• Contraceptive efficacy as determined by serum HCG pregnancy test (or home pregnancy test). [ Time Frame: 2 years (26 cycles) ] [ Designated as safety issue: No ]
• Drug safety as determined by [S]AE monitoring, cervical cytology, physical & gynecological exams, vital signs, and routine laboratory parameters. [ Time Frame: 2 years (26 cycles) ] [ Designated as safety issue: Yes ]
• Cycle control as determined by patient diary records. [ Time Frame: 2 years (26 cycles) ] [ Designated as safety issue: No ]

• Contraceptive efficacy as determined by serum HCG pregnancy test (or home pregnancy test). [ Time Frame: 2 years (26 cycles) ]
• Drug safety as determined by [S]AE monitoring, cervical cytology, physical & gynecological exams, vital signs, and routine laboratory parameters. [ Time Frame: 2 years (26 cycles) ]
• Cycle control as determined by patient diary records. [ Time Frame: 2 years (26 cycles) ]

The primary purpose of this study is to evaluate the effects of the NOMAC-E2 combined oral contraceptive on bone mineral density (BMD).

• Drug: NOMAC-E2
• Drug: LNG/EE

• Active Comparator: Estradiol and Nomegestrol Acetate
• Active Comparator: Levonorgestrel and Ethinyl Estradiol

Inclusion criteria:

• Sexually active women, at risk for pregnancy and not planning to use condoms during treatment;
• At least 20 but not older than 35 years of age at the time of screening;
• BMI = 17 and = 35;
• Good physical and mental health;
• Willing to give informed consent in writing;
• Willing to take part in the trial for two years.

Exclusion criteria:

• Family history of osteoporotic fracture below the age of 70;
• Postgastrectomy;
• History of eating disorder, viz. anorexia nervosa, bulimia;
• Endocrine disorder (including controlled diabetes, [para]thyroid disease, Cushing's disease);
• Rheumatoid arthritis;
• Significant scoliosis;
• Fasting parathyroid hormone (PTH) outside the reference range at screening;
• Fasting calcitonin outside the reference range at screening;
• Prolactin above the reference range (hyperprolactinemia) at screening;
• Fasting cholesterol and/or triglycerides above the reference range for age at screening (treatment with lipid lowering drugs not allowed);
• Engaging in vigorous exercise such as marathon, competitive swimming, triathlon;
• Smoking more than ten cigarettes/day;
• Use of more than two units of alcohol a day;

• Use of one or more of the following drugs:

  • gonadotropin releasing hormone (GnRH) analogues (also past use for more than six months at any time, or for any period of time less than six months ago is a contraindication);
  • systemic or inhaled administration of corticosteroids (also past use for more than one year, less than five years ago or any period of time in the past year is a contraindication);
  • thiazide diuretics;
  • thyroid hormone;
  • bisphosphonates;
  • calcium supplementation in combination with vitamin D supplementation/ calcitonin;
  • ever treatment after childhood with fluorides;
• Contraindications for contraceptive steroids
• An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia[CIN], squamous intraepithelial lesion [SIL], carcinoma in situ, invasive carcinoma) at screening;
• Clinically relevant abnormal laboratory result at screening as judged by the investigator;
• Use of an injectable hormonal method of contraception; within 6 months of an injection with a 3-month duration, within 4 months of an injection with a 2-month duration, within 2 months of an injection with a 1-month duration;
• Within 12 months after a pregnancy prior to the start of trial medication;
• Breastfeeding or within 12 months after stopping breastfeeding prior to the start of trial medication;
• Present use or use within 2 months prior to the start of the trial medication of the following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (other than pre- and post-treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St John's Wort);
• Administration of investigational drugs and/or participation in another clinical trial within 2 months prior to the start of the trial medication or during the trial period.