Re: GYN: GnRH analogues L
From: Peter Wein (p.wein@obsgyn-mercy.unimelb.EDU.AU)
Thu Feb 26 17:31:50 1998
>I'm interested in what you say about GNRH analogues. I have been very
>disapppointed, though I occasionally have the impression that the
>transverse diameter is reduced sometimes but rarely the length of the
>uterus.
>
>It so happens that my (UK-NHS) waiting time for hyst has been about 3
>months (now upto six) and it seemed simple to give 3 cycles of ZOladex
>whilst waiting.
>
>Anyone got any other positive or negative views on analogues?
>Malcolm Griffiths MD,MRCOG,MFFP,Cert.Mgmnt
>Obstetrician & Gynaecologist Luton & Dunstable Hosp.,UK.
>Tel: 01582-497459 (office) Fax: 01582-497376
> 01525-222849 (home) email: Malcolm@mgriff22.demon.co.uk
>http://www.obgyn.net/board/griffith.htm
>"CLINICAL FREEDOM IS THE LAST REFUGE OF THE CLINICALLY INCOMPETENT!"
>(Someone [1997])
>
>
There is some data to suggest that GnRH analogues may be of use for this - see references. When a registrar in Peterborough in 1991 (regards to Mr. Hackman) I was collecting data for ICI sponsored trial of goserelin for this purpose - never have seen the results published - has anyone? We did find that some patients got severe pain after GnRH form red degeneration of their fibroids - ( or something similar) - see a also reference 5 about bleeding.
Record 1 of 12 - MEDLINE EXPRESS (R) 1991
TI: A randomized trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas.
AU: Stovall-TG; Ling-FW; Henry-LC; Woodruff-MR
SO: Am-J-Obstet-Gynecol. 1991 Jun; 164(6 Pt 1): 1420-3; discussion 1423-5
AB: Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas, which were the size of 14 to 18 weeks' gestation, were randomized into two groups to determine whether preoperative gonadotropin-releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy. The control group (group A; n = 25) did not receive preoperative gonadotropin-releasing hormone agonist, but patients in Group B (n = 25) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy. Patients in the two groups were similar with respect to age, gravidity, parity, pretreatment uterine size, and hemoglobin and hematocrit levels. Patients in group B had an increase in hemoglobin levels (10.75 to 12.12 gm/dl, p less than 0.05) and a decrease in uterine volume (1086.7 to 723.4 ml, p less than 0.05) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy (76.0% vs 16%). Patients in group B also had shorter hospitalizations (5.2 vs 3.8 days, p less than 0.05). We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas.
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----------------------------------------------------------------------------Record 2 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: GnRH agonists before surgery for uterine leiomyomas. A review.
AU: Crosignani-PG; Vercellini-P; Meschia-M; Oldani-S; Bramante-T
SO: J-Reprod-Med. 1996 Jun; 41(6): 415-21
AB: OBJECTIVE: To clarify whether preoperative treatment with gonadotropin-releasing hormone (GnRH) agonists offers substantial advantages to patients undergoing conservative or definitive surgery for uterine leiomyomas. STUDY DESIGN: A review of data from the most recent English-language literature. RESULTS: Inducing amenorrhea in patients with heavy menorrhagia and severe sideropenic anemia before both conservative and definitive surgery for uterine fibroids raises hemoglobin and hematocrit values to within the normal range, limits homologous blood transfusions and enables operations to be scheduled with the patients in better condition. A temporary 30-50% reduction in mean uterine volume theoretically may convert an abdominal into a vaginal hysterectomy in "borderline" cases or sometimes allow a transverse instead of longitudinal abdominal incision. No trial has yet demonstrated "clinically" significant reductions in operating time, operative blood loss or postoperative morbidity in patients undergoing myomectomy or hysterectomy after a course of GnRH agonists as compared with those operated on immediately. There seems insufficient scientific evidence to justify the routine use of GnRH agonists before myomectomy at laparotomy, except possibly in the case of extremely bulky uteri. GnRH agonist treatment before hysteroscopic myomectomy induces endometrial thinning, reduces bleeding and mucous debris, and decreases the diameter of submucous leiomyomas, improving visibility and limiting operating time and fluid intravasation. CONCLUSION: The available data seem to support the use of GnRH agonist treatment before surgery for uterine leiomyomas in selected circumstances. Administration of GnRH agonist for only two or three months preoperatively seems to achieve all the advantages of this treatment, limiting side effects and cost.
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----------------------------------------------------------------------------Record 3 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Decrease in symptoms, blood loss and uterine size with nafarelin acetate before abdominal hysterectomy: a placebo-controlled, double-blind study.
AU: Ylikorkala-O; Tiitinen-A; Hulkko-S; Kivinen-S; Nummi-S
SO: Hum-Reprod. 1995 Jun; 10(6): 1470-4
AB: To evaluate the efficacy and safety of nafarelin before hysterectomy in a prospective placebo-controlled trial, we randomized 188 pre-menopausal women with uterine fibroids (n = 111), menometrorrhagia (n = 58) or pelvic pain (n = 19) to receive either nafarelin (200 micrograms twice daily as a nasal spray) or a placebo for 3 months before abdominal hysterectomy. The data analysis could be performed in 166 women, of whom 107 received nafarelin and 59 a placebo. Nafarelin led to a rise in blood haemoglobin (5.5 g/l) and to a decrease in uterine volume (23.7%). This, however, gave no objective benefit during surgery (similar operative durations and blood losses). The uteri from patients treated with nafarelin (255.5 +/- 12.6 g, mean +/- SD) were significantly lighter (P = 0.029) than those from patients treated with a placebo (346.2 +/- 35.7 g). Histological examination of the fibroids or uteri revealed changes typical for hypo-oestrogenism, but no specific histological pattern could be established. The endometrium was proliferative in 56% and showed mild hyperplastic features in 10% of patients given nafarelin, whereas the respective figures for the placebo group were 41 and 0%. Hot flushes were the most common side-effects, being reported by 61% in the nafarelin group and 35% in the placebo group. Nafarelin can be useful as a pre-surgical adjunct in a patient scheduled for abdominal hysterectomy if there is a need to raise the haemoglobin concentration or to reduce the size of the uterus.
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----------------------------------------------------------------------------Record 4 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Trial of routine gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma.
AU: Balasch-J; Manau-D; Mimo-J; Duran-M; Puerto-B; Vanrell-JA
SO: Acta-Obstet-Gynecol-Scand. 1995 Aug; 74(7): 562-5
AB: OBJECTIVE. To investigate the usefulness of a routine short term treatment with gonadotropin releasing hormone agonist (D-Trp-6-LHRH depot) before abdominal hysterectomy for leiomyoma. STUDY DESIGN. Prospective, comparative, randomized study. SETTING. A teaching hospital of Barcelona University. PATIENTS. Fifty premenopausal women requiring hysterectomy as treatment for symptomatic leiomyomas. Twenty-three patients were randomized to receive gonadotropin releasing hormone agonist treatment before hysterectomy (cases), and 27 patients were randomized to immediate hysterectomy (controls). MAIN OUTCOME MEASURES. Type of abdominal incision, operating time, operative hemoglobin and hematocrit decrease, postoperative morbidity, and days in hospital. RESULTS. In the agonist treated group mean uterine volume decreased and mean hemoglobin and hematocrit significantly rose after 8 weeks of treatment. Operative time was similar in both groups of patients but the number of women having Pfannenstiel incision was significantly higher in the cases. Mean operative hemoglobin and hematocrit decrease and postoperative morbidity were lower in the cases. There was a trend for shorter postoperative hospital stays in the agonist treated group. CONCLUSIONS. Our results favor the routine use of a short term gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma in order to decrease operative blood loss and postoperative morbidity.
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----------------------------------------------------------------------------Record 5 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Early severe haemorrhage complicating GnRH analogue treatment of submucous uterine fibroids.
AU: Gregora-M; Forbes-K; Hill-B
SO: Aust-N-Z-J-Obstet-Gynaecol. 1995 Feb; 35(1): 111-2
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----------------------------------------------------------------------------Record 6 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Goserelin reduction of uterine fibroids prior to vaginal hysterectomy.
AU: Eizenberg-DH
SO: Aust-N-Z-J-Obstet-Gynaecol. 1995 Feb; 35(1): 109-10
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----------------------------------------------------------------------------Record 7 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Use of GnRH agonist before hysterectomy: a cost simulation.
AU: Bradham-DD; Stovall-TG; Thompson-CD
SO: Obstet-Gynecol. 1995 Mar; 85(3): 401-6
AB: OBJECTIVE: To evaluate the potential savings in cost of care derived from performing vaginal hysterectomies instead of abdominal hysterectomies in selected women with fibroid uteri equivalent in size to a 14-18 week gestation. METHODS: Women 35-46 years of age undergoing hysterectomy for fibroid uteri were selected to allow application of conversion rates gained in a separate randomized study using leuprolide acetate depot 3.75 mg. Statewide public data for North Carolina's hospital discharges provided relative rates of hospital charges and leiomyomas for all hysterectomies, by age. Professional charges were omitted from the analysis. Estimated savings were projected to the national level. RESULTS: During 1992 in North Carolina, 18,110 inpatient hysterectomies were performed for women of all ages; 28.1% of these were for uterine leiomyomas. For women 35-46 years old (12.7% of all hysterectomies), there were 1904 abdominal and 390 vaginal hysterectomies; the mean total charge for abdominal hysterectomy was $5590, and $4732 for the vaginal alternative. These statewide data provide missing elements to allow a national estimate of the potential savings of using GnRH agonist preoperatively. The projected national savings, if 1987 utilization data are used, was $4.6 million, nearly 1.4% of the inpatient charges. The 1992 value of these savings is $6.7 million. CONCLUSION: The use of preoperative GnRH agonist therapy before hysterectomy for patients with a uterine size equivalent to a 14-18 week gestation represents a significant cost-saving alternative, increasing the use of vaginal hysterectomy and resulting in potential savings in direct inpatient medical care charges.
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----------------------------------------------------------------------------Record 8 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids.
AU: Lumsden-MA; West-CP; Thomas-E; Coutts-J; Hillier-H; Thomas-N; Baird-DT
SO: Br-J-Obstet-Gynaecol. 1994 May; 101(5): 438-42
AB: OBJECTIVE: To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss. DESIGN: Randomised placebo-controlled study. SETTING: Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle. SUBJECTS: Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy. INTERVENTIONS: After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment. MAIN OUTCOME MEASURES: Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications. RESULTS: Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P << 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision. CONCLUSIONS: This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata.
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----------------------------------------------------------------------------Record 9 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Gonadotropin-releasing hormone agonist use before hysterectomy [see comments]
AU: Stovall-TG; Summit-RL Jr; Washburn-SA; Ling-FW
SO: Am-J-Obstet-Gynecol. 1994 Jun; 170(6): 1744-8; discussion 1748-51
AB: OBJECTIVE: Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy. STUDY DESIGN: Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist. RESULTS: All patients in the two groups with a pretreatment hemoglobin << 11.0 gm/dl randomized to agonist had a significant (p << 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p << 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms. CONCLUSION: The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin << 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity.
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----------------------------------------------------------------------------Record 10 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Gonadotropin-releasing hormone agonists: utilization before hysterectomy.
AU: Stovall-TG
SO: Clin-Obstet-Gynecol. 1993 Sep; 36(3): 642-9
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----------------------------------------------------------------------------Record 11 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Gonadotropin releasing hormone agonist treatment before hysterectomy for menorrhagia and uterine leiomyomas.
AU: Vercellini-P; Bocciolone-L; Colombo-A; Vendola-N; Meschia-M; Bolis-G
SO: Acta-Obstet-Gynecol-Scand. 1993 Jul; 72(5): 369-73
AB: OBJECTIVE. To investigate the effect of gonadotropin releasing hormone agonist (goserelin) treatment before hysterectomy for leiomyomata-associated menorrhagia. DESIGN. Prospective, comparative, nonrandomized study. SETTING. A teaching hospital of Milano University. PATIENTS. Anemic women requiring hysterectomy for myoma-associated menorrhagia. INTERVENTION. Six months' preoperative goserelin treatment (41 cases) or immediate surgery (92 controls). MAIN OUTCOME MEASURES. Abdominal/vaginal hysterectomy rate, number of transfusions, operating time, blood loss, complications, febrile morbidity, and days in hospital. RESULTS. In the goserelin group mean hemoglobin rose (8.5 versus 13.3 g/dl) and mean uterine volume decreased (528 versus 251 ml). At preoperative pelvic exploration abdominal hysterectomy was indicated in 22 (54%) cases and 74 (80%) controls and vaginal hysterectomy in 19 (46%) and 18 (20%) (relative risk 3.6, 95% confidence interval 1.6 to 7.7; p = 0.001). No case required a transfusion whereas 51% of controls needed a total of 127 packed red cell units. CONCLUSIONS. In anemic women with menorrhagia and leiomyomas, gonadotropin releasing hormone agonist treatment before hysterectomy limited transfusion requirements and increased the vaginal procedure rate.
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----------------------------------------------------------------------------Record 12 of 12 - MEDLINE EXPRESS (R) 1992-1996
TI: Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata.
AU: Golan-A; Bukovsky-I; Pansky-M; Schneider-D; Weinraub-Z; Caspi-E
SO: Hum-Reprod. 1993 Mar; 8(3): 450-2
AB: To determine whether pre-operative treatment with gonadotrophin-releasing hormone (GnRH) analogue may have a beneficial effect on surgery outcome, 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy (TAH), were randomly divided into a study group (n = 29) and a control group (n = 24). The study group of patients were treated by an i.m. injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery. The control group had no pre-operative treatment. Haemoglobin concentration and oestradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery, and at surgery. The duration of surgery was shorter in the study group (49 versus 70 min in the hysterectomy group) and intra-operative blood loss was less (208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies). Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery, and diminishing the intra-operative blood loss in surgery for fibroid uteri. Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri.
<bigger>Peter Wein
</bigger>Senior Lecturer
Department of Obstetrics and Gynaecology
University of Melbourne, Mercy Hospital for Women
Clarendon Street, East Melbourne 3002
Australia
Tel: +61 3 9270 2556 Fax: +61 3 9417 5406 Mobile: 0414 691690
