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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

Condition category

Condition code

Metabolic and Endocrine

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]

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]

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]

At 3 rd and 6 th months after the start of treatment.

Secondary outcome [1]

Changes in ovarian morphology (Policystic ovary or not by ultrasonography)

Timepoint [1]

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]

Changes in serum androgen profiles regarding total testosterone, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone

Timepoint [2]

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

Sex

Females

Can healthy volunteers participate?

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

10/08/2006

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]

Turkey

State/province [1]

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Dr Kiymet Handan Kelekci

Address [1]

Belediye evleri mah
Vilko sitesi No: 45
84220, Cukurova, Adana

Country [1]

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]

Individual

Name [1]

Dr Bulent Yilmaz

Address [1]

Camlitepe mah, Taskent Sokak, 26/8, 06600, Kurtulus, Ankara

Country [1]

Turkey

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research and Ethics Committee of the Numune Education and Research Hospital, Adana, Turkey

Ethics committee address [1]

Ethics committee country [1]

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Bulent Yilmaz, MD

Address

Camlitepe mah, Taskent Sokak, 26/8, 06600, Kurtulus, Ankara

Country

Turkey

Phone

+9005053574351

Fax

[email protected]

Contact person for scientific queries

Name

Bulent Yilmaz, MD

Address

Camlitepe mah, Taskent Sokak, 26/8, 06600, Kurtulus, Ankara

Country

Turkey

Phone

+9005053574351

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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No additional documents have been identified.

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