Clinical trial NCT01852786: The Effect of Hormonal Contraception on Female
Official title: Metabolic, Androgen, Blood Coagulation Parameters and Female Sexual Function in Relation to Oral Contraceptive Use and Androgen Receptor Polymorphisms in Healthy Lithuanian Women
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Adverse Effect of Oral Contraceptives, Initial Encounter
Keywords: Contraception
Hyperandrogenism
Female sexual function
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
First posted: 2013-05-14
Enrollment: 340
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 340 healthy Lithuanian women age 18- 40 years with regular menstruale cycle (22- 35 days) presenting for routine gynecologic concern or contraception purposes.

Brief summary: The aim- To evaluate the impact of combined oral contraceptives on women's psychosexual, metabolic, blood coagulation, hormonal and genetic measures.

Combined oral contraceptives (COCs) is still the most popular contraception method. It is possible to find a number of publications about their non-contraceptive benefits, also about their adverse events. Most researches are conducted during clinical trials, which are commissioned by pharmaceutical companies, in order to compare COCs of different composition. This study set out to assess the role of psychosexual, metabolic, endocrine, hormonal and genetic measures of low dose combined oral contraceptive users- 20 micrograms of Ethinylestradiol/3 mg of Drospirenone and 20 micrograms of Ethinylestradiol/75 micrograms of Gestoden. Because this study is not commercial, it is expected to obtain valuable objective data - there are very few comparative studies about the impact of COCs to woman's organism.

Detailed description: The aim

To evaluate the impact of combined oral contraceptives on women's psychosexual, metabolic, blood coagulation, hormonal and genetic measures.

The objectives

1. To asses the relation of AR polymorphisms to metabolic, androgen, blood coagulation parameters and sexual function in hormonal contraceptive users.
2. To compare the changes of metabolic, coagulation and endocrine parameters between hormonal and non-hormonal contraceptive users.
3. To assess the impact of COCs on the quality of woman's sexual life and her psychological state.
4. To assess the correlation between sex hormones and women's metabolic, endocrine, psychological, sexual function.
5. To evaluate the influence of COCs on the blood coagulation parameters.
6. To determine the importance of androgen parameters in diagnosis of hyperandrogenism.

Materials and Methods Setting׃ The study will be conducted in Lithuanian University of Health Sciences during the period from 2013 to 2016 years.

4 visits will be proceeded during the study: the screening visit and 3 additional visits - an inclusion in the study visit, a visit after 3 months and a visit after 6 months.

The screening visit (0 visit)

During the screening visit women will be questioned during the routine life and medical history. They will undergo a routine general clinical and gynecological examination:

1. height/weight (for BMI calculation) and hip/waist measurements;
2. blood pressure (BP) measurement ant a cardiac auscultation (for heart rate (HR) testing);
3. auscultation of lungs and palpation of the abdomen;
4. assessment of possible veins varicose in the legs;
5. bimanual gynecological examination;
6. breasts palpation;
7. genital ultrasound examination to assess possible anatomical anomalies;
8. thyroid ultrasound examination. Women meeting the assessment criteria will be introduced with The Informed Consent Form. Women who signed The Informed Consent Form will be invited to come for the 1 visit.

   1. visit

Women will repeatedly undergo a routine general examination (BP, HR). Genital and thyroid ultrasound will be performed.

Visual methods to determine the degree of hirsutism, as originally described by Ferriman and Gallwey (F-G), will be performed. The density of terminal hairs at 9 different body sites will be scored from 0 to 4, and total score will be calculated. In addition to the F-G scoring, the height/weight \& hip/waist measurements, will be recorded. Hirsutism will be diagnosed in case of F-G≥8 scores.

* The women, presenting for hormonal contraception use and with no contraindications for hormonal therapy, one of the two medicines registered in Lithuania will be administered׃ Daylette (20 micrograms of Ethinylestradiol and 3 mg of Drospirenone) or Lindynette (20 micrograms of Ethinylestradiol and 75 micrograms of Gestoden).
* The women, presenting for non-hormonal contraception use, will be recommended barrier copntraception use(BCM),or Natural family planing methods (NFPM).

Women will be given to fill in six questionnaires׃

1. General questionnaire, developed by the authors to find out sociodemographic status;
2. Anxiety and Depression Scale (HAD)- to determine the level of anxiety and depression;
3. WHO-Five Wellbeing Index (WHO- 5)- to evaluate woman's well being;
4. Big Five- to assess personality traits;
5. Female Sexual Function Index (FSFI)- to find out the details of their sexual life;
6. Dyadic Adjustment Scale (DAD)- to assess the compatibility of the sexual partners.

Following blood tests will be performed׃

1. Lipogram, glycemia;
2. Hormonal analyses by radioimmunoassay method ׃ total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAs), thyrotropin hormone (TSH), free thyroxine (FT4);
3. Blood coagulation test׃ clotting time according to Ovran, fibrinogen,activated partial thromboplastin time (aPTT).
4. Total blood picture test;
5. Androgen receptor (AR) polymorphism test. Patients will be invited to come for another visit after 3 months. 2 visit

Women, arriving after 3 months, will be interwied about the changes in well-being and the potential side effects caused by the COCs. Women will undergo a routine general examination BP, HR, height/weight \& hip/waist measurements). Genital and thyroid ultrasound will be performed. The signs of hyperandrogenism will be assessed using F-G scoring system.

Women will be given to fill in six questionnaires׃

1. Anxiety and Depression Scale;
2. WHO-Five Wellbeing Index;
3. Big Five;
4. Female Sexual Function Index;
5. Dyadic Adjustment Scale;
6. Satisfaction Questionnaire- to assess side effects, caused by used contraceptive method.

Patients will be invited to come for another visit after 6 months. 3 visit Women, arriving after 6 months, will be interwied about the changes in well-being and the potential side effects caused by the COCs. Women will undergo a routine general examination BP, HR, height/weight \& hip/waist measurements). The signs of hyperandrogenism will be assessed using F-G scoring system.

Women will be given to fill in six questionnaires׃

1. Anxiety and Depression Scale;
2. WHO-Five Wellbeing Index;
3. Big Five;
4. Female Sexual Function Index;
5. Dyadic Adjustment Scale;
6. Satisfaction Questionnaire. Following blood tests will be performed׃

1. Lipogram, glycemia; 2. Hormonal analyses by radioimmunoassay method ׃ T, FT, SHBG, DHEAs, TSH, FT4; 3. Blood coagulation tests׃ clotting time according to Ovran, fibrinogen, aPTT; 4. Total blood picture test.

For further use of COCs patients will consult with the gynecologist performing the study.

Eligibility criteria: Inclusion Criteria:

1. 18 - 40 years old women applying to obstetrician-gynaecologist for contraception use or for preventive health care and giving their consent to participate in the study (who signed The Informed Consent Form) will be eligible to participate in the study. It is important to note that these women should not have underlying medical conditions (chronic non - infection diseases, chronic or acute infection diseases).
2. Not using hormonal contraception for 6 months or more.

Exclusion Criteria:

1. Women applying for obstetrician-gynaecologist consultation on gynaecological pathology.
2. Women with underlying medical conditions (chronic non - infection diseases, chronic or acute infection diseases).
3. Women, planning to get pregnant during the 12 months.
4. Pregnant women (suspected or confirmed pregnancy).

Primary outcomes:
measure: Hirsutism
timeFrame: 2 years
Secondary outcomes:
measure: Blood coagulation parameters and hormonal contraception
timeFrame: 3 years
measure: Lipids concentration
timeFrame: 3 years
measure: Homeostasis model assessment
timeFrame: 3 years
measure: Free androgen Index
timeFrame: 3 years
Other outcomes:
measure: Sexual function and hormonal contraception
timeFrame: 3 years
measure: Androgen receptor polymorphism and hormonal contraception
timeFrame: 3 years
measure: AR gene polymorphism and metabolic function.
timeFrame: 3 yeras
measure: AR gene polymorphism and endocrine function
timeFrame: 3 years
measure: AR gene polymorphism and blood coagulation parameters
timeFrame: 3 years
measure: AR gene polymorphism and psychosexual function
timeFrame: 3 years
Locations:
city: Kaunas
country: Lithuania
facility: Lithuanian University of Health Sciences
Study officials:
affiliation: Lithuanian University of Health Sciences, Institute of Endocrinology
name: Birute Zilaitiene, Ass. Proff.
role: PRINCIPAL_INVESTIGATOR
References: