Wadsworth P F, Heywood R, Allen D G, Hossack D J, Sortwell R J, Walton R M
Contraception. 1979 Oct;20(4):339-51. doi: 10.1016/s0010-7824(79)80044-x.
The effects of both progesterone- and norethisterone-loaded intravaginal rings were investigated in twenty-five rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either the human dosage level of the hormone or ten times this level. Untreated placebo rings were used for control purposes. The devices were well retained. With the exception of increased plasma fibrinogen levels in animals treated with norethisterone, no marked differences in either local or systemic toxicity between the progesterone and norethisterone intravaginal rings were apparent. Following insertion of the hormone-treated intravaginal rings, a dose-related decrease in vaginal bleeding was recorded. The vaginal microbial flora were assessed qualitatively and semiquantitatively and all groups including the placebo controls showed a changes in mcirobial populations. Terminal studies indicated that at high dose levels, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular endometrial epithelium had occurred. An increase in cervical mucus was observed within the lumen of the endocervical canal in a proportion of hormone-treated animals. In the vagina, a dose-related focal or diffuse atrophy of the mucosal epithelium was found.
在25只恒河猴身上研究了含孕酮和炔诺酮的阴道环的效果，为期52周。阴道环的设计目的是实现激素的人体剂量水平或该剂量水平10倍的持续释放。使用未处理的安慰剂环作为对照。这些装置保留良好。除了接受炔诺酮治疗的动物血浆纤维蛋白原水平升高外，孕酮和炔诺酮阴道环在局部或全身毒性方面没有明显差异。插入激素处理过的阴道环后，记录到阴道出血呈剂量相关减少。对阴道微生物菌群进行了定性和半定量评估，所有组包括安慰剂对照组的微生物种群均有变化。终末研究表明，在高剂量水平下，排卵受到抑制，子宫黏膜和腺性子宫内膜上皮出现广泛萎缩。在一部分接受激素治疗的动物的子宫颈管腔内观察到宫颈黏液增多。在阴道中，发现黏膜上皮出现剂量相关的局灶性或弥漫性萎缩。
