Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: A pilot study

Abstract

Introduction Adenomyosis is a benign uterine disease where endometrial glands and stroma are found within the myometrium surrounded by an area of hypertrophic myometrium. Symptomatology includes heavy menstrual bleeding and pelvic pain. The pathogenesis of adenomyosis is not known; however, animal models have shown increased uterine concentration of prolactin as a risk factor. Prolactin acts as a smooth muscle cell mitogen. If prolactin is central to adenomyosis pathogenesis, reducing uterine prolactin could be a possible medical treatment option. In this pilot study, we aim to evaluate the effect of bromocriptine, a prolactin inhibitor, on menstrual bleeding and pain in women with adenomyosis. Material and methods 23 women with diffuse adenomyosis were enrolled from a university hospital in Sweden and a tertiary care center in the USA. Nineteen patients completed 6 months of treatment with vaginal bromocriptine at a dose of 5 mg daily. Participants completed validated measures at baseline, 3 and 6 months of treatment, and at 9 months (3 months after cessation of bromocriptine). Validated measures utilized included Pictorial Blood Loss Assessment Chart (PBLAC), Aberdeen Menorrhagia Clinical Outcomes Questionnaire (AMCOQ), Visual Analog Scale for pain (VAS), McGill Pain Questionnaire (MPQ), Endometriosis Health Profile (EHP‐30), Female Sexual Function Index (FSFI) and the Fibroid Symptom Quality of Life (UFS‐QOL) symptom severity and health‐related quality of life (HRQL) subscores. Scores were compared between baseline and 9 months using the Wilcoxon signed rank test. Results Mean age of participants was 44.8 years. About 77.8% reported PBLAC scores >250 and 68.4% reported moderate to severe pain at baseline. Compared with baseline, women had lower 9‐month scores (median [interquartile range] for all) on PBLAC (baseline 349 [292‐645] vs 9‐month 233 [149‐515], P = 0.003), VAS (5.0 [4‐8.3] vs 2.5 [0‐4.5], P < 0.001), EHP Core Pain (15.9 [9.1‐50.0] vs 3.4 [2.3‐34.1], P = 0.029), EHP Core Self‐image (41.7 [16.7‐58.3] vs 25 [0‐5], P = 0.048) and Symptom Severity Score (60 [44‐72] vs 44 [25‐56], P < 0.001) and higher HRQL scores (57 [37‐63] vs 72 [51‐85], P < 0.001) following bromocriptine treatment. Other EHP core parameters and FSFI were not significantly different. Conclusions Significant improvement in menstrual bleeding, pain and quality of life after vaginal bromocriptine treatment suggests a novel therapeutic agent for adenomyosis.

Adenomyosis: Mechanisms and Pathogenesis

“…108 In humans, higher levels of PRL have been reported in women with than without adenomyosis, 109 and vaginal administration of bromocriptine significantly decreased menstrual bleeding and pain and improved quality of life in women with disease. 110 Mechanisms underlying elevated PRL and PRLR in the pathogenesis of adenomyosis are still unclear. In the normal bovine uterus, endometrial cells are the main source of PRL, whereas in the setting of adenomyosis, it is intensely synthesized by myometrial cells.…”

Serum prolactin and CA 125 levels in uterine adenomyosis

“…In humans, although vaginal bromocriptine therapy was found to improve adenomyosis symptoms, this study was performed by validated questionnaires without any clinical data. 9 Interestingly, in Yang et al's 10 study, no correlation was found between the PRL levels and uterine volume, but PRL levels declined significantly following ablation therapy in most of the patients. In the present study, no statistically significant difference was found between the percentage of patients with elevated PRL levels with the uterine size ⩽240 cm 3 and >240 cm 3 (p = 0.352).…”

“…[6][7][8] In humans, vaginal bromocriptine therapy has been found to reduce menstrual bleeding and pain in adenomyosis. 9 Furthermore, cancer antigen 125 (CA 125) and prolactin (PRL) levels were declined by ultrasound-guided percutaneous microwave ablation therapy in patients with adenomyosis. 10 CA 125 is best known as a marker of ovarian cancer; nevertheless, CA 125 levels were also elevated in adenomyosis, particularly with the enlarged uterine size of >12 gestational weeks or volume beyond 240 cm 3 in a previous study by Sheth and Ray.…”

Current and Future Medical Therapies for Adenomyosis

“…The effect of vaginal bromocriptine 46,47 was evaluated in women diagnosed with adenomyosis by either magnetic resonance imaging (MRI) or TVU findings in a single-arm study. 48 Bromocriptine was started at 1.25 mg daily and gradually escalated to a target dose of 5 mg daily. Treatment was continued for 6 months and outcomes evaluated at 3 and 6 months after 5 mg dosing and once more after cessation of bromocriptine for 3 months.…”