Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
Hum Reprod. 2010 Feb;25(2):360-7. doi: 10.1093/humrep/dep424. Epub 2009 Dec 4.
Prostaglandins produced via cyclooxygenase-2 (COX-2) within the periovulatory follicle are required for successful ovulation. Inhibition of follicular prostaglandin synthesis prevents timely follicle rupture and oocyte release. This study was conducted to determine if a 5-day course of oral administration of the COX-2 inhibitor meloxicam can prevent ovulation while maintaining normal menstrual cycles in non-human primates.
Adult female cynomolgus monkeys were studied in each of four sequential menstrual cycles. In Cycle 1, a serum sample was obtained each day and assayed for estradiol, progesterone and luteinizing hormone; first menses was also noted to establish parameters of a normal menstrual cycle for each animal. In Cycle 2, meloxicam was administered orally once each day for 5 days beginning at either mid follicular (n = 4), late follicular (n = 4) or periovulatory (n = 4) phase of the menstrual cycle; daily serum samples and menses were assessed as for Cycle 1. In Cycle 3, the follicle-bearing ovary was removed 2 days after the expected day of ovulation (n = 3-4/treatment group). In Cycle 4, monkeys received the 5-day courses of oral meloxicam as in Cycle 2 (n = 3-4/treatment group), and the remaining ovary was removed. Ovaries were examined for the presence of an oocyte within the follicle.
Monkeys had the expected levels of changing reproductive hormones during Cycle 1. Meloxicam treatment in Cycle 2 did not alter hormone levels or the luteal phase length. Follicles of ovaries removed during Cycle 3 did not contain oocytes, indicating successful ovulation. Follicles did contain oocytes after meloxicam treatment beginning in the mid follicular (67%), late follicular (100%) or periovulatory (50%) phase of Cycle 4, indicating failure of ovulation.
A 5-day course of oral meloxicam administered around the time of ovulation reduced the rate of oocyte release without alteration of reproductive hormones or menstrual cycle length. Meloxicam may be effective as an emergency contraceptive in women.
排卵过程中卵泡内环氧化酶 2（COX-2）产生的前列腺素对于成功排卵是必需的。抑制卵泡内前列腺素的合成会阻止卵泡及时破裂和卵子释放。本研究旨在确定在非人类灵长类动物中，5 天口服 COX-2 抑制剂美洛昔康能否预防排卵，同时维持正常月经周期。
在四个连续的月经周期中，对成年雌性食蟹猴进行了研究。在周期 1 中，每天采集一份血清样本，检测雌二醇、孕酮和促黄体生成素；还记录了第一次月经，以确定每个动物的正常月经周期参数。在周期 2 中，美洛昔康每天口服一次，共 5 天，开始于月经周期的中卵泡期（n=4）、晚卵泡期（n=4）或排卵前期（n=4）；每日血清样本和月经情况与周期 1 相同。在周期 3 中，在预计排卵后第 2 天切除有卵泡的卵巢（n=3-4/治疗组）。在周期 4 中，猴子接受了与周期 2 相同的 5 天口服美洛昔康疗程（n=3-4/治疗组），并切除了剩余的卵巢。检查卵巢中卵泡内是否有卵子。
猴子在周期 1 中具有预期的生殖激素变化水平。周期 2 中美洛昔康治疗并未改变激素水平或黄体期长度。周期 3 中切除的卵巢卵泡中没有卵子，表明排卵成功。在周期 4 中，美洛昔康从中卵泡期（67%）、晚卵泡期（100%）或排卵前期（50%）开始治疗后，卵泡中仍含有卵子，表明排卵失败。
排卵前后 5 天口服美洛昔康可降低卵子释放率，而不改变生殖激素或月经周期长度。美洛昔康可能是一种有效的女性紧急避孕药。
