Significant Reduction of Hyperandrogenism by Long-Term Treatment with Cyproterone Acetate and Ethinyl Estradiol Combination in PCOS

22 Nov, 21

Introduction

Androgenic manifestations are a major concern in the clinical management of polycystic ovary syndrome (PCOS). Hyperandrogenism manifests as acne, hirsutism and seborrhea. Oral contraceptive preparations have been widely used in women with PCOS. Cyproterone acetate (CPA), is a progestin, with antigonadotrophic and antiandrogenic peripheral activity. Combination of CPA and ethinylestradiol (EE) has been shown to induce significant increase in plasma concentrations of Sex Hormone Binding Globulin (SHBG) as well as decrease in the LH/FSH ratio and in adrenal and ovarian androgens.

Aim

The long-term effects (36 cycles without interruption) of the monophasic combination containing 0.035 mg of EE and 2 mg of CPA (EE35-CPA) on the hormonal and clinical parameters were assessed in women with PCOS.

Method

Study Design

Prospective study.

Patient Profile

Women with clinical diagnosis of PCOS
Mean age 22.8+3.8 years
Average body mass index of 21.5
Did not wish to become pregnant
No contraindications to oral contraceptives

Treatment Strategy

The study population comprised 66 women with acne in 100%, hirsutism in 72.7% and seborrhea in 83.3%.
The clinical and endocrine parameters were evaluated at baseline.
Ferryman Gallwey score was used to grade hirsutism as mild, moderate and severe with scores 6-9, 10-14 and 15-17 respectively.
Clinical and endocrine evaluation was repeated at 6^th, 12^th, 18^th, 24^th and 36^th treatment cycles and at 6^th, 12^th, 24^th and 36^th treatment cycles respectively.
A pelvic ultrasonographic scan was done at baseline and at the end of study.
All the patients took the EE35-CPA for 36 cycles without interruption.
Follow up was done at 6 months to 1 year.

Endpoints

Hormonal levels
Acne
Hirsutism
Seborrhea

Results

Treatment with the combination pill resulted in stability of progesterone, significant reduction in hormonal levels and increase in SHBG.
A significant decrease by 82.8% in LH and LH/FSH ratio was seen in the 12^th treatment cycle
The pill resulted in reduction of 63.8% of androstenedione (A), 50% of total testosterone (T.Te), 70.6% of free testosterone (F. Te) and 63% of dehydroepiandrosterone sulphate (DHEAS).
Concentrations of SHBG increased by 530% in the 6^th cycle and was sustained till the end of therapy.
At the end of 12^th cycle, acne disappeared in 71.2% and 28.8% had moderate acne.
At the end of 36^th cycle, acne disappeared in 100%, seborrhea in 76.4% and hirsutism in 75%.
The total Ferryman-Gallwey score decreased from a mean of 12.2 to 7.5 after therapy, p<0.01.
There was a remarkable decrease in the mean ovarian volume at the end of therapy.

Conclusion

Treatment with the monophasic combination comprising ethinylestradiol and cyproterone acetate for 36 cycles without interruption resulted in significant improvements in the clinical hyperandrogenic symptoms in women with PCOS.

Contraception. 1990 Dec;42(6):611-9. Doi: 10.1016/0010-7824(90)90002-d.