Effects of oral lynestrenol administration on prenatal and postnatal progeny development in rabbits.

Pregnant Belted Dutch rabbits were administered lynestrenol (17-alpha-ethynyl-oestr-4-en-17-beta-ol) orally on days 6-18 of gestation at a dose of 0.5 mg/kg/day. The dose littered on term and the surviving offspring were observed until four weeks old. Neurological disturbances characterized by behavioural abnormalities and locomotor disabilities were observed. About 40% of the offspring died within four weeks, and more than 70% of these had congenital malformations.

Further investigations on the cytological effects of some contraceptives.

Anovlar induces a mitodepressive effect, producing abnormal prophases and a considerable number of micronuclei, i.e. Anovlar can produce major cytological abnormalities. On the other hand, Lyndiol induces minor abnormalities leaving the process of mitosis to proceed almost normally. Microgynon 30 did not show any effect on any of the mitotic stages. Our conclusion may offer an explanation for the contradictory results found in the literature upon the cytological effect of oral contraceptives, although the major chemical constitution of all contraceptives used is the same, still there are minor differences in their chemical structure. These minor differences in chemical structure may be the deciding cause whether or not a contraceptive is harmful.

PIP: Anovlar induces a mitodepressive effect, producing abnormal prophases and a considerable number of micronuclei, i.e., Anovlar can produce major cytological abnormalities. Conversely, Lyndiol induces minor abnormalities leaving the process of mitosis to proceed almost normally. Microgynon 30 did not show any effect on any of the mitotic stages. The conclusion may offer an explanation for the contradictory results found in the literature of the cytological effect of oral contraceptives, although the major chemical constitution of all contraceptives used is the same, still there are minor differences in their chemical structure. These minor differences may be the deciding factor as to whether or not a contraceptive is harmful.

Teratogenicity and embryotoxicity of orally administered lynestrenol in rabbits.

Pregnant Belted Dutch rabbits were administered lynestrenol 17-alpha-ethynyl-oestr-4-en-17-beta-ol) orally on days 6-18 of gestation at doses of 0.1, 0.5, and 2.5 mg/kg/day. On day 29 of gestation the does were killed and autopsied and the fetuses were examined for external, visceral and skeletal abnormalities. Lynestrenol administration produced a statistically significant increase in the number of post-implantation loss (p = 0.05) and in the average per cent of abnormal fetuses per dose group (63%, 66%, and 87% for the medicated group, versus 12% for the placebo group, p = 0.05). None of the doses tested was lethal to the does, but the average weight gain was decreased for the medium and the high dose groups. Abnormalities of the central nervous system and skeletal variants were the most frequent findings in the fetuses.

Lynoestrenol.

PIP: This monograph on lynestrenol includes chemical and physical data (synonyms and tradenames), structural and molecular formulae and molecular weight, chemical and physical properties of lynestrenol, and the production, use, occurrence, and analysis of lynestrenol. Production of lynestrenol, which is not known to occur naturally, is by treatment of 19-nortestosterone with ethane-1,2-dithiol and boron trifluoride to give the 3-thioketal, followed by oxidation steps, and concluded by treatment with lithium acetylide. Lynestrenol is used primarily as a component of contraceptive tablets. It has also been used (in combination with mestranol) to control dysfunctional uterine bleeding and endometriosis. Typical analytical methods for determining lynestrenol as a bulk chemical are presented tabularly. Biological data relevant to the evaluation of carcinogenic risk to humans are also presented in brief. Lynestrenol has been tested in mice and rats by oral administration either alone or in combination with mestranol. No increases in any tumor incidences were found. No case reports or human epidemiological studies on lynestrenol alone are available. It is therefore not possible to evaluate this agent's possible carcinogenicity, although as an agent in oral contraceptives it is implicated in their side effects.^ieng

Studies in mice on the mutagenicity of two contraceptive drugs.

An experiment is described which tests for visible and invisible mutants in mice treated with four different doses each of the contraceptives Gynanovlar and Lyndiol. The results show that there is no reason to suppose that either substance has an appreciable mutagenic effect, expressed as an increase of antenatal and postnatal lethals or visibles. The substrain CBA/CagCam, used throughout, has an incidence of 0.27% of singly occurring abnormalities, mainly of the appendicular skeleton, which distinguishes it from the parent CBA strain and its axial variation described by Gruneberg (1963).