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.     

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.     

Long-term conservative therapy for endometrial adenocarcinoma in young women

BACKGROUND: To evaluate the efficacy and safety of long-term conservative therapy with medroxyprogesterone acetate (MPA) for endometrial carcinoma in young patients who had experienced failure after initial therapy or relapse, we reviewed the clinical and pathologic records of eight patients diagnosed with well-differentiated endometrial adenocarcinoma without myometrial invasion who were treated with MPA for over 6 months because of treatment failure or relapse. RESULTS: The average duration of MPA treatment was 22 months. All patients were followed-up for a mean of 76.5 months. Seven patients responded to initial MPA treatment within a period of 14 months (mean, 7.9 months). All these patients experienced relapse and the mean time to relapse was 11.6 months (range, 4-33 months). All six patients with relapse were treated with additional treatments of MPA, and all but one responded to this treatment within a period of 16 months (mean, 8.0 months). Six patients ultimately underwent hysterectomy. All presented well-differentiated endometrioid adenocarcinomas without extrauterine disease. Three became pregnant and two delivered full-term normal infants. No patient died of the disease. CONCLUSION: Although lesions are expected to disappear with prolonged MPA treatment, this form of progestin therapy is hazardous because recurrence occurs frequently. Only strictly selected patients should therefore be indicated for long-term MPA treatment and careful evaluation before and after treatment should be performed.     

A comparative study of the effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability

BACKGROUND: Hormone therapy (HT) after the menopause is associated with increased risk of venous thromboembolism (VTE). Tibolone has pharmacodynamic properties different from other hormone preparations. We compared the effect of a combined HT and tibolone on the inhibition of haemostasis. METHODS: Thirty-eight post-menopausal women were randomly assigned to 1.25 or 2.5 mg per day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Inhibitors of haemostasis were measured at baseline and after 12 months. RESULTS: Results from the two groups of women receiving tibolone were not significantly different and, to improve the power of the study, the two groups were merged. Higher concentration of protein S (1.16 versus 1.00 IU ml(-1); P = 0.005) and higher activated protein C resistance ratio (APC-R) (4.2 versus 3.65; P = 0.04) were observed in the tibolone group than in the CEE/MPA group. Both doses of tibolone increased APC-R significantly (P < 0.01). Tissue factor pathway inhibitor (TFPI) was lower in the CEE/MPA group than in the tibolone group (67.8 versus 79.9 ng ml(-1); P = 0.03). CEE/MPA reduced the concentration of antithrombin (P = 0.002), protein S (P < 0.001) and TFPI (P < 0.001). Both preparations reduced the concentration of plasminogen activator inhibitor 1 (P < 0.05). CONCLUSIONS: Tibolone induces fewer pharmacological alterations on blood coagulability than CEE/MPA and has a potentially favourable effect on APC-R. This may translate into a corresponding low risk of VTE, as also indicated from the existing clinical data.     

Megestrolazetat in verschiedenen Dosierungen bei der Behandlung des metastasierenden Mammakarzinoms — Klinische und endokrinologische Untersuchungen

Summary Both medroxyprogesterone acetate (MPA) and megestrol acetate (MA) are effective in the treatment of metastatic breast cancer. Although the dose-dependent mode of actions of MPA have been extensively clarified, there is still some uncertainty regarding the mode of actions and dosage of MA. Thirty-three patients with metastatic breast cancer were treated with various dosages of MA under a phase-II study. Eight patients were given 200 mg, 9×400 mg, 10×600 mg and 6×800 mg MA daily per os. The LH, FSH, TBI, T₃, T₄, TSH, ACTH, aldosterone, testosterone, prolactin and cortisol levels were determined regularly during treatment to enable the investigation of the pharmacodynamics of MA. A complete remission was achieved in two patients, a partial remission in seven patients and there was no change in eight patients (total responder rate 51.5%). The clinical and endocrine changes therefore suggest that the dose-dependent mode of actions of MPA and MA are identical. Equivalent dosages of MPA are 1000–1500 mg per os and of MA 160–200 mg. Furthermore, similar relationships between the endocrine changes and remission behaviour of MA and MPA have been observed. Persisting tumour remissions are inevitable under cortisol suppression and normal prolactin, aldosterone and ACTH levels.

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Abkürzungen CR komplette Remission - MA Megestrolazetat - MPA Medroxyprogesteronazetat - NC keine Veränderung - PD progrediente Erkrankung - PR partielle Remission     

Effects of medroxyprogesterone acetate on socio-sexual behavior of stumptail macaques

Two studies assessed (1) the effect of medroxyprogesterone acetate (MPA), Depo-Provera, on socio-sexual behaviors, and (2) the interaction between socio-environmental conditions and MPA treatment effects. Study One utilized two males and eight female members of a semi-free-ranging island colony. Females received 30 or 100 MPA IM or were untreated. Study Two used three laboratory-housed pairs of tubal-ligated females, observed during 30 min behavior tests with one of three males. Sexually preferred females received 30 mg MPA IM. Semi-free-ranging treated females received fewer ejaculations than untreated females and did not copulate for up to 68 days post-treatment. Rates of grooming were not affected. In the laboratory tests, mean rates of ejaculations per test were reduced for treated females but increased for untreated females, and untreated females groomed males more than did treated females. Contrary to previous studies, these results suggest that stumptail macaque sexual behavior can be influenced by hormones but this influence is modulated by socio-environmental factors.     

On the role of additive hormone monotherapy with tamoxifen,medroxyprogesterone acetate and aminoglutethimide,in advanced breast cancer

Summary We analyzed the results of clinical studies on the therapeutic efficacy of hormone monotherapy with tamoxifen, medroxyprogesterone acetate, and aminoglutethimide in metastatic breast cancer, which were published between 1971 and 1986 and involved altogether 7000 patients. The overall response rates in patients treated with these hormonal single agents at various dose levels ranged from 31%–42%. When only estrogen receptor-positive patients were considered, the response rates lay between 41% and 54% in groups which were treated with the antiestrogenic agents tamoxifen or aminoglutethimide. The duration of remission was 12 months for tamoxifen- and aminoglutethimide-treated women, whereas medroxy-progesterone acetate effected remissions lasting from 6–16 months. The overall mean survival from start of therapy in tamoxifen- and aminoglutethimide-treated groups was 20 months, whereas information concerning this therapeutic parameter was available only in a minority of medroxyprogesterone acetate-treated groups. With respect to the response by site of metastatic lesions, all three agents caused a significantly higher degree of remissions in the soft tissue as compared to visceral disease.Abbreviations AG Aminoglutethimide - MPA Medroxyprogesterone acetate - TAM Tamoxifen     

Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: A randomized comparative dose-ranging study

Objectives: We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E₂V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E₂) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study. Methods: 440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E₂V+2.5 mg MPA; 1 mg E₂V+5 mg MPA; or 2 mg of E₂+1 mg NETA. After the first 6 months, the E₂V dose was increased to 2 mg in both E₂V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits. Results: Significantly fewer bleeding days were experienced in the first 3 months by women taking E₂V/MPA compared with women taking E₂/NETA. When the dose of E₂V was increased in the E₂V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E₂/NETA group compared with either of the E₂V/MPA groups. The overall continuation rates ranged from 70 to 86%. Conclusions: These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E₂V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT.     

The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial

BACKGROUND: Among patients using GnRH analogues for endometriosis it has been postulated that peripheral and inflammation-induced in-situ aromatization of adrenal androgens are probably the main reasons for the high rates of failure during follow-up. We hypothesized that in cases with premenopausal severe endometriosis, use of a combination of anastrozole and goserelin to achieve almost maximal endocrine blockade of estrogen synthesis after conservative surgery may increase the pain-free interval and reduce the recurrence rates as compared to goserelin alone. METHODS: In a prospective randomized trial, we evaluated the efficacy of using either a combination of anastrozole and goserelin for 6 months or goserelin alone for 6 months after conservative surgery for severe endometriosis. The primary outcome measures were the symptom recurrence rates and the impact of treatment on endometriosis-related multidimensional score. The secondary outcome measures were the impact of allocated treatment regimens on menopausal quality of life and on lumbar spine bone mineral density (BMD). RESULTS: When we analyzed the Kaplan-Meier survival curves, we detected a statistically significant advantage of goserelin plus anastrozole as compared to goserelin only, in terms of the median time to detect symptom recurrence (>2.4 versus 1.7 months; log-rank test; P=0.0089). This statistically significant advantage occurred with a relative risk of 4.3 [95% confidence interval (CI) 1.3-9.8]. Three cases out of 40 recurred in the goserelin plus anastrozole arm (7.5%), whereas we detected recurrences in 14 cases out of 40 cases in the goserelin-only arm (35%) during the follow-up period of 24 months. Based on these data, the interpretation of Kaplan-Meier curves indicates that at the end of follow-up, 54.7 versus 10.4%, respectively, of the patients were free of recurrence. The mean of the differences in terms of Deltabaseline-24 months post-medical therapy multidimensional score were statistically significant in favour of goserelin and anastrozole (9.2 +/- 2.1 versus 6.7 +/- 2.8; paired t-test; P<0.0001; 95% CI 1.5-4.0). We observed a statistically significant difference in suppression of estradiol concentrations and a significantly greater BMD loss at the end of treatment in the goserelin and anastrozole arm as compared to goserelin-only arm. However, this did not elicit deterioration in menopausal quality of life and the observed bone loss was not significant in terms of DeltaBMD between the groups at 2 years of treatment withdrawal. CONCLUSIONS: Six months of treatment with anastrozole and goserelin as compared to goserelin alone increased the pain-free interval and decreased symptom recurrence rates in patients following surgery for severe endometriosis. Furthermore, menopausal quality of life and BMD at 2 years after medical therapy remained unaffected.     

Endocrinology: Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study

One-hundred women undergoing ovarian stimulation with gonadotrophin-releasinghormone agonist (GnRH-a) and a human menopausal gonadotrophin(HMG) for in-vitro fertilization (IVF) participated in thisrandomized comparative study. The effectiveness of long-actings.c. goserelin (Zoladex depot; 49 patients) and intranasally(i.n.) administrated buserelin acetate (Suprefact; 51 patients)for pituitary down-regulation was compared. Treatment with s.c.goserelin (3.6 mg) or i.n. buserelin acetate (200 µg;6 times/day) was started on day 21–23 of the cycle. Stimulationwith 150 IU of HMG/day was started after at least 11 days ofGnRH-a treatment. There were no differences in the time requiredfor follicular development nor in the clinical outcome betweengroups treated with either goserelin or buserelin. The numberof oocytes recovered in the goserelin group was 6.7 ±5.0 versus 6.3 ± 4.9 in the buserelin group. There were11 pregnancies after the use of goserelin (22.4%) and 12 pregnanciesin those given buserelin (24.0%). The number of HMG ampoulesneeded for follicular maturation was higher in the goserelingroup (27.9 ± 7.8) than in the buserelin group (24.6± 7.8, P < 0.05). The patients given buserelin sufferedsignificantly more from tiredness, depression, headache andabdominal pain than those receiving goserelin, whereas therewere no differences between the groups in experiencing mentalirritability, nausea and swelling. Subcutaneous goserelin depotinjection offers a useful alternative for pituitary down-regulationin IVF stimulation.     

Progestin stimulates the biosynthesis of fibronectin and accumulation of fibronectin mRNA in human endometrial stromal cells.

Fibronectin is a major component of decidual basement membrane. In the present study, we have investigated the effect of progestin on the synthesis and secretion of fibronectin in human endometrial stromal cells. Stromal cells were isolated during the menstrual cycle and cultured in RPMI-1640 with 2% fetal calf serum supplemented with progesterone or medroxyprogesterone acetate (MPA) in a long-term culture system. Indirect immunofluorescent staining showed that fibronectin was uniformly distributed in the intracellular and extracellular regions of stromal cells treated with MPA for 14 days. The biosynthesis and secretion of this protein and the accumulation of cellular fibronectin mRNA were studied after various culture periods. Cells were pulse-labelled with [35S]methionine to determine the amount of newly synthesized fibronectin secreted into the culture medium. A monoclonal antibody (Mab) identified human fibronectin on SDS-polyacrylamide gel electrophoresis (SDS-PAGE), showing a predominant band (Mr 230-250 kDa) which migrated with authentic fibronectin run in parallel. In six endometrial specimens, the amount of radioactivity incorporated as [35S]fibronectin was increased by progestin. Maximal stimulation occurred after 6 days treatment with MPA. Culture beyond 16 days reduced the rate of synthesis and secretion to 40% of the maximum. The effect of progestin was dose dependent with 0.02, 0.2 and 1 microM progesterone, producing 2.0, 3.8 and 11-fold increases respectively, over the control. Medroxyprogesterone acetate was more effective than progesterone, the maximal response (10-fold increase) being achieved at 0.02 microM MPA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of serum complement (C3, C4) and immunoglobulin (IgG,IgM) levels with hormone replacement therapy in healthy post-menopausal women

BACKGROUND: Recently published data suggest that hormone replacement therapy (HRT) may increase cardiovascular risk during the early months of therapy. Activation of the immune system is known to be involved in several types of cardiovascular disease. In this cross-sectional study, serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving two different short-term HRT regimens, and in untreated women. METHODS: Serum C3, C4, IgM and IgG levels were assessed in 18 women receiving transdermal 17beta-estradiol (50 micro g/day) + continuous oral medroxyprogesterone acetate (MPA; 2.5 mg/day), in 56 women taking oral conjugated equine estrogen (CEE; 0.625 mg/day) + continuous MPA, and in 80 control women not receiving HRT. RESULTS: The mean serum C3 level was significantly higher in women using oral CEE + MPA than in women receiving transdermal 17beta-estradiol + MPA, and those not on HRT (P = 0.02 and P < 0.001 respectively). Furthermore, women taking oral CEE + MPA had significantly higher mean levels of C4 compared with untreated women (P < 0.01). IgG and IgM levels were similar among women either of the two HRT regimens and between women not on HRT. CONCLUSIONS: Oral HRT may be involved in the development of cardiovascular disease through inflammatory mechanisms, as suggested by increased serum levels of C3 and C4.     

A comparative study of two hormone replacement therapy regimens on safety and efficacy variables

Objective: To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women. Methods: In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups. Results: Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups. Conclusions: Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms     

Endometriosis: Serum-soluble CD23 in patients with endometriosis and the effect of treatment with danazol and leuprolide acetate depot injection

Activated B cells have recently been shown to produce solubleCD23 from their membranes. The serumsoluble CD23 concentrationin 21 patients with pelvic pain diagnosed as having endometriosisand confirmed by histology, and in 18 patients without pelvicpain, who had a normal pelvis during laparoscopic sterilization,was studied by chemiluminescent enzyme-linked immunosorbentassay. The endometriosis patients were randomized to 3 monthsof either danazol or leuprolide acetate injection. Serum wastaken before and after 3 months of therapy. The serum-solubleCD23 concentration was significantly elevated in patients withendometriosis when compared with the controls (P < 0.0001).There was no correlation between soluble CD23 concentrationsand the severity of endometriosis (r = 0.48, P > 0.05). Theserum concentration of soluble CD23 decreased significantlyon treatment with danazol but not leuprolide acetate (P <0.05). We conclude that the elevation of soluble CD23 in patientswith endometriosis suggests that there is activation of B cells,which respond to danazol but not leuprolide acetate injection.     

Plasma concentrations of medroxyprogesterone acetate, estradiol and estrone following oral administration of klimaxil®, trisequence® / provera® and divina®. A randomized, single-blind, triple cross-over bioavailability study in menopausal women

The absorption of estradiol and medroxyprogesterone acetate was investigated in a randomized single-blind, triple cross-over study, in 12 menopausal women, for four different HRT drugs (Klimaxil®, a combination tablet containing 17β-estradiol 2 mg and medroxyprogesterone acetate 5 mg; Divina®, a combination tablet containing 17β-estradiol valerate 2 mg and medroxyprogesterone acetate 10 mg; Trisequence®, a triphasic preparation containing 17β-estradiol 2 mg in the first phase; Provera®, a tablet containing medroxyprogesterone acetate 5 mg). Trisequence and Provera were ingested simultaneously. In conclusion, there was no statistically significant difference between the drugs with respect to the estradiol levels. The estrone concentration, however, differed between the different drugs. The serum concentration was higher after intake of tablets containing estradiol than after intake of tablets containing the valerate ester. There was a significant increase in the MPA levels between periods 1 and 3. Finally, Divina produced higher MPA concentrations than Klimaxil and the combination of Trisequence and Provera, although the mean AUC was not twice as high, as might have been expected.     

Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep residual endometriosis

Study objective: To compare the effect of HRT with transdermal estradiol and that of treatment with tibolone in post-menopausal women with residual endometriosis. Materials and Methods: 21 women with residual pelvic endometriosis after bilateral oophorectomy with or without hysterectomy were enrolled in the study and were randomized to HRT with transdermal estradiol 50 mg twice weekly (n=10) associated with cyclic medroxyprogesterone acetate 10 mg daily in women who preserved uterus, and to treatment with tibolone 2.5 mg administered orally once a day (n=11). The duration of both treatments was scheduled to last at least 12 months. Residual endometriosis was located in the bowel wall in four patients, in the rectovaginal septum in six and deeply in the retroperitoneal pelvic space in six. All women were symptomatic before oophorectomy. Results: All the women were followed for 12 months. No patient suspended therapy because of side effects. Four patients of the estradiol group experienced moderate pelvic pain during treatment compared with only one patient in the tibolone group. One patient in the estradiol group reported severe dyspareunia. Conclusion: Although our series is very small, it seems that tibolone may be a safe hormonal treatment for post-menopausal women with residual endometriosis.     

Effects of estrogen, raloxifene, and hormone replacement therapy on serum C-reactive protein and homocysteine levels

OBJECTIVES: To investigate the effects of conjugated equine estrogen (CEE), CEE plus medroxyprogesterone acetate (MPA), CEE plus Nomegestrol acetate (NA), and raloxifene on serum high sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in healthy postmenopausal women. MATERIALS: One hundred seven healthy postmenopausal women were recruited in a prospective, randomized, and placebo-controlled 6 months study. Of these, 18 were hysterectomized and received daily oral 0.625 mg CEE. Eighty nine non-hysterectomized women were randomly allocated to one of four groups: a group (22 patients) treated with CEE, 0.625 mg/daily plus MPA 2.5 mg/daily; a group (22 patients) treated with CEE, 0.625 mg/daily plus NA 5 mg/daily; a group (23 patients) treated with raloxifene hydrochloride, 60 mg once daily; and a placebo group (22 patients). Hcy and hs-CRP were measured at baseline and at 3 and 6 months. RESULTS: CEE (20%, P=0.03) and CEE+MPA (59%, P=0.006) increased serum hs-CRP levels significantly, whereas CEE+NA decreased serum hs-CRP by 25% (P=0.01). Raloxifene had no significant effect on serum hs-CRP levels during and after the treatment. In all active treatment groups serum Hcy levels decreased significantly compared to baseline and placebo. CONCLUSIONS: Conjugated equine estrogen, hormone replacement therapies, and raloxifene lower serum Hcy levels to a comparable extent in postmenopausal women. Hs-CRP, as a cardiovascular risk factor, is not influenced by raloxifene, whereas CEE and CEE plus MPA significantly increase hs-CRP levels. Treatment with CEE plus NA reduces serum hs-CRP levels.     

Maintained reduction of uterine leiomyoma following addition of hormonal replacement therapy to a monthly luteinizing hormone-releasing hormone agonist implant: a pilot study.

Ten pre-menopausal women with uterine leiomyoma were treated for 1 year with a monthly depot of luteinizing hormone-releasing hormone agonist (LHRA-a), goserelin, combined after the initial 3 months of treatment with conjugated oestrogens 0.3 mg (days 1-25) and medroxy-progesterone acetate 5 mg (days 16-25). Mean leiomyoma volume decreased by 49.3% during the first 3 months when goserelin alone was administered but did not change significantly during the 9 months of combination therapy. There were no significant changes in bone mass or high-density lipoprotein cholesterol during the study whereas hot flushes and menstrual blood loss were well controlled. These results indicate that ovarian suppression with a monthly depot of the LHRH-a, goserelin, combined after 3 months with low-dose hormonal replacement therapy reduced the size and the symptomatology of leiomyoma while preserving the bone mass.     

Intensive short-term chemotherapy in patients with advanced breast cancer

Summary Aiming at a high complete remission rate with an intensive induction regimen, 27 patients with advanced breast cancer were given three cycles of VAC chemotherapy consisting of vinde-sine 3 mg/m² i.v. on days 1 and 12, adriamycin 40 mg/m² i.v. on days 1 and 12, and cyclophosphamide 200 mg/m² p.o. on days 3–6 and 14–17 together with medroxyprogesterone acetate (MPA) 1,500 mg p.o. daily during the induction phase and 1,000 mg p.o. thereafter until relapse. These VAC double cycles were repeated twice with 3-weekly intervals for a total induction period of 15 weeks. In responders, including no change, the chemotherapy was discontinued thereafter, and the patients were observed until relapse with a maintenance therapy of MPA 1,000 mg p.o. daily.A complete remission (CR) was achieved in 8 (29.6%) and a partial remission (PR) in 13 (48.2%) of the 27 patients (CR + PR 77.8%). A no change (NC) status was found in 6 patients (22.2%). There were no nonresponders. The median duration of the CR was 20 (5–42) months with two patients still in CR at 33 and 36 months, of the PR 8.3 (4–13.5) months, and of the NC 6.7 (2–13) months. The treatment was tolerated without life-threatening toxicity or interval prolongation by all patients. No dose-limiting cardiac toxicity was observed in these patients regularly controlled by left ventricular ejection fraction (LVEF). The high response rate of this intensive induction regimen warrants further investigation. Complete remission was achieved only in patients without previous chemotherapy, with marked tumor regression after the first chemotherapy cycle and when there was no extensive bone involvement.Abbreviations ADR Adriamycin - CK Creatinine kinase - CK-MB Cardiac muscle specific isoenzymes - CMF Cyclophosphamide, methotrexate, 5-FU - CNS Central nervous system - CR Complete remission - CYC Cyclophosphamide - DFI Disease-free interval - ECG Electrocardiogram - LMF Chlorambucil, methotrexate, 5-FU - LVEF Left ventricular ejection fraction - MPA Medroxyprogesterone acetate - NC No change - PD Progressive disease - PR Partial remission - VAC Vincristine, adriamycin, cyclophosphamide - VEC Vincristine, epirubicin, cyclophosphamide - VDS Vindesine - WBC White blood cell count     

Medical and psychiatric symptoms in women with childhood sexual abuse.

Although there is increasing awareness of the short-term psychological and social adaptations to childhood sexual abuse, little is known about the long-term effects of such abuse, particularly its effect on subsequent medical utilization and the experience and reporting of physical symptoms. We re-analyzed data from a previous study of 100 women scheduled for diagnostic laparoscopy (50 for chronic pain, 50 for tubal ligation or infertility evaluation) who received structured, physician-administered psychiatric and sexual abuse interviews. Women were regrouped by severity of childhood sexual abuse, and we compared the groups with respect to lifetime psychiatric diagnoses and medically unexplained symptom patterns. Unadjusted odds ratios showed that risk for lifetime diagnoses of major depression, panic disorder, phobia, somatization disorder and drug abuse, and current diagnoses of major depression and somatoform pain disorder were significantly higher in the severely abused group compared with women with no abuse or less severe abuse. Logistic regression analysis demonstrated that number of somatization symptoms, lifetime panic disorder and drug dependence were predictive of a prior history of severe childhood sexual abuse. Psychiatric disorders and medical symptoms, particularly chronic pelvic pain, are common in women with histories of severe childhood sexual abuse. Clinicians should inquire about childhood sexual and physical abuse experiences in patients with multiple medical and psychiatric symptoms, particularly patients with chronic pelvic pain.