Medical Therapy for fibroid management

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Patients who wish to avoid surgical treatment of symptomatic fibroids especially those close to menopause, the use of long -term medical therapy may be an alternative to avoid hysterectomy. This medical treatments approach can be achieved by combining GnRH agonist with low-dose sex- steroid hormone therapy, the so called add-back regimen. The GnRH agonists are produced by peptide substitutions at positions 6 and 10 which make them more potent (about 40-200), increase their resistance to proteolytic degradation. The agonist binds to the pituary receptors with high affinity and causes an initial stimulation if gonadotrophins production (the flare) followed by down regulation. There is therefore an initial stimulation of ovarian sex steroid production,which last several hours to few days followed by suppression this creating a hypoestrogenic/hypoprogestrogenic state, which causes uterine and fibroid reduction. Adding back a small amount of hormonal therapy allows minimization of side effects, while hopefully not impacting upon treatment efficacy.
Recently, specific GnRH binding sites-both high and low affinity-have been agonist and antagonist;this may suggest an additional direct effect of GnRH analogues on fibroid tissue.

Several pilot studies have investigated this approach, each utilizing only a handful of patients. Their data demonstrate that fibroid volume can be decreased satisfactorily with GnRH-agonist therapy and regrowth will not occur with the addition of low-dose sex steroid replacement (conjugated equine estrogens 0.yet mg/day and medroxuprogesterone acetate 10 mg 10 days/month). However, higher -dose medroxuprogesterone alone will apparently cause regrowth. Unfortunately follow up is limited to 1 year; long term results with approach of low -dose hormone replacement are unknown at this time.

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There is no consensus regarding the timing of administration of GnRH analogues in relation to the follicular phase there is unopposed oestrogen secretion due to the initial flare effects of the analogues, and an oestrogen withdrawal bleed occurs 10-14 days later.This may be a disadvantage especially if menorrhagia was the reason for the treatment of the fibroid. This time of commencement, however files out the possibility of administration during pregnancy. When begun in the luteal phase of the menstrual cycle , the elevation of the gonadotrophins and sex steroids is restricted to this phase and normal menstruation occurs without a subsequent withdrawal bleed in the following cycle.

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