Another treatment option is the use of a levonorgestrel intrauterine device (LNG-IUD), gestagens or combined oral contraceptives. In the subgroup of patients with ongoing family planning the medical treatment can only be an option as a pretreatment before reproductive procedures or as a prophylactic treatment in very young women with adenomyosis and a pregnancy wish in the future. In these cases a long-term treatment with low complication rates and the aim to prevent a worsening of the uterine situation is required. All medical therapeutic possibilities in patients with adenomyosis have been recently reviewed by various authors [20
]. The suppressive hormonal treatments with high dose progestins, oral contraceptives, LNG-IUDs, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors, selective estrogen receptor modulator (SERM) and selective progesterone receptor modulator (SPRM) are able to reduce symptoms by reduction of adenomyosis; however, each of these treatments is related to specific side effects. Currently, all medical approaches represent an off-label use as no medical solution is licensed in the specific treatment of adenomyosis. Dienogest is able to reduce adenomyosis-related pelvic pain and dysmenorrhea but is combined with a high risk of irregular uterine bleeding as the most common adverse reaction. Therefore, patients treated with dienogest have a certain risk of treatment discontinuation especially when they are of young age, have anemia before treatment and/or have mildly supressed or unsuppressed estradiol after starting dienogest treatment [22
]. Also, progestins such as norethisterone acetate or medroxyprogesteron acetate can reduce pain in patients with adenomyosis but are related to side effects, such as acne, edema and reduction of libido causing high discontinuation rates. Combined oral contraceptives represent another evidence-based therapeutic option. The data show a pain reduction but also bleeding disorders as the main adverse effect. The LNG-IUD seems to be the most effective option in reducing pain and menstrual blood loss [23
]. The LNG-IUDs can be used in women with completed family planning instead of hysterectomy, and as a maintenance therapy after adenomyosis surgery. In a retrospective analysis of treatment with LNG-IUD in patients with a large uterine adenomyosis and heavy menstrual bleeding, 10% underwent premature LNG-IUD removal and 16.7% underwent subsequent hysterectomy [24
]. The incidence of spontaneous expulsion of the IUD is higher in patients with adenomyosis and/or uterine fibroids than in women with a normal uterus and seems to depend on the insertion technique and the placement timing. The role of LNG-releasing intrauterine systems in the treatment of adolescent or very young women with adenomyosis, especially the use of low-dose IUDs should be investigated. The use of LNG-IUDs prior to assisted reproduction also has been described but has not yet been scientifically evaluated. Another medical treatment option is the use of GnRH agonists or antagonists. The application can be presurgical, postsurgical, prior to assisted reproductive techniques or as an individual approach instead of other medical treatments. The presurgical treatment can reduce complications and bleeding in adenomyosis surgery. The combination of GnRH agonist application with conservative surgery seems to result in longer symptom control and better reproductive outcomes in symptomatic and subfertile patients with adenomyosis compared with GnRH treatment alone. In infertile women with adenomyosis the treatment with GnRH agonists is indicated before fertility treatment in order to increase pregnancy and birth rates and decrease abortion rates [25
]. The efficacy of GnRH agonists in adolescents with refractory chronic pelvic pain, failed therapy with combined oral contraceptives and positive MR imaging for adenomyosis has been reported. The treatment improved symptoms and repeated MR imaging showed regression of the lesions [26
]. As estrogen, estrogen receptors and aromatase play a role in the pathogenesis of adenomyosis, the therapeutic use of aromatase inhibitors is an additional option. The reduction of adenomyosis volume and symptoms has been shown; however only a few publications exist and further investigations are needed. Selective progesterone receptor modulators, selective estrogen receptor modulators, valproic acid and antiplatelet treatment represent another group of treatment options, which needs to be investigated before used in the daily routine. So far, the medical treatment of adenomyosis especially in patients with ongoing family planning is an individual recommendation, while the situation in patients with completed family planning is based on a large number of publications, especially regarding the use of LNG-IUDs.