Treatment Of Uterine Leiomyomas Research Articles

Embolisation of uterine arteries or laparascopic uterine artery ligation as possible treatment of uterine leiomyoma

Many women with symptomatic uterine leiomyomata wish to preserve their uterus. Novel organ- and fertility-preserving treatment options such as embolisation of uterine arteries or laparascopic uterine artery ligation have frequently been discussed as viable alternatives to myomectomy. This article strives to bring together the conclusions of major studies on novel organ-preserving treatment alternatives for uterine myoma. Minimally invasive organ-preserving laparascopic myomectomy remains the best treatment option for patients with symptomatic fibroids who wish to retain their uterus. However, in certain cases other options such as embolisation or laparascopic ligation of uterine arteries can serve as viable alternatives A failure rate of up to 39% and complications such as reduced fertility because of ovarian failure after transcatheter embolisation of uterine arteries might restrict the use of this method. For postmenopausal women, transcatheter embolisation of uterine arteries is a possible treatment alternative. Laparascopic ligation of uterine arteries and anastomotic sites of uterine arteries with ovarian arteries might also be viable for young women who desire to preserve future fertility. Further data and studies on the long-term follow-up after ligation are yet to come.

Evidence for a Modulation of Apoptosis by Recombinant Human Choriogonadotropin (r-hCG) in Uterine Leiomyoma Cell Cultures

Uterine Leiomyome sind die häufigsten gutartigen Neoplasien der Frau. Ihr Wachstum wird durch Östradiol und Progesteron gefördert. Im Schwangerschaftverlauf zeigen die meisten Leiomyome trotz hoher Steroidkonzentrationen kein signifikantes Wachstum. Dies könnte auf eine Induktion des programmierten Zelltods durch Apoptose durch das Choriogonadotropin des Menschen (hCG) zurückzuführen sein, wie sie für andere Zellarten gezeigt werden konnte. HCG/LH-Rezeptoren werden von Leiomyomen exprimiert. In dieser Arbeit wurde deshalb untersucht, ob hCG einen direkten Einfluss auf die DNA-Fragmentierungsrate in der Leiomyomzellkultur hat.

Coil Embolization of a Tuboovarian Anastomosis before Uterine Artery Embolization to Prevent Nontarget Particle Embolization of the Ovary

Uterine artery embolization (UAE) is being used more frequently as a primary treatment for uterine leiomyoma. Performing UAE in women who desire future fertility is controversial because of the risks of premature menopause and the undetermined effects on pregnancy. The etiology of ovarian failure after UAE is not yet clearly defined, but one of the leading possibilities is nontarget embolization of the ovaries. In this case report, the authors describe a technique of selective coil embolization of a uterine artery-to-ovarian artery communication before UAE performed specifically to protect the ovary from nontarget embolization.

Focused ultrasound treatment of uterine fibroid tumors: Safety and feasibility of a noninvasive thermoablative technique

Objective: The purpose of this study was to determine the safety and efficacy of focused ultrasound surgery with magnetic resonance imaging guidance for the noninvasive treatment of uterine leiomyomas. Study Design: Fifty-five women with clinically significant uterine leiomyomas were treated. Pain and complications were assessed prospectively, and posttreatment magnetic resonance imaging was used to measure the treatment effects. Patients in three of the five centers underwent planned hysterectomy after treatment, which provided pathologic correlation of treatment. Results: Seventy-six percent of the enrolled patients completed the full treatment session. All treatments were conducted in an outpatient setting with minimal discomfort for subjects and no major complications. Pathologic examination of the uterus confirmed that magnetic resonance imaging guidance provides the safe and accurate delivery of effective levels of thermal energy with a 3-fold increase in volume of histologically documented necrosis, compared with treatment volume (6.6 ± 0.8 vs 18.4 ± 3.9 mL, P <.005). Conclusion: Magnetic resonance imaging-guided focused ultrasound surgery appears to be a well-tolerated treatment for uterine leiomyomas. (Am J Obstet Gynecol 2003;189:48-54.)

Pregnancy after uterine artery embolization

BACKGROUND: Uterine artery embolization is an increasingly popular alternative to hysterectomy and myomectomy as a treatment for uterine leiomyoma. Whether this procedure is safe for women desiring future fertility is controversial. CASES: A primigravida who had previously undergone uterine artery embolization had premature rupture of membranes at 24 weeks. She had a cesarean delivery at 28 weeks, which was followed by uterine atony requiring hysterectomy. A primigravida who had previously undergone uterine artery embolization delivered appropriately grown dichorionic twins at 36 weeks. An analysis of the 50 published cases of pregnancy after uterine artery embolization revealed the following complications: malpresentation (17%), small for gestational age (7%), premature delivery (28%), cesarean delivery (58%), and postpartum hemorrhage (13%). CONCLUSION: Women who become pregnant after uterine artery embolization are at risk for malpresentation, preterm birth, cesarean delivery, and postpartum hemorrhage.

Pregnancy After Uterine Artery Embolization

In Brief BACKGROUND Uterine artery embolization is an increasingly popular alternative to hysterectomy and myomectomy as a treatment for uterine leiomyoma. Whether this procedure is safe for women desiring future fertility is controversial. CASES A primigravida who had previously undergone uterine artery embolization had premature rupture of membranes at 24 weeks. She had a cesarean delivery at 28 weeks, which was followed by uterine atony requiring hysterectomy. A primigravida who had previously undergone uterine artery embolization delivered appropriately grown dichorionic twins at 36 weeks. An analysis of the 50 published cases of pregnancy after uterine artery embolization revealed the following complications: malpresentation (17%), small for gestational age (7%), premature delivery (28%), cesarean delivery (58%), and postpartum hemorrhage (13%). CONCLUSION Women who become pregnant after uterine artery embolization are at risk for malpresentation, pre-term birth, cesarean delivery, and postpartum hemorrhage. Pregnancy complications after uterine artery embolization include malpresentation, preterm birth, cesarean delivery, and postpartum hemorrhage.

Technical success rate of uterine artery embolisation for treatment of uterine leiomyomas at the University of the Free State

The technical success rate of uterine artery embolisations at the Department of Diagnostic Radiology, University of the Free State (UFS) is reported. From November 1998 to July 2001, 67 women, aged 35 - 75 years, received uterine artery embolisation. The procedure was usually performed through a single 4-French sheath set which was introduced into the right femoral artery using a 4- French catheter and injecting PVC particles (150 - 550 micron). Embolisation was performed successfully in 85.5% of the women. The mean total fluoroscopy time was 16.8 minutes, ranging from 4.8 minutes to 47.3 minutes.

Prediction of the effects of gonadotropin-releasing hormone agonist therapy in uterine leiomyoma by T1 contrast-enhanced magnetic resonance imaging sequences

Uterine leiomyomas occur in 20% of women of reproductive age and often cause symptoms, including prolonged or heavy menstrual bleeding, pelvic pressure or pain, infertility, or spontaneous abortion (1). Gonadotropin-releasing hormone (GnRH) agonists are a popular treatment for uterine leiomyomas because they decrease uterine blood loss due to myomas and the volume of the myomas themselves. However, after cessation of GnRH agonist therapy, the myomas return to their original size. Thus, surgical resection remains the mainstay of treatment.

Role of hormonal and reproductive factors in the etiology and treatment of uterine leiomyoma.

Uterine leiomyomas are the most common gynecologic neoplasm in reproductive-age women. While it is clear that hormonal factors play a prominent role in this disease, how steroid hormones contribute to disease etiology or may be utilized as targets for intervention are currently areas of active scientific investigation. To study the impact of hormones on uterine leiomyomas, the Eker rat has been developed as an in vivolin vitro animal model system for these tumors. Spontaneous leiomyomas arise in intact Eker rats with a high frequency and leiomyoma-derived cell lines from these animals maintain the biochemical and physiological characteristics of the tumors from which they were obtained. Using this animal model system, it has been established that tumor development is absolutely dependent on steroid hormones and that sensitivity/responsiveness to estrogen is enhanced in tumors and tumor-derived cell lines. Modulation of hormonal milieu, such as that which naturally occurs during pregnancy, can effectively inhibit tumor development. The hormone responsiveness of these tumors makes them good candidates for hormonal therapy. Selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene hold promise as potential therapeutic agents for this disease. SERMs inhibit proliferation of leiomyoma-derived cell lines in vitro, repress the growth of these lines in nude mice, and, when administered over a 2- to 4-month course of treatment to Eker rats, reduce tumor incidence by more than 50%. In addition to endogenous hormones, xenoestrogens in our environment (e.g., phytoestrogens, organochlorine pesticides, pharmacologic compounds) are of potential concern with regards to their impact on this disease. These environmental estrogens have been shown to promote the growth of leiomyoma cells in vitro and in vivo. Further elucidation of the role of these and other hormonal and reproductive factors in the development of uterine leiomyoma will be invaluable for increasing our understanding of the etiology of this disease and developing new therapeutic strategies to help to reduce the negative impact of uterine leiomyomas on women's health.

A benefit-risk assessment of medical treatment for uterine leiomyomas.

The growth of a uterine leiomyoma growth stops and regresses after the menopause suggesting that leiomyoma growth is dependent on ovarian steroids. Therefore, estrogen has received much attention as the major factor responsible for the development of uterine leiomyomas, but progesterone also plays an important role in development of this disease. Cytogenetic analyses of resected samples has revealed that about 40 to 50% of leiomyomas show karyotypically detectable chromosomal abnormalities. Gonadotrophin releasing hormone (GnRH) agonists exert their action through the suppression of endogenous gonadotrophins and gonadal steroid secretion. Significant reductions of uterine/leiomyoma volume under GnRH agonist therapy has been reported in several studies. However, the leiomyoma generally returns to its pretreatment volume within a few months after discontinuation of the GnRH agonist. To minimise the adverse effects of hypoestrogenism during GnRH agonist treatment, add back therapy can be used (estrogen-progestin, progestin alone and recently tibolone). Antiprogestins have a potential clinical utility in uterine leiomyomas. Mifepristone is a synthetic steroid with both antiprogesterone and antiglucocorticoid activities, that may have an inhibitory effect on growth of leiomyoma. Danazol is an isoxazole of 17beta-ethinyl testosterone, a synthetic steroid, which has a suppressive effect on sex hormone binding globulin concentrations, resulting in efficacy in the short-term treatment of uterine leiomyomas. Gestrinone is a tri-enic steroid with antiestrogen and antiprogesterone properties and has been shown to reduce uterine volume and stop bleeding. Growth factors play a relevant role on the pathophysiology of uterine leiomyoma and probably the inhibition of the action of growth factors on the myometrium will be the basis for future therapy. A number of agents are under investigation for treating uterine leiomyoma. Agents developed from increasing genetic knowledge of this condition could represent, in the next few years, new trends in the medical treatment of uterine leiomyomas.

Effects of gonadotropin-releasing hormone analog treatment on skin condition

The skin is a target organ of estrogens. Thus, theoretically, a hypoestrogenic state induced by gonadotropin-releasing hormone analog (GnRHa) treatment may have effects on skin condition. The aim of thisstudy was to evaluate skin condition during GnRHa treatment. Sixteen premenopausal women undergoing GnRHa treatment for 16 weeks, as a presurgical treatment for uterine leiomyomas, were studied. Measurementof serum estradiol levels and epidermal hydration, and evaluation of subjective findings on skin condition using a questionnaire, were performed every 4 weeks during the treatment period. Serum estradiollevels were significantly suppressed at 4 weeks of treatment, and remained low afterwards. Epidermal hydration measured by corneometer did not show any significant difference at any time point examined,compared with that before treatment. No particular subjective findings relating to the skin (dryness, wrinkling, roughness, pigmentation, itching, formication, reaction to cosmetics) were reported duringtreatment, whereas complaints about hot flushes and sweating were notable. The results of this preliminary study support the notion that GnRHa treatment for 16 weeks is unassociated with apparent changesin skin condition.

Uterine arterial embolization for the treatment of uterine leiomyomas.

The purpose of this study was to establish guidelines for using uterine artery embolization for the treatment of uterine leiomyomas accompanied by adenomyosis in Korea. This study was performed to investigate 1) the effects of uterine embolization on leiomyoma accompanied by adenomyosis, 2) the outcome of uterine embolization according to the embolization materials used, 3) the relationship between the Resistance Index (RI) and the change in uterine volume. We performed a retrospective study on 37 women who had uterine leiomyomas accompanied by adenomyosis. Bilateral uterine artery embolization was performed over a period of 17 months in 37 patients (age range 25 - 65) experiencing pain, hypermenorrhea, urinary frequency, etc. due to leiomyomas. Ultrasound imaging was performed before the procedure and at mean 6.9 months after the procedure. All procedures were technically successful. Mean clinical follow-up time was 12.8 months. Minor complications occurred in 82% patients following the procedure. After follow-up imaging, the median uterine volume decreased by 34.4% and the dominant myoma volume decreased by 86%. There was no statistical difference in the uterine volume reduction and the dominant myoma size reduction, whether the occluding agent was polyvinyl alcohol, polyvinyl alcohol plus gelfoam, or gelfoam, and whether the ultrasound measured Resistance Index value before the procedure was low or high. Primary candidates for uterine artery embolization include those with symptomatic uterine leiomyomas, who no longer desire fertility, but who wish to avoid surgery or are poor surgical risks. According to the results of our study, adenomyosis should not be considered as a contraindication for uterine artery embolization. However, because little data is available about the subsequent reproductive potential following this procedure, it should not be routinely advocated for infertile women. Further investigation is warranted regarding the choice of occluding agent and the role of the Resistance Index.

Leiomyomata treated with uterine artery embolization: factors associated with successful symptom and imaging outcome.

To determine whether baseline variables are associated with treatment success after uterine artery embolization for treatment of uterine leiomyoma. Two hundred consecutive patients who underwent uterine artery embolization at one institution were prospectively examined. Baseline clinical variables measured included age, race, prior oral contraceptive use or progesterone treatment, prior gonadotropin-releasing hormone agonist treatment, and prior births. Imaging parameters were baseline uterine volume, baseline leiomyoma volume and location, and number of leiomyomas. After treatment, follow-up imaging and questionnaire data were obtained at 3 and 12 months. Associations between baseline characteristics and outcome variables of interest were assessed by using linear regression, logistic regression, Pearson product moment correlation coefficients, and Kendal tau correlation coefficients, with adjustment for confounding variables when indicated. Regression models indicated that larger dominant leiomyoma volume was associated with a smaller percentage reduction in volume at 3 months (P =.03). A submucosal leiomyoma location was associated with a greater volume reduction at 3 months (P =.04), but this difference did not persist at 12 months (P =.09). The odds of reported menstrual bleeding improvement at 3 months were higher with a submucosal leiomyoma location (P =.04); however, this association was not statistically significant after adjustment (P =.07). The odds of improved bulk-related symptoms were not associated with leiomyoma volume change or location. Smaller baseline leiomyoma size and submucosal location are more likely to result in a positive imaging outcome. There are limited associations between other baseline parameters and either symptom change or imaging outcome.

An in vivo/in vitro model to assess endocrine disrupting activity of xenoestrogens in uterine leiomyoma.

Xenoestrogens with endocrine disrupting activity have been associated with the dysregulation of reproductive function and promotion of malignancies in experimental animals and human populations. The high incidence of uterine leiomyomas, a benign estrogen-responsive neoplasm of the uterine myometrium, calls into question the potential influence of xenoestrogens in the pathogenesis of these tumors. An in vivo/in vitro animal model, the Eker rat, that can be used to assess the estrogen-like agonist activity of potential endocrine disruptors in the uterine myometrium is discussed. Using this model, several in vitro assays are developed that demonstrate that compounds from three major classes of xenoestrogens can mimic the effect of estrogen on leiomyoma cells and act as estrogen receptor (ER) agonists: phytoestrogens, organochlorine pesticides and pharmacologic agents. These compounds can stimulate transcription via the ER and upregulate the expression of an estrogen-responsive gene in uterine leiomyoma cells. The use of these in vitro assays has also advanced our ability to predict the agonist activity of potential therapeutic agents in the uterine myometrium. Selective estrogen receptor modulators (SERMs), while able to act as agonists in some tissues such as the bone and uterine endometrium, act as antagonists in vivo in the uterine myometrium and in our in vitro assays. This antagonist activity in the uterine myometrium suggests that SERMs may be useful in the treatment of uterine leiomyoma.

Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate.

We have shown that in situ estrogen synthesized in leiomyoma of the uterus plays a possible role in the promotion of leiomyoma cell growth via an autocrine/paracrine mechanism. In the present study, we demonstrated that leuprorelin acetate, a GnRH agonist widely used for treatment of uterine leiomyoma by down-regulation of pituitary-ovarian function, suppressed the expression of aromatase P450 (an estrogen synthetase) in leiomyoma cells. Given the role of in situ estrogen in leiomyoma cell growth, the inhibition of in situ estrogen synthesis may play a role in GnRH agonist-induced rapid regression of leiomyomas. Quantitative RT-PCR revealed that in women receiving no medication uterine leiomyomas express aromatase P450 mRNA at levels 20 times higher than that in the surrounding myometrium. Leuprorelin acetate treatment (1.88 mg every 4 wk, sc injection) for 12-24 wk reduced the expression of aromatase P450 mRNA in leiomyoma tissue as well as in the myometrium, to approximately one tenth of that in the myometrium of untreated women. Suppression of aromatase P450 expression was also demonstrated by Western blot analysis and aromatase activity assay of microsomal fractions prepared from leiomyomas. On the other hand, no differences in the levels of activity and mRNA of aromatase P450 were observed between leiomyoma cells obtained from women treated with and without leuprorelin acetate injections when cells were cultured ex vivo and stimulated by various combinations of stimulants such as dexamethasone + IL-1beta. The addition of various concentrations of E2 did not affect the aromatase activity of leiomyoma cells, suggesting that deprivation of circulating (ovarian) estrogen is not a cause of decreased expression of aromatase during leuprorelin acetate therapy. On the other hand, 8-d treatment with leuprorelin acetate (100 nmol/liter) reduced dexamethasone + IL-1beta-induced activity and a mRNA level of aromatase by 28% and 42%, respectively. These results indicated that leuprorelin acetate inhibits the expression of aromatase P450 in leiomyoma cells, which contributes to the rapid regression of leiomyoma during leuprorelin acetate therapy.

Tratamento dos Leiomiomas por Embolização das Artérias Uterinas

Objetivos: avaliar os resultados da embolização das artérias uterinas (EAU) como tratamento do leiomioma uterino. Métodos: foram estudadas 18 mulheres com diagnóstico ultra-sonográfico de leiomioma uterino submetidas à EAU com partículas de álcool polivinílico (PVA). O acesso arterial foi realizado por punção da artéria femoral e a progressão do cateter foi monitorada até atingir seletivamente as artérias uterinas. A avaliação dos resultados foi realizada pelo estudo ultra-sonográfico antes e três meses após o procedimento. Foi realizado controle clínico evolutivo para avaliação das características menstruais e do volume uterino. Resultados: houve insucesso técnico em três casos por dificuldade de cateterização das artérias uterinas. O sangramento e a dismenorréia foram controlados no intervalo de três meses em 86 e 60% das pacientes, respectivamente. A média dos volumes uterinos iniciais foi de 381 cm³ e após 3 meses foi de 263 cm³. Houve redução média de 27,4% no volume uterino três meses após o tratamento. Três pacientes tiveram insuficiência ovariana clínica e laboratorial (20% dos casos). Conclusões: a EAU representa alternativa terapêutica para o tratamento dos leiomiomas uterinos. Em virtude do risco de insuficiência ovariana esse procedimento é reservado para pacientes com mais de 45 anos de idade ou com prole completa.

Outcome and resource use associated with myomectomy

OBJECTIVE: To evaluate the outcomes and cost of myomectomy through retrospective claims data analysis. METHODS: The study was performed using a retrospective database of private insurance claims from 1995 to 1997. Records were selected for analysis based on the presence of ICD-9-CM procedure and/or CPT-4 codes associated with myomectomy. In addition, diagnosis of uterine leiomyoma and related symptoms for these patients were confirmed through ICD-9-CM diagnosis codes. Inpatient, outpatient, and physician costs were estimated. All cost data were converted into 1997 dollars. RESULTS: A total of 4394 women, between the ages of 14 and 70, were available for analysis. Of these, 3305 were classified by type of myomectomy procedure, and complete data were available on 820 at 1 year and 236 at 2 years. Abdominal myomectomies were the most common procedures, followed by hysteroscopic and laparoscopic myomectomies. Conversion to a more invasive procedure occurred in 5.4% of the patients. The rate of additional surgeries was 8.3% in 6 months, 10.6% in 1 year, and 16.5% in 2 years. Overall cost increased from an initial $6,737 per patient to $7,575 in 1 year and to $8,001 in 2 years. CONCLUSION: The repeat procedures required after the initial myomectomy add significantly to total cost and highlight the importance of assessing post-procedure health care use. This comprehensive analysis facilitates the systematic evaluation of myomectomy with current and emerging alternative treatments for uterine leiomyomas.

Identification of new therapies for leiomyomas: what in vitro studies can tell us.

Leiomyomas are a significant problem in women's health. An understanding of the biology of these tumors and how their growth is regulated is emerging from in vitro studies using tissue specimens and cultured cells. These studies have clarified how the ovarian steroid hormones regulate growth of uterine SMCs and how the ovarian steroid ligand-receptor system has been altered in leiomyomas. Such information will allow investigators to identify steroid hormone antagonists and steroid hormone receptor modulators that may be useful for treatment of leiomyomas. We are now also developing a much better understanding of the growth factors that are produced by SMCs of leiomyoma tumors. These growth factors not only regulate the proliferation, apoptosis, and extra-cellular matrix production of the SMCs but also regulate proliferation and migration of vascular endothelial cells. Targeting these growth factors and their receptors can reduce leiomyoma growth through two different mechanisms. One targets the SMCs and the other targets the vascular system that supports the growth of the tumor. Another important lesson that can be learned from reading the scientific literature is that there are striking similarities between the biology of uterine leiomyomas and other pathologic diseases that involve mesenchymally derived cells. These include benign keloids, other fibrotic diseases such as pulmonary fibrosis, and vascular diseases such as atherosclerosis. Compounds that are developed to treat these conditions may also be beneficial for treatment of uterine leiomyomas. The next few years will undoubtedly yield many new drug discoveries for these diseases.

Clinical Study on Treatment of Uterine Leiomyoma with Different Dosages of Mifepristone

Objective To explore the therapeutic effect of treatment of uterine leiomyoma with different dosages of mifepristone and the effects of mifepristone on sex hormones.Methods The patients of uterine leiomyoma were divided into two groups,group A included 45 patients who were mifepristone orally given neoplasma,25mg per day for 3～6 months,group B included 30 patients who took mifepristone 12.5mg per day for 3～6 months.The size of uterus and uterine leicomyoma were detected with type B sonarography and serum sex hormones level were tested with radioimmunoassay before the treatment.Results Amenorrhea was found during the treatment of two groups and after tree months' the symptoms were improved,the size of uterine leiomyoma in group A was meanly decreased by 52.56% and 61.69% respectively,after six months' treatment;The size of uterine leiomyoma in group B was averagely decreased by 48.61% after three months' treatment and by 52.12% after six months' treatment.There was no significant difference between A and B group after three months' treatment(P＞0.05),But there was significant difference between the two groups after six months' treatment and it dependent on the time of the treatment.Contents of serum estradiol and progestagen of the two groups were droped dwon significantly after treatment(P＜0.01).Conclusions Mifepristone applied to treat the uterine leiomyoma have definitve therapeutic effect,and less side effects.Therefore,mifepristone provides a new avenue to treat uterine leiomyoma and suggesting its best dosage is 25mg every day.

Long-term administration of tibolone plus gonadotropin-releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass, and lipid profiles

Objective: To evaluate the effects of long-term administration of GnRH agonist (GnRH-a) plus tibolone for uterine leiomyomatosis. Design: Prospective open clinical trial. Setting: Department of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, University of Naples “Federico II”, Naples, Italy. Patient(s): Twenty-five subjects with symptomatic uterine leiomyomas. Intervention(s): Treatment for 2 years with leuprolide acetate (3.75 mg IM every 28 days) and tibolone (2.5 mg/d per os). Main Outcome Measure(s): Uterine and uterine leiomyoma sizes, endometrial thickness, lumbar spine bone mineral density (BMD), bone metabolism, lipid profile, myoma-related symptoms at baseline and every 6 months. Hot flashes and vaginal bleeding episodes recorded in a daily symptom diary. Result(s): After 6 months of treatment, a significant reduction was observed in uterine and leiomyoma volumes and myoma-related symptoms compared with baseline values. No significant change was observed in bone turnover, lumbar BMD, or serum total cholesterol, low-density lipoprotein cholesterol, or triglyceride levels. High-density lipoprotein cholesterol values were significantly lower than baseline values after 6 months of treatment but not after 18 months of therapy. A low mean number of hot flashes per day was observed. Conclusion(s): Long-term administration of GnRH-a plus tibolone reduces hot flashes and prevents bone loss without changing the lipid profile.