Contraceptive Pill and Hormonal Vaginal Ring in Women With Polycystic Ovary Syndrome - Full Text View

Purpose

The main aims of this study are:

to investigate and compare the effects of long lasting use (59 weeks) of vaginal and oral contraceptives on androgen secretion, insulin and glucose metabolism, lipid profile, and serum levels of SHBG and hs-CRP in women with PCOS.
to compare the metabolic effects of oral and vaginal combined contraceptives and to find out whether oral or transvaginal contraceptive can be recommended to a particular group of women, for example in women with increased metabolic risks.
to clarify whether the unfavourable effects of combined contraceptives diminish with time (after use of one year).

Condition	Intervention	Phase
Adverse Effect of Oral Contraceptives, Sequela	Drug: oc:E-E-desogestrel/vaginal ring:E-E -ethonogestrel	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Effects of Contraceptive Pill and Hormonal Vaginal Ring on Hormonal, Inflammatory and Metabolic Parameters in Women of Reproductive Age With Polycystic Ovary Syndrome (PCOS).

Resource links provided by NLM:

MedlinePlus related topics: Polycystic Ovary Syndrome

Drug Information available for: Desogestrel

U.S. FDA Resources

Further study details as provided by University of Oulu:

Primary Outcome Measures:

Change in Matsuda index during the oral contraceptive pill (E-E-desogestrel)/vaginal ring (E-E -ethonogestrel) [ Time Frame: Change from baseline in Matsuda index at 59 weeks of treament ] [ Designated as safety issue: No ]
Calculation of the Matsuda index according to the following equation: [10000 / √((fasting glucose x fasting insulin)x (Gmeanogtt x Imeanogtt))]

Secondary Outcome Measures:

Change in high sensitive C-reactive protein (mg/l) during the oral contraceptive pill (E-E-desogestrel)/vaginal ring (E-E -ethonogestrel) [ Time Frame: Change from baseline in serum CRP concentrations at 59 weeks of treament ] [ Designated as safety issue: No ]
Change in Free Androgen Index during the oral contraceptive pill (E-E-desogestrel)/vaginal ring (E-E -ethonogestrel) [ Time Frame: Change from baseline in Free Androgen Index at 59 weeks of treament ] [ Designated as safety issue: No ]
Calculation by using the equation 100×T (nmol/l)/SHBG (nmol/l).

Estimated Enrollment:	42
Study Start Date:	April 2012
Estimated Study Completion Date:	December 2019
Estimated Primary Completion Date:	December 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Oral contraceptive pill	Drug: oc:E-E-desogestrel/vaginal ring:E-E -ethonogestrel The OC or vaginal ring will be used in 9 weeks periods followed by one week's break each. After a wash-out period of at least 2 months of any previous hormonal contraceptives all examinations will be performed at the 1st to 5th day of the menstruation cycle at baseline and then at the 9th, 29th and 59th week and the last 1 month after stopping contraception. Blood samples will be collected between 07 and 10 AM after an overnight fast and during the follicular phase or at any time in cases of amenorrhea. After centrifugation serum is filled in eight tubes with at least 2 ml of serum in each, and immediately frozen at -70ºC as well as one tube of plasma. Every tube will be marked appropriately. Fasting plasma glucose and HbA1c will be analysed at once at every appointment. Other Name: Mercilon, Nuva-Ring
Active Comparator: Contraceptive ring	Drug: oc:E-E-desogestrel/vaginal ring:E-E -ethonogestrel The OC or vaginal ring will be used in 9 weeks periods followed by one week's break each. After a wash-out period of at least 2 months of any previous hormonal contraceptives all examinations will be performed at the 1st to 5th day of the menstruation cycle at baseline and then at the 9th, 29th and 59th week and the last 1 month after stopping contraception. Blood samples will be collected between 07 and 10 AM after an overnight fast and during the follicular phase or at any time in cases of amenorrhea. After centrifugation serum is filled in eight tubes with at least 2 ml of serum in each, and immediately frozen at -70ºC as well as one tube of plasma. Every tube will be marked appropriately. Fasting plasma glucose and HbA1c will be analysed at once at every appointment. Other Name: Mercilon, Nuva-Ring

Arms

Assigned Interventions

Active Comparator: Oral contraceptive pill

Drug: oc:E-E-desogestrel/vaginal ring:E-E -ethonogestrel

The OC or vaginal ring will be used in 9 weeks periods followed by one week's break each.

After a wash-out period of at least 2 months of any previous hormonal contraceptives all examinations will be performed at the 1st to 5th day of the menstruation cycle at baseline and then at the 9th, 29th and 59th week and the last 1 month after stopping contraception.

Blood samples will be collected between 07 and 10 AM after an overnight fast and during the follicular phase or at any time in cases of amenorrhea. After centrifugation serum is filled in eight tubes with at least 2 ml of serum in each, and immediately frozen at -70ºC as well as one tube of plasma. Every tube will be marked appropriately. Fasting plasma glucose and HbA1c will be analysed at once at every appointment.

Other Name: Mercilon, Nuva-Ring

Active Comparator: Contraceptive ring

Drug: oc:E-E-desogestrel/vaginal ring:E-E -ethonogestrel

The OC or vaginal ring will be used in 9 weeks periods followed by one week's break each.

After a wash-out period of at least 2 months of any previous hormonal contraceptives all examinations will be performed at the 1st to 5th day of the menstruation cycle at baseline and then at the 9th, 29th and 59th week and the last 1 month after stopping contraception.

Blood samples will be collected between 07 and 10 AM after an overnight fast and during the follicular phase or at any time in cases of amenorrhea. After centrifugation serum is filled in eight tubes with at least 2 ml of serum in each, and immediately frozen at -70ºC as well as one tube of plasma. Every tube will be marked appropriately. Fasting plasma glucose and HbA1c will be analysed at once at every appointment.

Other Name: Mercilon, Nuva-Ring

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

women aged between 18 to 40 years
diagnosed PCOS (Rotterdam criteria)
healthy, no medications
no use of hormonal contraceptives or wash-out period of at least two months
no contraindications to hormonal contraception

Exclusion Criteria:

regular smoking
excessive alcohol use
pregnancy or breastfeeding
oversensitivity to active ingredients
migraine with focal aura
severe or multiple risk factors to thrombosis
diagnosed or suspected cancer
diagnosed or suspected estrogen-dependent tumor
acute or chronic hepatocellular disease -related abnormal liver function
hepatic adenomas or carcinomas
undiagnosed abnormal vaginal bleeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01588873

Contacts

Contact: Laure C Morin-Papunen, PhD

+358 8 3154109

lmp@cc.oulu.fi

Locations

Finland
Department of Obstetrics and Gynaecology, University Hospital of Oulu	Recruiting
Oulu, Finland, 90029
Contact: Laure C Morin-Papunen, PhD +358 8 3154109 lmp@cc.oulu.fi
Contact: Juha S Tapanainen, PhD +358 8 3153172 juha.tapanainen@oulu.fi
Principal Investigator: Anni S Rantala, med student
Sub-Investigator: Johanna Puurunen, MD

Sponsors and Collaborators

University of Oulu

Investigators

Principal Investigator:

Laure C Morin-Papunen

University of Oulu

More Information

Publications:

Acién P, Mauri M, Gutierrez M. Clinical and hormonal effects of the combination gonadotrophin-releasing hormone agonist plus oral contraceptive pills containing ethinyl-oestradiol (EE) and cyproterone acetate (CPA) versus the EE-CPA pill alone on polycystic ovarian disease-related hyperandrogenisms. Hum Reprod. 1997 Mar;12(3):423-9.

Allen HF, Mazzoni C, Heptulla RA, Murray MA, Miller N, Koenigs L, Reiter EO. Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2005 Aug;18(8):761-8.

Armstrong VL, Wiggam MI, Ennis CN, Sheridan B, Traub AI, Atkinson AB, Bell PM. Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyl oestradiol/cyproterone acetate. QJM. 2001 Jan;94(1):31-7.

Ball MJ, Ashwell E, Jackson M, Gillmer MD. Comparison of two triphasic contraceptives with different progestogens: effects on metabolism and coagulation proteins. Contraception. 1990 Apr;41(4):363-76.

Bilgir O, Kebapcilar L, Taner C, Bilgir F, Kebapcilar A, Bozkaya G, Yildiz Y, Yuksel A, Sari I. The effect of ethinylestradiol (EE)/cyproterone acetate (CA) and EE/CA plus metformin treatment on adhesion molecules in cases with polycystic ovary syndrome (PCOS). Intern Med. 2009;48(14):1193-9. Epub 2009 Jul 15.

Cagnacci A, Paoletti AM, Renzi A, Orrù M, Pilloni M, Melis GB, Volpe A. Glucose metabolism and insulin resistance in women with polycystic ovary syndrome during therapy with oral contraceptives containing cyproterone acetate or desogestrel. J Clin Endocrinol Metab. 2003 Aug;88(8):3621-5.

Carranza-Lira S, Magaña-Padilla NR. [Ultrasonographic and lipid changes in polycystic ovary syndrome according to the type of treatment ]. Ginecol Obstet Mex. 2002 Jun;70:285-8. Spanish.

Charitidou C, Farmakiotis D, Zournatzi V, Pidonia I, Pegiou T, Karamanis N, Hatzistilianou M, Katsikis I, Panidis D. The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome. Atherosclerosis. 2008 Feb;196(2):958-65. Epub 2007 Apr 6.

Chasan-Taber L, Willett WC, Stampfer MJ, Hunter DJ, Colditz GA, Spiegelman D, Manson JE. A prospective study of oral contraceptives and NIDDM among U.S. women. Diabetes Care. 1997 Mar;20(3):330-5.

Chen MJ, Yang WS, Chen HF, Kuo JJ, Ho HN, Yang YS, Chen SU. Increased follistatin levels after oral contraceptive treatment in obese and non-obese women with polycystic ovary syndrome. Hum Reprod. 2010 Mar;25(3):779-85. Epub 2010 Jan 20.

Cibula D, Sindelka G, Hill M, Fanta M, Skrha J, Zivny J. Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin. Hum Reprod. 2002 Jan;17(1):76-82.

Cibula D, Fanta M, Vrbikova J, Stanicka S, Dvorakova K, Hill M, Skrha J, Zivny J, Skrenkova J. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. Hum Reprod. 2005 Jan;20(1):180-4. Epub 2004 Dec 2.

Costello MF, Shrestha B, Eden J, Johnson NP, Sjoblom P. Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review. Hum Reprod. 2007 May;22(5):1200-9. Epub 2007 Jan 29. Review.

Creatsas G, Koliopoulos C, Mastorakos G. Combined oral contraceptive treatment of adolescent girls with polycystic ovary syndrome. Lipid profile. Ann N Y Acad Sci. 2000;900:245-52.

Duleba AJ, Banaszewska B, Spaczynski RZ, Pawelczyk L. Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. Fertil Steril. 2006 Apr;85(4):996-1001. Epub 2006 Mar 9.

Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74.

Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005 Mar 24;352(12):1223-36. Review. No abstract available.

Responsible Party:	University of Oulu
ClinicalTrials.gov Identifier:	NCT01588873 History of Changes
Other Study ID Numbers:	106/2011
Study First Received:	March 28, 2012
Last Updated:	May 3, 2012
Health Authority:	Finland: Ethics Committee

Keywords provided by University of Oulu:

Oral contraceptive pill
Hormonal contraceptive ring
Polycystic ovary syndrome

Additional relevant MeSH terms:

Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Contraceptive Agents
Desogestrel

Contraceptives, Oral
Contraceptives, Oral, Combined
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptives, Oral, Synthetic

ClinicalTrials.gov processed this record on May 23, 2013