To investigate the sequential approach to oral contraception, 509 fertile subjects were given 0.08 mg of mestranol daily for 14 days beginning on the fifth cycle day, followed by 0.08 mg of mestranol with 2 mg of norethindrone for six days. One pregnancy due to method failure occurred in 6,212 cycles of therapy. Thirty-seven patients reported amenorrhea in 57 cycles. Spotting or breakthrough bleeding or both occurred in 254 cycles. The majority of 88 incidences of gastrointestinal disturbance were evident in the first three cycles of therapy. Other side effects included weight changes, headache, leg pain, backache, and edema. Therapy was discontinued in 101 cases—in 24 of these for drug-related reasons. It was concluded that mestranol-norethindrone sequential medication provides an additional effective method of oral contraception.
Tyler ET, Matsner EM, Gotlib M, Levin M, Tucker JS, Parrott FM. Oral Contraception by the Sequential Approach. JAMA. 1966;197(12):943–948. doi:10.1001/jama.1966.03110120049012
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