danazol and Oil of Evening Primrose (OEP) in respect
to efficacy, rapidity of response and adverse effects
in the treatment of mastalgia.
PATIENTS & METHODS
Response
This study was conducted in the Out-patient Dept. of
Surgical Unit III (Ward-26) at Jinnah Postgraduate
Medical Centre, Karachi from November 2004 to November
2005 on 100 female patients with moderate to
severe breast pain. A thorough history was taken and
a detailed clinical examination was carried out in all
the patients. Imaging modalities were done where necessary
to rule out benign breast disease and occult carcinoma.
After taking informed consent, all patients were
allocated to the two groups, alternatively. All patients
were gauged according to Cardiff Breast pain Score
(CBS) as shown in Table I. Patients with discrete lumps,
nipple discharge, lactation, pregnancy and breast abscess
were excluded from the study.
Side effect
Altered taste
Nausea / vomiting
Abdominal bloating
Menstrual problem
Weight gain
Hirsutism
Group-I (comprising 50 patients) was given Danazol
100mg b.i.d per oral, while Group-II (also comprising
50 patients) was given Efamol (Oil of Evening Primrose)
500mg b.i.d per oral for a three months period. Response
of the treatment was gauged according to the Cardiff
Breast pain Score at 4 weeks and 12 weeks. Information
was also sought about the adverse effects of the drugs.
No change was made in the treatment before three
months. After collecting the data, results were compared
and analyzed by the student t-test and chi-square test.
RESULTS
Group-I
(Danazol)
Table III. Side effects of the Drugs
Out of the 100 patients, 70% belong to the age group
15-25 years, 20% to 26-35 years and 10% beyond 35
years of age. Fifty two percent women (mean age 28
years) had cyclical mastalgia whereas 48% (mean age
34.5 years) had non-cyclical mastalgia.
Amongst those patients who used Danazol, Grade-I
response was observed in 22 (44%) patients at 4 weeks
and 38 (76%) patients at 12 weeks in comparison to
OEP patients with 36% at four and 68% at 12 weeks
(Table II). Adverse effects observed at the end of the
treatment were 32% in Danazol Group which were distressing
but reversible and 12% in OEP Group which
were not distressing and reversible (Table III).
--
--
--
6
1
1
Group-II
(OEP)
1
1
1
--
--
--
Table II. Treatment response in Mastalgia at 4 weeks and 12 weeks
Grade
Response
Response at 4 weeks
Response at 12 weeks
Gp.I-Danazol Gp.II-OEP Gp.I-Danazol Gp.II-OEP
I
II
III
IV
Excellent
Substantial
Poor
None
22 (44%)
18 (36%)
06 (12%)
04 (08%)
18 (36%)
12 (24%)
12 (24%)
08 (16%)
38 (76%)
06 (12%)
06 (12%)
-- (00%)
34 (68%)
06 (12%)
06 (12%)
04 (08%)
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Danazol Vs. OEP in Mastalgia S. Parveen, G.
DISCUSSION
Mastalgia is a common and enigmatic condition; it was
described in the medical literature as early as 1829 9 ,
but was known to medical practitioners much earlier 10 .
Amongst a large cohort of 2400 women enrolled in a
health maintenance organization in the United States
pain was the most common breast symptom during a
ten years period, promoting medical evaluation and
accounting for 47% of breast related visits 11 . Similarly
in a study of 1171 women attending an Obstetrics and
Gynecology clinic in United States, 69% experience
regular premenstrual breast discomfort 12 .
Currently various treatment modes are in practice for
the management of breast pain but most are insufficient.
This study was conducted with the aim of evaluating
effectiveness, compliance and adverse effects of drugs
in female patients treated for breast pain. The two agents
used for comparison included Danazol and Evening Oil
of Primrose (EOP).
Evening Oil of Primrose is extracted from the seeds of
Evening Primrose plant (Oenotheria Bennis) 13 . Evening
primrose is a versatile plant and can be found near
streams, mountains, roadsides and even in the middle
of deserts. It is referred as evening primrose because
the flower blooms in the evening. Its oil is thus a natural
product rather than a drug, which is rich in essential
fatty acids like linolenic acid. The body converts linolenic
acid into a hormone like substance prostaglandin
(Pg) especially PgE1 14 , that helps in the reduction of
inflammatory cells. The product is usually prescribed
in a dose of 500mg b.i.d per oral 1 , though various international
studies have used 2-3 grams daily. The optimal
dose and duration of treatment with EOP is not known 15 .
The first study of EOP was conducted in Cardiff Mastalgia
Clinic by University of Wales College of Medicine
and published in the Journal of the Royal Society
of Medicine in 1992.
Danazol is a synthetic testosterone which binds to the
progesterone and androgen receptors, though the precise
mechanism of action in the treatment of mastalgia is
unknown. The main factors limiting the use of Danazol
is its spectrum of side effects. Majority (59%-92%) of
women treated with Danazol (200mg orally per day)
in controlled clinical trials gets relief in breast pain and
tenderness. In our study the results showed Danazol to
be significantly effective (76%) in the treatment of mastalgia
as compared to 68% effectiveness of EOP, which
is quite comparable. However, the side effects of Danazol,
which were 32% in comparison to very low side
effects of EOP that is 8% limits its usage in the treatment
of mastalgia.
The response rate with Danazol has been reported as
70% in cyclical mastalgia and 31% in non-cyclical mastalgia;
although a relapse rate of 50% was also reported
in the same study 16 . Another study describes a 79.4%
success rate in cyclical and 77.7% for non-cyclical
mastalgia, but the side effects especially nausea and
irregular menses were frequent (20.6%) with Danazol
therapy 17 .
Qureshi and Sultan 1 showed a clinical response of 64%
with EOP, which is similar to that of ours, though other
studies report a decreased overall response rate of 58% 18 .
Shabbir 19 also advocates using a protocol of reassurance,
adherence to low fat methyl xanthine restricted diet and
dietary supplementation with 500mg/day of evening
primrose oil as the first line of treatment in mastalgia.
CONCLUSION
This study has shown that Danazol (Danocrine) offered
good pain control in mastalgia with distressing side effects
which were reversible, whereas the Oil of Evening
Primrose also showed good pain control but without
any distressing side effects.
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Danazol Vs. OEP in Mastalgia
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S. Parveen, G
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