ULIPRISTAL & Myoma

How useful is GnRHa in myoma?? :-Furthermore, gonadotropin-releasing hormone analogs (GnRHa) proved to be successful both as a conservative treatment and as a preoperative therapy of myomas. They are highly effective in reducing both the symptoms (bleeding, anemia, and abdominal pain) and the volume of fibroids. However, these effects are transient and the myomas usually return to pre-therapy size within a few months of discontinuation. Preoperative GnRHa treatment before myomectomy decreases the size and vascularity of the myoma but may make the capsule more fibrous and hence difficult to resect. Furthermore, some of the treatment-associated adverse effects (menopausal symptoms, osteoporosis, and pelvic pain) could benefit from a hormonal add-back although it may reduce the beneficial effects of GnRHa on myoma size.

How useful is Letrozole in myoma?? Aromatase inhibitors appear as effective as GnRHa, Recently, the potential therapeutic role of non-steroidal aromatase inhibitors has been suggested. Aromatase inhibitors appear as effective as GnRHa, and have fewer side effects. However, the use of these drugs is presently restricted to infertile women due to the unknown influence of body mass index on treatment efficacy, the sparse data on subsequent reproductive outcome, and the absence of long-term follow-up data.

Ulipristal & myoma ?? Mechanism of action of Ulipristal acetate in the treatment of uterine fibroids

Selective progesterone-receptor modulators (SPRMs) are a new class of PR ligands displaying tissue-selective agonist/antagonist/mixed activity on target cells. UPA is an orally active synthetic SPRM, characterized by a tissue-specific partial progesterone antagonist effect. Progesterone normally promotes fibroid growth in two ways: on the one hand, it up regulates epidermal growth factor (EGF) and Bcl-2 gene, on the other hand it down regulates the tumor necrosis factor gene (TNF).

 UPA, as a progesterone antagonist, inhibits the proliferation of leiomyoma cells and induces apoptosis by increasing cleaved caspase-3 expression and decreasing Bcl-2 expression.

Moreover, UPA down regulates the expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and their receptors. Thus, it suppresses neo-vascularization, cell proliferation, and survival in leiomyoma cells but not in normal myometrial cells. Additionally, UPA increases the expression of matrix metalloproteinases (MMPs) and decreases the expression of tissue inhibitor of metalloproteinases (TIMPs) and collagens in cultured fibroid cells. Thus, UPA may impair fibroid tissue integrity by reducing the deposition of collagen in the extracellular spaces.

Besides, UPA acts on the hypothalamic–pituitary–ovarian axis, thereby inhibiting or delaying ovulation and inducing amenorrhea. Since UPA does not alter basal levels of luteinizing hormone and follicle stimulating hormone, estradiol levels remain within the physiological mid-follicular range (60–150 pg/mL) and hence the symptoms of estrogen deprivation do not occur. However, UPA induces amenorrhea in most women due to its interaction with endometrial progesterone receptors.In conclusion, UPA selectively acts on uterine fibroids and their related symptoms and represents a promising new option for the pre-surgical medical treatment of uterine fibroids. In uterine fibroids estrogen and progesterone receptors are expressed at higher levels than in normal myometrium. The influence of estrogen on fibroid growth is well-known, while the role of progesterone and the progesterone-receptor (PR), as well as ovarian steroids has emerged only recently. In fact, biochemical and clinical studies have suggested that the Ostrogen may enhance proliferative activity in fibroids and the progesterone  may influence fibroid growth. These observations have inspired studies testing the efficacy of anti-progestins in the medical management of uterine fibroids.