Treatment of uterine leiomyomas with luteinizing hormone-releasing hormone antagonist Cetrorelix

The efficacy of the luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) in the medical management of uterine leiomyomas (fibromas) was evaluated. Cetrorelix was administered to 18 pre- menopausal women with myomas with a mean age of 33.3 years, who had been candidates for hysterectomy. The initial dose of Cetrorelix was 5 mg twice daily s.c. for the first 2 days and thereafter 0.8 mg was given twice daily s.c. for at least 3 months. The mean duration of the treatment was 4.4 months. Before the therapy with Cetrorelix, the mean uterine volume, measured by ultrasonography, was 395.4 +/- 69.2 ml (range 89-1166). Sixteen patients showed a progressive reduction in uterine volume from 410.4 +/- 77.1 to a mean of 230.8 +/- 52.6 ml at 3 months. All patients became amenorrhoeic and had hot flushes. After treatment with Cetrorelix, a surgical myomectomy was performed in 12 women. One of the patients subjected to myomectomy after therapy with Cetrorelix became pregnant. These patients have been followed for up to 25 months and only in one case has the uterine volume increased after therapy. Three patients had good responses to therapy with Cetrorelix and it was decided to follow them only by observation. One patient became pregnant 2 months later. In the other patient, the uterine volume remained unchanged for the duration of the follow-up of 2 years and the third patient showed an increase after 21 months. In three patients, it was necessary to perform total hysterectomy. In 14 patients, serum concentrations of luteinizing hormone, follicle stimulating hormone and oestradiol decreased after the administration of the first dose of Cetrorelix and continued at subnormal values throughout therapy. In 15 patients who were not subjected to total hysterectomy, menstrual function returned at 1 month after cessation of treatment. Overall results support the use of Cetrorelix for the management of uterine leiomyomas.      

Endocrinology: Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen--progestin or progestin 'add-back' for 2 years

Treatment of women with leiomyomata with gonadotrophin releasinghormone agonists (GnRHa) for >6 months is not recommendedbecause of concerns regarding adverse sequelae of prolongedhypoestrogenism. It has been postulated that addition of low-dosesex steroids to GnRHa treatment, i.e. ‘add-back’therapy, may avert some of these adverse effects (acceleratedbone resorption, vasomotor flushes) without altering the efficacyof GnRHa therapy. To evaluate the effects of long-term GnRHatherapy on uterine size, bleeding patterns, bone mass and lipids,51 pre-menopausal women with leiomyomata were treated with theGnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2years. After 3 months of leuprolide therapy, the women wererandomized to receive either low-dose continuous oestropipate,0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1—14each month (the oestrogen–progestin add-back group) orhigher-dose norethindrone, 10 mg daily (the progestin add-backgroup), for the remaining 21 months. Mean uterine volume decreasedby 40% in both treatment groups during the first 3 months onleuprolide treatment. There was no significant change in uterinesize following oestrogen–progestin add-back. However,mean uterine volume in the progestin add-back group increasedto 87% of pre-treatment size by treatment month 12 and 95% ofpre-treatment size by treatment month 24. Mean bone densityof the lumbar spine as measured by dual X-ray absorptiometrydecreased significantly by 2.6% during the first 3 months inall patients, but did not change significantly following steroidadd-back in both treatment groups during the final 21 treatmentmonths. There were parallel and significant increases in meanhaematocrits (Hct) of 4.8% in the oestrogen—progestingroup and 7.8% in the progestin group over the 2-year treatmentperiod. Mean serum high density lipoprotein (HDL) cholesterolconcentration was unchanged in the oestrogen—progestinadd-back group but decreased by 36% in women receiving progestinadd-back. By 6 months after completion of treatment, mean uterinevolume, leiomyoma-related symptoms, Hct and bleeding patternshad returned to pre-treatment values. Thus, the oestrogen—progestinadd-back regimen was superior or equal to the progestin add-backregimen in all safety and efficacy parameters studied; the latterregimen was associated with regrowth of myomatous uterine volumeand with marked depression of cardio-protective HDL cholesterolconcentrations. One 50 year old woman in the oestrogen—progestingroup developed a leiomyosarcoma which was suspected by sonographicchanges in leiomyoma appearance and was thought to be unrelatedto treatment. In conclusion, GnRHa plus oestrogen—progestinadd-back therapy may provide a long-term (i.e.>6 month) medicaltreatment option in women with leiomyomata.     

Long term effects of Tibolone on postmenopausal women with uterine myomas.

OBJECTIVES: The aim of the present study is to evaluate the long term effects of Tibolone (Livial) on uterine myomas volume as well as on uterine arteries pulsatility index (PI) in postmenopausal women. METHODS: This study included 66 naturally menopausal women. Twenty of them (group A) had no uterine myomas; 23 of them (group B) had a single, asymptomatic, intramural or subserous myoma of a maximum diameter less or equal than 2 cm; 23 of them (group C) had a single, asymptomatic, intramural or subserous myoma of a maximum diameter between 2 and 5 cm. The volume of the myomas as well as the pulsatility index of the uterine arteries was assessed by transvaginal ultrasonography every 6 months after administration of Tibolone (2.5 mg daily). RESULTS: No statistically significant difference on myomas volume was found after a 3-year period of Tibolone administration. The uterine artery basal PI was significantly higher in group A compared to that of groups B and C. After 6 months of Tibolone administration the PI in group A was significantly lower compared to the basal one whereas in groups B and C was significantly higher compared to the basal value. CONCLUSIONS: Our results suggest that treating postmenopausal woman with Tibolone on a long-term basis: (a) does not increase the volume of uterine myomas and (b) has an early effect on uterine haemodynamics (decrease of PI in women without myomas and increase of PI in women with myomas).     

Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT

OBJECTIVES: It is still controversial whether hormone replacement therapy (HRT) can affect the onset of uterine myomas or their growth in postmenopause. It is likely that some therapeutic schedules can influence the myometrial growth differently, due to a more potent stimulation of the uterine receptors. The aim of the present study is to evaluate the effects of two different hormonal treatment schedules on the risk of uterine myoma onset or progression. METHODS: In a 2 year prospective randomised study we compared an oral cyclic association of oestradiol valerate and cyproterone acetate versus a sequential combination of transdermal E(2) and per oral medrossiprogesterone acetate on 240 postmenopausal women with and without uterine myomas. RESULTS: Among the patients without uterine myomas treated with the transdermal-oral combination we noted the onset of myomas in 5% of cases after 24 months of treatment, while no new uterine formation was observed for the orally treated women (P<0.01). Among the patients with uterine myomas at the beginning of the study, in the group transdermally treated we found a mean increase in myoma volumes of 25.3% in the following 24 months, which was significantly different compared with the initial volume of myomas. On the other hand, women treated with the oral combination showed no significant modification of myoma volumes at the end of the study. CONCLUSIONS: Percutaneous-oral schedule of HRT seems to affect the growth of uterine myomas more than a single oral combination of oestradiol valerate and cyproterone acetate.     

Endocrinology: Sequential gonadotrophin-releasing hormone agonist/ low-dose oral contraceptive treatment for leiomyomata uteri

On the basis that gonadotrophin-releasing hormone agonists (GnRHa)induce a significant but transient shrinkage of leiomyomas andthat oral contraceptive use may be associated with a decreasedrisk of fibroids, we tested the hypothesis that sequential GnRHa/low-doseoral contraceptive treatment could be a therapeutic alternativein perimenopausal women with uterine fibroids. Six premenopausalwomen with leiomyomata uteri were treated with D-tryptophan-6-luteinizinghormone-releasing hormone (D-Trp-6-LHRH) depot (Decapeptyl 3.75)for 6 months and demonstrated a significant reduction in meanuterine volume. A low-dose oral contraceptive containing 30µg of ethinyl oestradiol plus 150 µg of desogestrelwas given during the ensuing 12 months. When GnRHa therapy wasdiscontinued, there was a rapid regrowth of the uterine fibroidsand the uterine volume had reached, or even exceeded, pretreatmentvalues by the eighth to 12th month of contraceptive therapy.Sequential GnRHa/low-dose oral contraceptive treatment is nota useful tool for leiomyomata uteri.     

Efficacy of preoperative medical treatment in facilitating hysteroscopic endometrial resection, myomectomy and metroplasty: literature review

The evidence of the efficacy of preoperative medical treatment with danazol, gonadotrophin releasing-hormone agonists (GnRHa) or progestins in facilitating surgery and improving the long-term results of myomectomy, hysteroscopic metroplasty and endometrial resection has been reviewed. Sixteen randomized and non-randomized controlled clinical trials, published in the English literature between 1990 and 1996, were identified. In all studies comparing GnRHa or danazol versus no treatment, fluid absorption during surgery was less in subjects who underwent medical treatment independently of the drug used and the type of intervention, the reduction ranging from 142 to 572 ml. A reduction in operating time (between 2 and 25 min) was observed in both the danazol and GnRHa-treated groups in comparison with untreated controls, regardless of the type of operation (endometrial resection, myomectomy or metroplasty). With regard to long-term results, amenorrhoea tended to be more frequent in patients who received GnRHa: the pooled odds ratio (OR) of amenorrhoea for GnRHa-treated women compared with untreated controls was 2.0 [95% confidence interval (CI), 1.1-3.8]. In studies comparing GnRHa with danazol, no marked differences were observed in mean operating time, but the OR of amenorrhoea at 6-12 months after surgery was 1.9 (95% CI 1.0-3.3).      

Medroxyprogesterone acetate with Zoladex for long-term treatment of fibroids: effects on bone density and patient acceptability

A randomized trial was carried out to investigate the effect of 12 months administration of the gonadotrophin-releasing hormone agonist (GnRHa) Zoladex in combination with either placebo or medroxyprogesterone acetate (MPA) from the third month. Bone density, markers of bone resorption, symptoms and uterine volume were monitored in 24 women with symptomatic fibroids or menstrual problems. A total of 21 women were recruited to act as controls for the assessment of bone parameters. Vasomotor side-effects were reduced significantly in the MPA-treated group. The reduction in uterine volume in women with fibroids was not impaired by the addition of MPA. The bone markers osteocalcin and alkaline phosphatase were assessed in plasma, and the cross-links pyridinoline and deoxypyridinoline measured in urine. Changes in these markers are reported which suggest increases in bone resorption during the period of observation. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at the spine and forearm. The net reduction in BMD at the spine in the treated groups was 4.30 +/- 0.59% at 6 months and 7.50 +/- 0.78% at 1 year, with no change in the control group. No change was seen in forearm BMD. No protective effect was observed when MPA was added. At 1 year after the completion of treatment, BMD remained significantly below baseline, and this has implications for the prolonged use of GnRHa.      

Pulsatile gonadotrophin secretion in women with polycystic ovary syndrome after gonadotrophin-releasing hormone agonist treatment

In polycystic ovary syndrome (PCOS), increased luteinizing hormone (LH) pulse frequency has been attributed to either the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator or ovarian oestrogen feedback. To address this issue, a detailed examination of pulsatile LH secretion was undertaken during recovery from GnRH agonist (GnRHa) suppression. Each of six women with PCOS and six normal ovulatory women received daily GnRHa treatment for 14 weeks. Frequent blood samples were collected and assayed for gonadotrophins, androgens and oestrogens before, during and up to 4 weeks after treatment. Women with PCOS had higher basal LH pulse frequency and amplitude and increased serum concentrations of LH, androstenedione, testosterone and oestrone than controls. After 3 months of GnRHa treatment, all these parameters were suppressed with no differences observed between the two groups. One week after cessation of GnRHa, LH pulse frequency promptly returned to pre-treatment range with no between-group differences noted, whereas LH pulse amplitude, serum gonadotrophins and ovarian steroids remained maximally suppressed and equivalent in the two groups. Subsequent LH pulse frequency remained constant while LH pulse amplitude and circulating concentrations gradually increased in parallel with a return of serum oestrogen to pre-treatment values. Despite comparable resumption of LH secretion in the two groups, corresponding androgen concentrations in women with PCOS were greater than those of normal ovulatory women. Thus, the immediate restoration of LH pulse frequency after discontinuing GnRHa treatment is largely independent of ovarian oestrogen production and reflects primacy of the GnRH pulse generator in determining basal LH pulse frequency. Equivalent LH pulse frequency rates in the two groups during the recovery period do not suggest an intrinsic hypothalamic-pituitary hyperactivity in PCOS.      

Effects of hormone replacement therapy on postmenopausal uterine myoma

OBJECTIVES: To evaluate the effects of sequential continuous hormone replacement therapy (HRT) on myoma size and on pulsatility index (PI) of uterine arteries and to verify the correlation between uterine artery flow impedance and the growth rate of myoma in women receiving HRT. METHODS: In a prospective 1-year study 60 postmenopausal women were enrolled into three study-groups to receive continuous transdermal 17beta-oestradiol 0.05 mg/day plus nomegestrolo acetate 5 mg/day sequentially added: 20 patients (group A) unaffected by uterine myomas, 20 patients (group B) with single asymptomatic myoma <3 cm/14 cm3, 20 patients (group C) with single asymptomatic myoma >3 cm/14 cm3. The changes in myoma volume and in PI were assessed by means of transvaginal ultrasonographic scan every 3 months. The patients with myoma were divided into two subgroups: quiescent myoma (B1, C1) and growing myoma (B2, C2). RESULTS: No significant increase of uterine fibroids volume was found after 1-year HRT (24.14+/-20.02-->28.81+/-30.02 cm3). Six out of eight myomas growing during HRT belonged to group C. The uterine artery basal PI value of group A was significantly higher (P<0.01) than the corresponding PI in group B and C. At 3 months follow-up, uterine artery PI was significantly higher (P<0.01) than the basal value in both group B (1.70+/-0.22-->1.88+/-0.16) and C (1.59+/-0.28-->1.92+/-0.21). The baseline PI values in group B1 and C1 were significantly higher than the baseline values observed in group B2 and C2 (1.76+/-0.17 vs. 1.32+/-0.02, 1.76+/-0.16 vs. 1.24+/-0.08) and significantly lower than those observed in group A (2.39+/-0.47). After 3 months of HRT, the PI values were not significantly higher than the baseline values in groups B1 and C2 (1.76+/-0.17-->1.90+/-0.17; 1.24+/-0.08-->1.74+/-0.16), while they were significantly higher in group C1 (1.76+/-0.16-->2.01+/-0.17). CONCLUSIONS: Sequential continuous HRT does not increase the volume of the uterine myoma. The findings of very low resistance index in the uterine arteries of women with growing myoma may indicate the risk of growth of the neoplasia during HRT. The assessment of PI in the uterine arteries could be helpful in predicting the growth rate of the myomas before starting HRT.     

Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined regimens

Compliance with hormone replacement therapy (HRT) is notoriously low despite ample documentation of clinical efficacy. The two major reasons given by women who discontinue HRT are uterine bleeding and side-effects. The recent development of a controlled and sustained vaginal progesterone gel allowed single daily application and made prolonged use such as for menopause possible. Here we report our clinical experience with two therapeutic options for HRT using natural progesterone administered vaginally. A first group of 69 menopausal women received the sustained release vaginal progesterone gel, Crinone 4% (45 mg daily) from days 1-10 of each calendar month with oestrogens taken continuously. A second group of 67 women received Crinone 4% twice weekly in conjunction with continuous oestrogen therapy. Endometrial thickness was evaluated before and after 6 months of treatment. Histological verification was obtained in all cases of abnormal bleeding. At 6 months, 63 out of 69 (91.9%) women receiving progesterone cyclically experienced predictable withdrawal bleeding. The vast majority, 54 (80.6%) of 67 women receiving Crinone in constant combined association with oestrogen therapy, remained amenorrhoeic throughout 6 months of therapy. All cases of abnormal bleeding were biopsied and no hyperplasia was seen. Our results indicate that both regimens using the sustained release vaginal progesterone gel controlled bleeding in HRT. Combined with the lower incidence of side-effects characteristic of vaginal progesterone, both vaginal progesterone regimens have the potential of improving HRT compliance.     

Successful treatment of infertile women with hypothalamic primary and secondary protracted amenorrhoea using gonadotrophin releasing hormone analogue and human menopausal gonadotrophin

Thirty-one women with hypothalamic primary or protracted secondary amenorrhoea were treated with human menopausal gonadotrophin (HMG) in 89 cycles, but adequate follicular growth failed to occur. They were then treated with a gonadotrophin releasing hormone analogue (GnRHa) and HMG in 91 cycles. An adequate ovarian response occurred in 68 cycles (74.7%) and pregnancy occurred in 26 cycles (28.6%). GnRHa and HMG produced an adequate ovarian response in hypothalamic amenorrhoeic patients who failed to respond to HMG alone. The strong initial agonistic effect of GnRHa produced sudden high levels of FSH that might possibly have initiated folliculogenesis which was continued by HMG.     

Low-dose danazol after combined surgical and medical therapy reduces the incidence of pelvic pain in women with moderate and severe endometriosis.

The most effective therapy for endometriosis is a matter for debate. The aim of the present randomized study was to evaluate the efficacy of low doses of danazol on recurrence of pelvic pain in patients with moderate or severe endometriosis, who had undergone laparoscopic surgery and 6 months of gonadotrophin-releasing hormone analogue (GnRHa) therapy. After surgery, 28 patients with moderate or severe endometriosis underwent therapy for 6 months with GnRHa i. m. every 4 weeks. They were then randomized into two groups: group A (14 subjects) was treated with 100 mg/day danazol for 6 months; group B (14 subjects, control) did not receive any type of therapy. After 12 months of treatment, group A had a significantly (P < 0.01) lower pain score than group B. There was no significant difference between the groups in oestrogen concentrations, bone mineral density or side-effects. The results suggest that low-dose danazol therapy reduces recurrence of pelvic pain in patients with moderate or severe endometriosis, treated surgically, and has few or no metabolic side-effects.     

Relationship of myoma cell size and menopausal status in small uterine leiomyomas

CONTEXT: Although myomas shrink after menopause, the cellular mechanism for this phenomenon has received little attention. It was recently demonstrated that fibrous degeneration is significantly associated with postmenopausal status in both small and large myomas. OBJECTIVE: The purpose of the present study was to evaluate whether reduction in myoma cell size is also associated with postmenopausal status in small myomas. DESIGN: Tumor size and patient age have also been related to fibrous degeneration in small (<1 cm) myomas. Therefore, in the present study, 10 pairs of premenopausal and postmenopausal small myomas were matched within 3 years for patient age, within 1 mm for size, and within 1 grade for degree of fibrous degeneration. Most of the women were in their 50s, the decade during which postmenopausal fibrous degeneration in small myomas is most prevalent. Myoma cell size was derived by morphometric evaluation of relative myoma cell area (correcting for percentage of stroma, as measured by point counting) and by direct counting of the number of myoma cells per unit area in trichrome-stained sections. RESULTS: Small myomas from postmenopausal women had significantly (P <.05) smaller cell sizes than did size-matched myomas from age-matched premenopausal women. Myoma cell sizes and nucleus-cell (N/C) ratios were highly variable, especially in premenopausal myomas. CONCLUSIONS: Reduction in myoma cell size is significantly associated with postmenopausal status in small uterine leiomyomas and may be an important mechanism for postmenopausal shrinkage of myomas. In addition, the high variability of myoma cell size and N/C ratio may further support the somatic mutation theory (ie, the theory that diverse mutations may account not only for variations in the growth potential of uterine myomas, but also for variations in their cellular details).     

Comparison of the Inhibitory Effect of Gonadotropin Releasing Hormone (GnRH) Agonist,Selective Estrogen Receptor Modulator (SERM), Antiprogesterone on Myoma Cell Proliferation In Vitro

Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.     

Potential role for medroxyprogesterone acetate as an adjunct to goserelin (Zoladex) in the medical management of uterine fibroids.

Twenty women with symptomatic uterine fibroids were treated with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin (Zoladex) combined with medroxyprogesterone acetate (MPA) in an open pilot study comparing two protocols. Ten women received goserelin 3.6 mg monthly combined with oral MPA 15 mg daily for 6 months. The mean uterine volume (497 cm3) measured by ultrasound fell by only 18% after 3 months, with no further reduction at 6 months. The other 10 women received goserelin alone for the initial 3 months, followed by combined treatment for 3 months. The mean uterine volume (557 cm3) fell by 39% after 3 months with no significant regrowth by 6 months. At 6 months post-treatment, uterine volume had not returned to pretreatment size. MPA significantly reduced the frequency of vasomotor side-effects. There were no differences in plasma oestradiol, luteinizing hormone or follicle stimulating hormone concentrations between the protocols and good symptomatic relief was experienced by both groups. Two years after completion, three women in each group have requested surgical treatment. The results indicate that MPA may be a useful adjunct to LHRH analogues in women with fibroids, reducing side-effects and possibly prolonging the response, although positive effects on bone density have yet to be confirmed. The optimum regimen of administration remains to be clarified as the clinical results were the same with both protocols.     

Influence of vaginal danazol on uterine and brain perfusion during hormonal replacement therapy.

OBJECTIVE: To evaluate the effectiveness of vaginal danazol as progestin supplement to estrogen replacement therapy, and its interference with uterine and carotid artery flow compared with medroxyprogesterone-acetate (MPA), estrogen alone, and placebo. METHODS: Forty healthy women at least 12 months after natural menopause were randomly divided into four treatment groups: Group 1 (n=10), continuous transdermal estradiol (TE) (50 microg/day), plus a monthly 10-day course of MPA (10 mg/day); Group 2 (n=10), continuous TE plus a monthly 10-day course of vaginal danazol (200 mg/day); Group 3 (n=10), TE alone; Group 4 (n=10), placebo. At baseline and during the first, third, and sixth month of treatment, the endometrial thickness was assessed by transvaginal ultrasonography, while the pulsatility index (PI) of the carotid and uterine arteries was assessed by color Doppler. An endometrial biopsy was also performed before and after the treatment. RESULTS: At baseline, no significant differences between ages and other evaluated parameters were present in the four groups. In groups 1, 2, and 3, the values of carotid and uterine PI decreased significantly and similarly during the treatment, while in group 4 they were unchanged. In group 3 only, the endometrium was significantly thicker during treatment than before. No endometrial hyperplasia was present in the four groups at the end of the treatment. CONCLUSIONS: Vaginal danazol seems to be capable of counteracting the mitogenic effect of estrogen on the endometrium without reducing the effectiveness of estrogens to improve peripheral arterial perfusion.     

Pregnancy following treatment of symptomatic myomas with laparoscopic bipolar coagulation of uterine vessels

BACKGROUND: Laparoscopic bipolar coagulation of uterine vessels (LBCUV) has been employed for women with symptomatic uterine myomas, but its effect on subsequent pregnancy has not been characterized. METHODS: Four-hundred and twenty-three women entered the study between March 1999 and December 2001. Of these, 142 women (33.6%) were under the age of 40 years at the time of LBCUV, 36 of whom (36/142, 25.3%) were sexually active without contraception. In a prospective study of 142 patients (<40 years old) undergoing LBCUV for symptomatic myomas, 15 women became pregnant (17 total pregnancies) and were evaluated by physical and ultrasound examinations. RESULTS: The volume of the dominant myoma was 117.4 +/- 118.4 and 36.8 +/- 56.8 cm(3) before and after LBCUV respectively. Volume of the dominant myoma after pregnancy was 46.2 +/- 76.7 cm(3) (mean +/- SD). There was a significant difference in myoma volume before and after LBCUV (P = 0.002), but no significant difference in myoma volume when comparing post-partum size with post-LBCUV size (P = 0.269). Pregnancy outcomes included seven miscarriages in the first trimester and one premature rupture of membrane (PPROM). Although the other pregnancies were regarded as uncomplicated, only two women were delivered of normal neonates as the other seven pregnancies were terminated secondary to patient request. CONCLUSIONS: The pregnancy and term pregnancy rates in sexually active women without contraception were 41.6% (15/36) and 5.6% (2/36) respectively. Because a relatively high rate (7/17, 41.2%) of early miscarriages was observed, we recommend that this procedure be employed only for women who do not desire additional children.     

Uterine endometrial thermal balloon therapy for the treatment of menorrhagia: long-term multicentre follow-up study

BACKGROUND: Initial reports from observational and randomized trials of uterine endometrial thermal balloon therapy (UBT) suggested good results as judged by return to eumenorrhoea or less and patient satisfaction. Long-term follow-up data remained limited by the small numbers of patients and duration of follow-up. We present long-term (4-6 years) follow-up data from a cohort of women previously treated with UBT for menorrhagia. METHODS: Of the 260 questionnaires sent to women eligible for long-term follow-up from 10 centres, 188 (72%) replies were received. The primary outcome measure was avoidance of hysterectomy. RESULTS: In women who responded to the questionnaire, 25 had undergone hysterectomy and 21 had had repeat ablation. At 4-6 years after UBT, the probability of avoiding hysterectomy was 86% of all women, and of avoiding re-ablation was 88% of non-hysterectomized women. Overall, the probability of avoiding any surgery was 75%. Women with an axial or retroverted uterus were at greater risk of hysterectomy or re-ablation. Among the participants, 47% of the non-hysterectomized women were amenorrhoeic, 30% were hypomenorrhoeic, 13.6% were eumenorrhoeic and 8.5% had heavy periods. CONCLUSIONS: This is the first long-term follow-up report of a second-generation endometrial ablation procedure and confirms our initial experience. The high rate of hysterectomy avoidance over 5 years or more is very encouraging for this technology.     

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

The aim of this study was to evaluate the effects of low-dose tibolone therapy on ovarian area, uterine volume and endometrial thickness, and define the cut-off value of endometrial thickness for curettage during uterine bleeding. We followed 619 postmenopausal women, aged 40-60 years, for two years. There were 301 subjects in the low-dose tibolone treatment group and 318 subjects in the control group. The ovarian area, uterine volume and endometrial thickness in all participants were measured by transvaginal ultrasound prior to, one and two years post enrollment, respectively. Endometrial specimens were collected from all subjects with abnormal uterine bleeding during the follow-up period. We found that the uterine volume in the treatment group was greater than that in the control group, and the difference was significant (P<0.05), but there were no significant differences in ovarian area and endometrial thickness between the two groups (P>0.05). When the cut-off value for endometrial thickness was 7.35 mm, the sensitivity and specificity were 100% and 79.07%, respectively, and 85.71% and 93.02% when 7.55 mm was set as the cut-off during tibolone therapy. The results indicate that low-dose tibolone therapy may postpone uterine atrophy and the cut-off value of endometrial thickness may be appropriately adjusted for curettage.     

Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis

Danazol is routinely administered orally to inhibit ovulation and to treat pelvic endometriosis. However, recent evidence suggests that danazol can act directly on endometriotic tissue in vitro to inhibit DNA synthesis and induce apoptosis. Danazol was administered via the vagina in this study, using a vaginal ring drug delivery system containing 1500 mg of danazol. This therapy was effective for treatment of pelvic endometriosis, especially for deeply infiltrating endometriosis, resulting in a cure of dysmenorrhoea and tenderness in the cul-de-sac within 3 months, and of induration or nodularity in the cul-de-sac within 7 months. Moreover, conception was possible during insertion of the vaginal ring in 17 out of 31 infertile women with deeply infiltrating endometriosis, and in two out of eight infertile women with ovarian endometriotic cysts not adhering to the cul-de-sac and without deeply infiltrating endometriosis. Serum danazol concentrations, high during oral daily 400 mg danazol therapy, but undetectable during vaginal danazol ring therapy, explain why ovulation and conception could occur during insertion of the vaginal danazol ring, and why general side-effects, which are often observed during oral danazol therapy, were not observed during vaginal danazol ring therapy. Danazol seems to be absorbed through the vaginal mucosa and reaches the deeply infiltrating endometriosis via diffusion.