Uehara Mari, Wada-Hiraike Osamu, Koga Kaori, Yamamoto Naoko, Hirano Mana, Harada Miyuki, Hirota Yasushi, Osuga Yutaka
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
Endocr J. 2022 Dec 28;69(12):1437-1445. doi: 10.1507/endocrj.EJ22-0158. Epub 2022 Sep 7.
Dienogest (DNG) is widely used to treat dysmenorrhea associated with estrogen-dependent diseases such as endometriosis and adenomyosis. DNG becomes unnecessary after menopause when estrogen secretion declines drastically. However, there are no clear criteria for when to halt DNG in perimenopausal patients. Menstruation and dysmenorrhea often resume after discontinuation due to approaching menopause. This case-control study used serum estradiol and follicle-stimulating hormone (FSH) levels to predict whether menstruation would resume in perimenopausal women after discontinuation of DNG. The study enrolled patients aged ≥40 years with endometriosis and/or adenomyosis and who had either completed oral DNG therapy (DNG group) or had spontaneous menopause without hormone therapy (control group). We assessed estradiol and FSH values before DNG termination or the final menstrual period. DNG group members that resumed menstruation after DNG termination (D (+) group, n = 17) had significantly higher estradiol and lower FSH levels than those who did not (D (-) group, n = 22) up to four months before DNG termination but not from four to 12 months. Estradiol and FSH levels were not significantly different between the D (-) and control groups. Receiver operating characteristic curves created from the estradiol and FSH values indicated that menstruation resumed when levels were ≥17 pg/mL and <100 mIU/mL, respectively. In contrast, menstruation did not resume in cases of estradiol ≤20 pg/mL and FSH >80 mIU/mL. The study results provide useful criteria for deciding when to terminate DNG in perimenopausal patients that consider their tolerance for resuming menstruation. Applications to menopause-inducing therapy for uterine fibroids and other conditions are anticipated. Further large-scale studies are needed.
地诺孕素（DNG）被广泛用于治疗与雌激素依赖性疾病相关的痛经，如子宫内膜异位症和子宫腺肌病。绝经后雌激素分泌大幅下降，此时DNG不再必要。然而，对于围绝经期患者何时停用DNG尚无明确标准。由于接近绝经，停药后月经和痛经往往会恢复。本病例对照研究使用血清雌二醇和卵泡刺激素（FSH）水平来预测围绝经期妇女停用DNG后月经是否会恢复。该研究纳入了年龄≥40岁、患有子宫内膜异位症和/或子宫腺肌病、已完成口服DNG治疗的患者（DNG组）或未经激素治疗自然绝经的患者（对照组）。我们评估了DNG终止前或最后一次月经周期前的雌二醇和FSH值。DNG组中DNG终止后恢复月经的成员（D（+）组，n = 17）在DNG终止前四个月内的雌二醇水平显著高于未恢复月经的成员（D（-）组，n = 22），FSH水平则显著低于后者，但在终止后四至十二个月时无此差异。D（-）组和对照组的雌二醇和FSH水平无显著差异。根据雌二醇和FSH值绘制的受试者工作特征曲线表明，当雌二醇水平≥17 pg/mL且FSH水平<100 mIU/mL时月经恢复。相反，如果雌二醇≤20 pg/mL且FSH>80 mIU/mL，则月经不会恢复。研究结果为决定围绝经期患者何时终止DNG提供了有用的标准，该标准考虑了她们对月经恢复的耐受性。预计该标准将应用于子宫肌瘤和其他疾病的诱导绝经治疗。还需要进一步的大规模研究。
