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B8. Use of Antiprogestins in the Management of Endometriosis and Leiomyoma
Pages 189-209

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From page 189...
... Infertility, pelvic pain, and uterine bleeding are major clinical manifestations. Although their pathogeneses are unclear, both conditions are ovarian steroid dependent, and tumors are endowed with receptors for estrogen (ER)
From page 190...
... Future studies of lower doses and correlation of individual responses with the status of steroid hormone receptors, growth factors, anatomical sites, and vascularly may be helpful in predicting maximal responses of individual patients. INTRODUCTION Pelvic endometriosis and uterine leiomyomas (fibroids)
From page 191...
... The beneficial effect of a GnRH agonist on endometriosis is similar to that of Danazol, but it is devoid of androgenic and anabolic effects. However, the profound hypoestrogenic state and the associated consequence of severe hot flushes and a reduction of bone mass are major limitations for its long-term use (Matte et al., 1988a; Rummon et al., 1988~.
From page 192...
... After an initial transient rise in E~G levels during the first month of treatment, values comparable to the early to midfollicular phase range of normal-cycling women (Figure B8.1) were maintained.
From page 193...
... daily urinary ERG and PdG levels in 13 normally cycling women. Data are centered around the day after the ERG peak (day 0)
From page 194...
... These preliminary findings offered promise for future investigations using lower doses and longer-term therapy with RU 486, with the aim of avoiding the antiglucocorticoid effect and allowing sufficient time for the
From page 195...
... H T Baseline RU486 30 20 3, In <, o 10 t o FIGURE B8.3 Clinical scores for pelvic pain and AFS scores for endometriotic implants before and after six months of RU 486 treatment at 50-mg daily dose (*
From page 196...
... A follow-up study, using a 5-mg daily dose for six months, was conducted in patients with symptomatic endometriosis. In this ongoing study, four patients have completed treatment (three are ongoing)
From page 197...
... therapy using antiprogestins in symptomatic endometriosis when fertility is not an issue. In summary, RU 486 at a 50-mg dose, and possibly at a 5-mg dose for a period of six months has resulted in impressive therapeutic effectiveness.
From page 198...
... That progesterone may play a role in leiomyoma growth is suggested by the finding of a higher mitotic count in leiomyomas obtained during the secretory phase than in the proliferative phase of the menstrual cycle (Kawaguchi et al., 1988~. Additionally, when the GnRH agonist and a progestin are coadministered, the expected regression of leiomyoma size observed with the GnRH agonist alone is not achieved (Friedman et al., 1988~.
From page 199...
... Uterine arterial flow was analyzed by a duplex sonography combining real-time imaging and pulsed Doppler velocimetry by transvaginal scanning. Doppler waveforms were computed and expressed as vascular resistance index (RI)
From page 200...
... for six months (Friedman et al., 1991~. Although all but one patient displayed a decrease in leiomyoma volume, individual variations ranging from 15 percent to 90 percent in response to RU 486 were apparent (Figure B8.6
From page 201...
... A transient elevation in serum transaminases accompanied by joint pain was seen at the end of treatment in one patient, with rapid resolution after discontinuation of RU 486. There was no significant change in bone mineral density of the spine and hips after three months of therapy (0.8 + 0.319 versus 0.835 + 0.713 gAcm2~.
From page 202...
... 25- and 5-mg Doses The effect of reduced doses of RU 486 on leiomyoma volume was evaluated in three-month treatment with a 25-mg daily dose in 17 patients, and 5 mg in 7 patients. All patients were monitored as described above, with the exception that 24-hour urinary free cortisol was used as an index of antiglucocorticoid effects instead of serum cortisol.
From page 203...
... As with the 50-mg daily dose, all patients became amenorrheic during their treatment. Five patients experienced atypical hot flushes during the first month of treatment, and two patients who used the 25-mg daily dose had mild elevations of liver transaminases, which resolved within one month after they discontinued the medication.
From page 204...
... 204 lo A' _ ~ ~ ~ ~ ~ ~ .
From page 205...
... recorded from the uterine arteries after three months of treatment as compared to pretreatment values recorded during the early follicular phase. This finding resembled that reported after GnRH agonist therapy for leiomyoma (Matte et al., 1988b)
From page 206...
... . volume unaccompanied by antiglucocorticoid effects.
From page 207...
... . Revised American Fertility Society classification of endometriosis.
From page 208...
... Kawaguchi, K., Fuji, S., Konishi, I., et al. Mitotic activity in uterine leiomyomas during the menstrual cycle.
From page 209...
... Reversible trabecular bone density loss following induced hypo-oestrogenism with the GnRH analogue buserelin in premenopausal women. Clinical Endocrinology 29:45-51, 1988a.


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