|Oettel M et al.|
The Progestin-Only-Pill (POP) is not a Niche Option: New Preclinical and Clinical Data about the Interrelations between Levonorgestrel-Dosage, Peripheral as well as Central Contraceptive Effects and Bleeding Behavior
Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2015; 12 (4): 246-250
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Keywords: bleeding behavior, contraception, dose-relationship, Levonorgestrel, Progestin-only pill
In preclinical studies with levonorgestrel (LNG) in rabbits and rats, we found that the pre-ovulatory as well as the post-ovulatory administration show no or only limited contraceptive activity. Therefore, the design of a progestin-only-oral contraceptive (POP) only on the base of non-ovulatory effects must be leading to sub-optimal results. On the other hand, elevation the dose above the ovulation-inhibition level can cause bleeding disturbances. As a contribution for better clarifying these problems, a clinical proof-of-concept-study in a randomized, open-label, parallel group design was undertaken. The 20 volunteers included cyclic women that were divided in two groups. In group A (n = 10) the volunteers received daily 0.06 mg LNG over 56 days and in group B (n = 10) daily 0.09 mg LNG also over 56 days. The efficacy parameters were changes in progesterone plasma levels, urine pregnancy tests, behavior of cervical mucus, bleeding pattern and additionally evaluation of some parameters for safety and tolerability. The results show that in the 0.06 mg group 3 of 10 women ovulated (plasma progesterone-monitoring) whereas in the 0.09 mg group none of the volunteers ovulated during the 20 treatment cycles. In no case, the urine pregnancy tests were positive. The investigation of the cervical mucus show consistently a score < 10, which was considered as “poor” or “unfavourable” for sperm penetration in either treatment arms. The bleeding pattern during the higher LNG-dosage treatment were better than in the lower dosage group (mean 1.6% bleeding days during 0.09 mg LNG vs. 3.6% in the 0.06 mg group). All the bleeding irregularities occurred only in the first month of treatment period. Tolerability and safety were satisfying in both groups. These promising results must be confirmed in a suitable larger clinical study.