Opinion Endometriosis (EMS) is a common estrogen-dependent gynecological disorder, which affects quality of life and fertility of productive-aged women [1]. Current treatment of EMS is mainly based on surgery and post-operative...
moreOpinion Endometriosis (EMS) is a common estrogen-dependent gynecological disorder, which affects quality of life and fertility of productive-aged women [1]. Current treatment of EMS is mainly based on surgery and post-operative maintenance treatment of ovarian suppressive agents. A major challenge for women with EMS is the post-operative recurrence [2-3]. Some medical treatments have been suggested for EMS, such as oral contraceptive pills, and gonadotropin-releasing hormone agonists (GnRH-a). GnRH-a is an important treatment modality for EMS, significantly reducing EMS-related symptoms [4-6]. However, the employment of GnRH-a could reduce the estrogen level, leading to severe peri-menopausal symptoms such as hot flash, colpoxerosis, sexual hypoactivity, and bone loss, which hinders its long-term and extensive application [7]. The peri-menopausal symptoms could be solved by the hormone based "add-back therapy" [8-10]. As for add-back therapy, three regimens were recommended by Obstetrics and Gynecology Branch of Chinese Medical Association [11]. Estrogen and progesterone regimen: continuous combination of estrogen and progesterone. Estradiol valerate 0.5-1.5mg/d, or conjugated estrogen0.3~0.45mg/d or estradiol patch releasing 25~50μg daily, or estradiol gel 1.25g/d via percutaneous daub; for progesterone, 5mg/d dydrogesterone or 2~4mg/d medroxyprogesterone is often used. Compound preparation estradiol spironolone tablets can also be used, 1 tablet per day. Single progesterone: 1.25~2.5mg norethindrone acetate daily. Continuous use of tibolone, 1.25~2.5mg/d is recommended. According to the conventional understanding, the purpose of add-back to GnRH-a is to supplement estrogen to alleviate the series of problems caused by low estrogen. So why should we discuss this single progesterone regimen (In fact, this regimen has not been used too much clinically)? Many clinical teachers have asked this question in the gynecologic endocrine conference, this was a brief state of my personal understanding. Before answering this question, let me briefly review the mechanism of add-back therapy to GnRH-a administration. The use of GnRH-a, which will inhibit the gonadal axis, is bound to result in patients' low estrogen status. In order to alleviate the series of problems caused by this low estrogen status, meanwhile to prolong patients' GnRH-a application time and compliance, based on the theory of "estrogen dosage window" (Different tissues have different sensitivity to estrogen), some scholars put forward a therapeutic regimen (Add-back) to keep estrogen at a normal level in the body so that it will not stimulate ectopic endometrial growth without causing perimenopausal symptoms and bone loss [E2:146~183 pmol/L (40~50 pg/ml)]. Such estrogen level does not affect curative effect and can reduce side effects [12]. Since it is to solve the problem of low estrogen, it is easy to understand the other two estrogen regimens: estrogen plus progesterone combination regimen (why to add progesterone dydrogesterone 5mg or MPA 2-4mg? EMS is an estrogen-dependent disease, the combination regimen is more conducive to endometrial atrophy, but there are also reports on single estrogen regimen); Use tibolone continuously with a recommended dose of 1.25~2.5 mg/d (tibolone component: 7-methylenethinolone, its metabolites have three kinds of activities: estrogen, progesterone and androgen effects respectively, as a result, the compound effect is equivalent to the combination regimen.). Some Gynecologists often feel confused regarding the single progesterone regimen (norethindrone acetate 1.25-2.5mg, qd) together with its mechanism. This work is licensed under Creative Commons Attribution 4.0 License WJGWH.MS.ID.000521.