How useful is GnRHa in myoma?? :-Furthermore, gonadotropin-releasing hormone analogs
(GnRHa) has 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
UPA
is a 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.
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