Downs Jodi L, Urbanski Henryk F
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006, USA.
Biol Reprod. 2006 Oct;75(4):539-46. doi: 10.1095/biolreprod.106.051839. Epub 2006 Jul 12.
Femalerhesus macaques show monthly menstrual cycles and eventually enter menopause at approximately 25 yr of age. To help identify early biomarkers of menopause in this nonhuman primate, we monitored reproductive hormones longitudinally from aged female macaques during the transitions from premenopause to perimenopause and postmenopause and found that, indeed, elevated plasma FSH was a better predictive factor of menopause onset than age. In a second experiment, we compared reproductive hormone profiles of young adult macaques (8-10 yr old) with those of regularly cycling old macaques (approximately 24 yr old). Indwelling vascular catheters were used for remote blood collection for at least 100 consecutive days, thereby covering three complete menstrual cycles in each macaque. Plasma levels of estradiol, progesterone, LH, FSH, follicular phase inhibin B, and anti-müllerian hormone (AMH) were determined during each menstrual cycle and were averaged for each animal; group mean differences were analyzed using one-way ANOVA. Old premenopausal macaques showed regular menstrual cycles that were qualitatively indistinguishable from those of young macaques; peak plasma levels of estradiol, progesterone, and LH were not significantly different. In marked contrast, peak plasma FSH concentrations were significantly higher, while inhibin B and AMH levels were generally lower, in the old premenopausal macaques compared with those in the young macaques. These data provide further evidence that rhesus macaques serve as an excellent model to study underlying mechanisms of human menopause. Furthermore, the data suggest that an age-related change in FSH, inhibin B, and AMH secretion may be the first endocrine manifestation of the transition into perimenopause, potentially having value in predicting the onset of the perimenopausal transition.
雌性恒河猴表现出每月一次的月经周期，并最终在大约25岁时进入更年期。为了帮助识别这种非人类灵长类动物更年期的早期生物标志物，我们在老年雌性恒河猴从绝经前过渡到围绝经期和绝经后的过程中纵向监测生殖激素，发现血浆促卵泡激素（FSH）升高确实比年龄更能预测更年期的开始。在第二项实验中，我们比较了年轻成年恒河猴（8 - 10岁）和正常月经周期的老年恒河猴（约24岁）的生殖激素谱。使用留置血管导管进行至少连续100天的远程采血，从而覆盖每只恒河猴的三个完整月经周期。在每个月经周期中测定雌二醇、孕酮、促黄体生成素（LH）、FSH、卵泡期抑制素B和抗苗勒管激素（AMH）的血浆水平，并对每只动物的水平进行平均；使用单因素方差分析分析组间平均差异。绝经前的老年恒河猴表现出与年轻恒河猴在质量上无法区分的规律月经周期；雌二醇、孕酮和LH的血浆峰值水平没有显著差异。与之形成鲜明对比的是，与年轻恒河猴相比，绝经前老年恒河猴的血浆FSH峰值浓度显著更高，而抑制素B和AMH水平通常更低。这些数据进一步证明恒河猴是研究人类更年期潜在机制的优秀模型。此外，数据表明FSH、抑制素B和AMH分泌的年龄相关变化可能是进入围绝经期过渡的首个内分泌表现，可能对预测围绝经期过渡的开始具有价值。
