This is a Phase 2, dose-finding, cross-over study for the purposes of evaluating the effect of a NES/E2 transdermal gel delivery on ovulation suppression in normal ovulating women.

Inclusion Criteria:

• Woman is between 18 and 40 years of age
• Has intact uterus and ovaries
• Has regular menstrual cycles of 25-35 days duration
• Able to comply with the protocol, including frequent blood sampling, and lives within the catchment area of the clinic
• Understands the study procedures and agrees to participate in the study by giving written informed consent
• Able to use non-hormonal, double-barrier contraceptives (e.g. condoms and diaphragm) with every act of intercourse, or has been sterilized with tubal ligation, or only male partner has been sterilized with vasectomy
• Progesterone >10 nmol/L in at least one sample in the lead-in cycle

Exclusion Criteria:

• All contraindications to OC use including
• Thrombophlebitis or thromboembolic disorders
• Past history of deep vein thrombophlebitis or thromboembolic disorders
• Past or current cerebrovascular or coronary artery disease
• Known or suspected carcinoma of the breast
• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
• Undiagnosed abnormal genital bleeding
• Cholestatic jaundice of pregnancy or jaundice with prior pill use
• Hepatic adenomas or carcinomas
• Woman has a history of headaches with focal neurological symptoms
• Known or suspected pregnancy
• Aged >35 and smoker
• BMI >29
• Positive urine pregnancy test at the screening or baseline visit
• Desired pregnancy within the duration of the study
• Known hypersensitivity to progestins
• Known hypersensitivity to estrogen
• Undiagnosed vaginal discharge or vaginal lesions or abnormalities
• In accordance with the Bethesda system of classification Women with a current abnormal Pap smear suggestive of high-grade pre cancerous lesion(s), including HGSIL, are excluded
• Women with LGSIL or ASCUS/high-risk HPV positive may participate if further evaluated with colposcopy and biopsy and no evidence of a lesion with a severity >CIN I is present and/or endocervical curettage is negative
• Women with a biopsy finding of CIN I should have follow up for this finding per standard of care; women are excluded if treatment is indicated In accordance with other Pap class systems
• Women with high grade dysplasia are excluded
• Women with low grade dysplasia or CIN I interpretation on Pap smear may participate based on investigator discretion in accordance with local standard of care
• Breastfeeding
• Cancer (past history of any carcinoma or sarcoma)
• History of a significant psychiatric disorder, including severe depression.
• Chronic or acute liver or renal disease
• Hypertension-- controlled by medication or defined by diastolic BP 85 mm Hg or systolic BP 135mm Hg after 15 minutes rest
• Dermatitis, psoriasis or other severe skin disorder
• Known or suspected alcoholism or drug abuse
• Clinically significant abnormalities of laboratory safety tests
• Chronic disease or history of illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject
• Woman is participating or has participated in another clinical study (involving an investigational drug) within one month prior to enrollment.
• Use of injectable contraceptives during the previous 3 months (e.g. cyclofem) or 9 months (e.g. DMPA)
• Use of oral contraceptives within the past 1 month
• Use of concomitant drugs that may interact with the study drugs