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Trial registered on ANZCTR


Registration number
ACTRN12609000604202
Ethics application status
Approved
Date submitted
16/07/2009
Date registered
21/07/2009
Date last updated
21/07/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Combined oral contraceptives plus spironolactone or cyproterone acetate for hirsutism: Randomized comparison of three regimens
Scientific title
Randomized prospective study to compare the efficacy and safety of combined oral contraceptives plus spironolactone or cyproterone acetate for the treatment of hirsutism
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The treatment of moderate and severe hirsutism 237264 0
Condition category
Condition code
Metabolic and Endocrine 239586 239586 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
According to a computer generated randomization table, women were randomly assigned to three treatment groups: Thirty mcg ethinyl estradiol plus 3 mg drospirenone (Yasmin 'Registered Trademark', Schering AG, Berlin, Germany)/cyproterone acetate 50 mg (Androcur 'Registered Trademark', Schering AG, Berlin, Germany) was given in Group I (n=45), 30 mcg ethinyl estradiol plus 3 mg drospirenone (Yasmin 'Registered Trademark',Schering AG, Berlin, Germany)/Spironolactone 100 mg (Aldactone 'Registered Trademark', Aris, Istanbul, Turkey) was given in Group II (n=44) and 35 mcg ethinyl estradiol plus 2 mg cyproterone acetate 35 (Diane 'Registered Trademark', Schering AG, Berlin, Germany)/cyproterone acetate 50 mg (Group III; n=45). Randomization was carried out blindly with respect to the patient’s clinical features while patients were not blind to treatment regimens. Patients were told to take combined oral contraceptives (pills containing both estrogens and progesterones) for 21 days as oral blisters, followed by a 7-day pill-free period. In group I and III, cyproterone acetate (2x50 mg/day) was recommended to be taken for the first 14 days of the cycle while Spironolactone was advised with the regimen of 100 mg/day during treatment period (everyday for 6 months) once per day only as oral capsules. Therapy was were started on the 1st day of the menstrual cycle and continued for 6 months.
Intervention code [1] 236947 0
Treatment: Drugs
Comparator / control treatment
Treatment groups are consisted of 3 groups and all of them were active as described above
Control group
Active

Outcomes
Primary outcome [1] 238380 0
The decrease in hirsutism score, which was always evaluated by the same physician by the modified Ferriman-Gallwey score, who was blinded to treatment groups.
Timepoint [1] 238380 0
At 3 rd and 6 th months after the start of treatment.
Secondary outcome [1] 244830 0
Changes in ovarian morphology (Policystic ovary or not by ultrasonography)
Timepoint [1] 244830 0
At 3 rd and 6 th months after the start of treatment. It was always evaluated by the same physician using ultrasonography, who was blinded to treatment groups.
Secondary outcome [2] 244831 0
Changes in serum androgen profiles regarding total testosterone, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone
Timepoint [2] 244831 0
They were obtained at the early follicular phase of patents' spontaneous menstruation before, and on three and six months after treatment using radioimmunoassay commercial kits.

Eligibility
Key inclusion criteria
Nulligravid women with moderate-to-severe hirsutism, non-pregnant women or women who do not wish to become pregnant, no smoking, no history of breast cancer and endometrium cancer, no active liver disease, no history of thromboembolic disease, no treatment for hirsutism before.
Minimum age
17 Years
Maximum age
35 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects with thyroid disease, diabetes mellitus, adrenal disorders,
hyperprolactinemia, or any other disorder were excluded from the study. Women with hirsutism due to androgen excess such as late-onset congenital adrenal hyperplasia were not included in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Group allocation was predetermined and placed in consecutively numbered opaque, sealed envelopes. The next consecutive envelope was drawn after the patient consented to randomization.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization was performed with use of a computer generated random number table.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 1884 0
Turkey
State/province [1] 1884 0

Funding & Sponsors
Funding source category [1] 237338 0
Self funded/Unfunded
Name [1] 237338 0
Dr Kiymet Handan Kelekci
Address [1] 237338 0
Belediye evleri mah
Vilko sitesi No: 45
84220, Cukurova, Adana
Country [1] 237338 0
Turkey
Primary sponsor type
Individual
Name
Dr Sefa Kelekci
Address
Belediye evleri mah
Vilko sitesi No: 45
84220, Cukurova, Adana
Country
Turkey
Secondary sponsor category [1] 236825 0
Individual
Name [1] 236825 0
Dr Bulent Yilmaz
Address [1] 236825 0
Camlitepe mah, Taskent Sokak, 26/8, 06600, Kurtulus, Ankara
Country [1] 236825 0
Turkey

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239456 0
Human Research and Ethics Committee of the Numune Education and Research Hospital, Adana, Turkey
Ethics committee address [1] 239456 0
Ethics committee country [1] 239456 0
Date submitted for ethics approval [1] 239456 0
Approval date [1] 239456 0
Ethics approval number [1] 239456 0

Summary
Brief summary
Hirsutism is a distressing and relatively common endocrine problem in women which may prove difficult to manage. Treatment consists of suppressing ovarian or adrenal androgen secretion, or blocking androgen actions in the skin. The major drugs used are gonadotropin-releasing hormone agonists, combined oral contraceptives (COCs), and steroidal (cyproterone acetate(CPA) and spironolactone) or nonsteroidal (flutamide and finasteride) antiandrogens.[1]
COCs have been used to treat androgenic symptoms because of their ability to suppress the secretion of gonadotrophins, ovarian or adrenal androgens, and to stimulate the hepatic synthesis of sex hormone-binding globulins (SHBG) resulting in decreased bioactive testosterone. COCs are more effective when associated with antiandrogens. Moreover, oral contraceptives will reduce the risk of irregular bleeding and provide adequate contraception, particularly in the face of the teratogenic potential of antiandrogens, and will potentiate the effectiveness of therapy by suppressing circulating androgen levels.
Antiandrogens prevent androgens from expressing their activity at target tissues. Spironolactone is an aldosterone-antagonist diuretic, with antiandrogenic properties. It competitively inhibits the interaction of dihydrotestosterone (DHT) with its intracellular androgen receptors. Additionally, spironolactone inhibits 5a-reductase activity in the target tissues and inhibits the cytochrome P450 system (17-hydroxylase and 17,20-lyase activities) within the ovaries and in the adrenals. The drug can be used alone in doses of 100 to 200 mg daily or in combination with the COCs.
CPA is a synthetic progestogen derived from 17a-hydroxyprogesterone. It has antigonadotropic and antiandrogenic peripheral activity. It inhibits the activity of testosterone and DHT by binding to intracellular receptors and decreases ovarian androgen secretion by inhibiting LH release. Furthermore, CPA decreases 5a-reductase activity and increases metabolic clearance of testosterone. It is most conveniently administered as the COC which is effective in controlling acne and hirsutism alone, or in combination with spironolactone 100 mg daily.
To the best our knowledge, there is no head to head comparison of efficay of different combinations of COCs and antiandrogens in the treatment of hirsutism in the medical literature. Therefore, our aim was to compare the efficacy and safety of three different combinations of COCs and antiandrogens in the treatment of moderate and severe hirsutism.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29905 0
Address 29905 0
Country 29905 0
Phone 29905 0
Fax 29905 0
Email 29905 0
Contact person for public queries
Name 13152 0
Bulent Yilmaz, MD
Address 13152 0
Camlitepe mah, Taskent Sokak, 26/8, 06600, Kurtulus, Ankara
Country 13152 0
Turkey
Phone 13152 0
+9005053574351
Fax 13152 0
Email 13152 0
drbulentyilmaz@yahoo.com
Contact person for scientific queries
Name 4080 0
Bulent Yilmaz, MD
Address 4080 0
Camlitepe mah, Taskent Sokak, 26/8, 06600, Kurtulus, Ankara
Country 4080 0
Turkey
Phone 4080 0
+9005053574351
Fax 4080 0
Email 4080 0
drbulentyilmaz@yahoo.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary