Selective progesterone receptor modulators for fertility preservation in women with symptomatic uterine fibroids†

Abstract

Uterine fibroids (UFs, AKA leiomyoma) are the most important benign neoplastic threat to women's health, with costs up to hundreds of billions of health care dollars worldwide. Uterine fibroids caused morbidities exert a tremendous health toll, impacting the quality of life of women of all ethnicities, especially women of color. Clinical presentations include heavy vaginal bleeding, pelvic pain, bulk symptoms, subfertility, and obstetric complications. Current management strategies heavily lean toward surgical procedures; nonetheless, the choice of treatment is generally subject to patient's age and her desire to preserve future fertility. Women with UF who desire to maintain future fertility potential face a dilemma because of the limited treatment choices that are currently available to help them achieve that goal. Recently, ulipristal acetate the first of the promising family of oral selective progesterone receptor modulators has been approved for UF treatment in Europe, Canada, and several other countries and is under review for possible approval in the USA. In this review article, we discuss recent advances in the management options against UF with a bend toward oral effective long-term treatment alternatives who are particularly suited for those seeking to preserve their future fertility potential. We also explore the transformative concept of primary and secondary UF prevention using these new anti-UF agents. We envision a remarkable shift in the management of UF in future years from surgical/invasive treatment to orally administrated options; clearly, this potential shift will require additional intense clinical research.

Uterine fibroid therapy: the pharmacokinetic considerations

“…UF growth is hormonal dependent on estrogen and most importantly progesterone. Therefore, current treatments aim to suppress or modulate these ovarian sex hormones [1]. Herein we will focus on the most commonly used treatment options, other possible treatment options include aromatase inhibitors, oral contraceptives, Levonorgestrel-releasing intrauterine system, Selective estrogen receptor modulators, localized treatments (gene therapy and collagenase), and alternative medicine (green tea and Vitamin D) can be found in more details in literature [1,3].…”

“…Considering the high expression level of progesterone receptors in UF compared to adjacent myometrium, SPRMs family offered a promising globally recognized treatment option with a tissue selective mixed progesterone agonist/antagonist effect [1]. In the past recent years, much interest has emerged around this family members and have been investigated for UF treatment including the forefront Ulipristal acetate (UPA), Vilaprisan, Asoprisnil, and Telapristone (Proellex).…”

“…Ultrasound based epidemiological studies disclosed that 70 −80% of these women will develop UFs by age of 50. Although inherently benign, this enigmatic disease constitutes a major health and financial burden worldwide, also, it presents a major health disparity challenge for being at least four times more common in women of color [1].…”

“…UFs associated symptoms negatively impact daily living as well as overall quality of life of approximately 20-30% of afflicted patients. This includes abnormal uterine bleeding with subsequent anemia, bulk symptoms, obstetrical complications and recently possible infertility [1,2].…”

“…Historically, Hysterectomy has been the most common treatment option for symptomatic UFs. Yet, many factors halt that preference including, its invasive nature as well as uterus and consequently fertility deprivation [1,2]. In regard to alternatives like pharmacological treatment, unfortunately, majority of the current therapies offer inadequate or short-term control of symptoms and cannot be used for long term because of safety concerns [3].…”