Genital chronic graft-versus-host disease: an unmet need that requires trained gynecologists.

OBJECTIVE: Menopause and chronic graft-versus-host disease (cGvHD) are the leading causes of morbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT). Genitalia are one of the target organs of cGvHD causing sexual dysfunction and local symptoms, which may impair women's quality of life. The aim of this study is to describe the prevalence and clinical characteristics of genital cGvHD. METHODS: A retrospective cross-sectional observational study was performed including 85 women with alloHSCT. All women were diagnosed and counseled by a trained gynecologist. Health-related quality of life was assessed by the Cervantes Short-Form Scale and sexual function was evaluated by the Female Sexual Function Index. RESULTS: Seventeen women (20%) included in the study were diagnosed with genital cGvHD. The main complaints were vulvovaginal dryness (42.2%) and dyspareunia (29.4%), the presence of erythema/erythematous plaques (52.9%) being the most frequent sign. Median time from transplant to diagnosis of genital cGvHD was 17 months among those with mild involvement, 25 months for moderate and 42 months for severe forms. Mortality was 29.4% in patients who developed cGvHD with genital involvement versus 8.8% among those without (p = 0.012). CONCLUSION: Early gynecological evaluation might allow to identify patients with mild forms of genital cGvHD, potentially enabling better management and improved outcomes.

Treating genitourinary syndrome of menopause in breast cancer survivors: main challenges and promising strategies.

Many breast cancer survivors (BCS) suffer the consequences of antineoplastic treatments that induce a hypoestrogenic state, leading to chronic climacteric symptoms such as genitourinary syndrome of menopause (GSM), arousing significant alteration in their quality of life. Non-hormonal therapies (NHT) are first-line treatments, safe but with mild efficacy. When facing moderate-severe GSM, the options for BCS are limited: local estrogen therapy, considered the 'gold standard' but with concerns about safety; vaginal androgens and prasterone, which seem to trigger an activation of estrogen and androgen receptors of the vaginal epithelium layers, without activating estrogen receptors on other tissues, being potentially safe but still without strong evidence in favor of BCS; vaginal lasers, which appear to improve vascularization of vaginal mucosa by stimulating the remodeling of the underlying connective tissue, but with contradictory results of efficacy in recent randomized clinical trials; and ospemifene, an oral selective estrogen receptor modulator presenting mild vaginal estrogenic potency and anti-estrogenic effect at the endometrial and breast level, but still not recommended for use in BCS in recent North American Menopause Society guidelines. There is a need for further studies evaluating objectively the efficacy and safety of these promising therapeutic options. On the other hand, sexuality must be seen as a multifactorial issue, where GSM is only part of the problem; evidence shows that sexual counseling improves the quality of life of BCS. Finally, there is a need to limit the underdiagnosis and undertreatment of GSM in BCS; the primary goal of physicians treating BCS regarding this issue has to be the provision of information of what to expect regarding genital and sexual symptoms to BCS and to counsel on early first-line treatments that may help prevent more severe GSM.

Safety of prasterone in breast cancer survivors treated with aromatase inhibitors: the VIBRA pilot study.

BACKGROUND: Due to safety concerns on estrogen-based treatments for genitourinary syndrome of menopause (GSM) in breast cancer survivors (BCS), new options are appearing, such as androgen-based treatments, which according to proprieties would not be transformed systemically to estrogens in patients receiving aromatase inhibitors (AIs). OBJECTIVE: The aim of this pilot study is to assess the security and efficacy of vaginal prasterone (dehydroepiandrostenedione [DHEA]) in BCS treated with AIs. METHODS: This open, prospective, pilot study included 10 BCS treated with AIs. All participants complained of severe GSM. DHEA was administrated as a vaginal ovule. Participants were instructed to use one ovule every night during the first month, and one ovule every two nights for the entire five remaining months. The patients were requested to attend seriated visits after the beginning of the prasterone treatment to evaluate symptoms, physical improvement and serum estradiol. RESULTS: Mean serum estradiol remained low from 3.4 pg/ml to 4.3 pg/ml (p = 0.9136) after 6 months of follow-up. The visual analog scale of dyspareunia improved from 8.5 to mean values after treatment of 0.4 (p = 0.0178). The Vaginal Health Index (VHI) scale and Female Sexual Function Index improved from 9.75 to 15.8 (p = 0.0277) and from an initial score of 11.2 to 20.6 (p = 0.0277), respectively. Vaginal pH changed from basal 8.1 to final 6.5 (p = 0.0330). CONCLUSION: Symptoms and physical examination regarding sexuality and vaginal health improved significantly, while serum estradiol remained at low levels. Prasterone seems a safe and effective option to treat GSM in BCS receiving AIs.

Controversies over the use of GnRH agonists for reduction of chemotherapy-induced gonadotoxicity.

The increase in cancer incidence in younger people and the significant improvement in long and permanent remission have brought concern about their reproductive future and quality of life. Up to two-thirds of adult female patients undergoing chemotherapy for malignancies eventually develop premature ovarian failure. This condition is related to many complaints including vasomotor symptoms, osteoporosis, increased risk of cardiovascular diseases, sexual dysfunction, and infertility. Therefore, protection against iatrogenic infertility and loss of endocrine ovarian function caused by chemotherapy is currently of high priority. Several options have been used for preserving ovarian function. Established methods include cryopreservation of embryos and/or ova, and ovarian transposition, while others such as ovarian tissue preservation are new, yet promising treatments for fertility preservation. The administration of gonadotropin releasing hormone (GnRH) agonistic analogs (GnRH-a) is still considered experimental. However, the recent evidence is strong to recommend the use of GnRH-a co-treatment during chemotherapy in young women with cancer to protect ovarian function, with promising results regarding fertility preservation. As the use of GnRH-a is non-invasive, highly available and without impact on cancer treatment outcomes, it should be offered to all young female cancer patients to preserve their ovarian function.

Effect of ospemifene on moderate or severe symptoms of vulvar and vaginal atrophy.

OBJECTIVES: To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach. METHODS: Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief. RESULTS: Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p < 0.00001), dyspareunia (p < 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p < 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching. CONCLUSIONS: For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA.

The clinical relevance of the effect of ospemifene on symptoms of vulvar and vaginal atrophy.

OBJECTIVES: To explore clinically relevant differences in severity of vulvar and vaginal atrophy (VVA) in postmenopausal women treated with ospemifene compared with placebo. METHODS: Analysis of two multicenter, randomized, double-blind, 12-week phase-III studies in postmenopausal women (40-80 years, with VVA, treated with ospemifene 60 mg/day or placebo (Study 310 and Study 821)). Severity of vaginal dryness and dyspareunia were evaluated using a four-point scoring system and clinically relevant differences between ospemifene and placebo were analyzed and are presented as improvement (reduction in ≥ 1 unit on four-point scoring system), substantial improvement (reduction in 2-3 units on four-point scoring system) and relief (severity score of mild/none after 12 weeks). RESULTS: In Study 310, significantly more women with a most bothersome symptom of dyspareunia had improvement (68.3% vs. 54.1%; p = 0.0255) or relief (57.5% vs. 41.8%; p = 0.0205) in the severity of dyspareunia from baseline to week 12 with ospemifene compared with placebo. For those with a most bothersome symptom of vaginal dryness, significantly more experienced improvement (74.6% vs. 57.7%; p = 0.0101), substantial improvement (42.4% vs. 26.9%; p = 0.0172) and relief (66.1% vs. 49.0%; p = 0.0140) of vaginal dryness from baseline to week 12 with ospemifene compared with placebo. Proportions of women with improvement/substantial improvement/relief of symptoms of vaginal dryness or dyspareunia were similar in Study 821. Clinically relevant differences were noticeable by week 4. CONCLUSIONS: Treatment with ospemifene was consistently associated with greater improvement, substantial improvement or relief in the severity of the most bothersome symptoms of vaginal dryness or dyspareunia compared with placebo.

Evidence-based assessment of the impact of the WHI on women's health.

Following the announcement of the first results of the Women's Health Initiative (WHI) to the media in 2002, prior to their scientific publication, the resulting panic headlines had an immediate and lasting negative effect on use of menopausal hormone replacement therapy (HRT) around the world. Rates of use dropped by 40-80%. Symptomatic women then sought multiple alternative therapies but the majority of these have no greater effect than the effect seen from placebo in well-conducted trials of HRT. Some of these therapies have risks. Although anecdotally most menopause practitioners after 2002 can attest to having to counsel large numbers of women with debilitating menopausal symptoms who were too frightened to consider HRT, it is difficult to document loss of health-related quality of life in large population studies as they were not conducted. Similarly, the positive or negative effects of the marked decline in HRT on long-term morbidities and mortality have yet to be fully assessed. Recent studies have shown an increase in postmenopausal fractures and in some, but not all, populations a small temporary decline in breast cancer. Cardiovascular outcomes may not be apparent for another decade. Short-term, randomized, placebo-controlled trials confirm that HRT is the only therapy that effectively improves health-related quality of life in symptomatic women through a reduction in vasomotor and urogenital symptoms, joint pains and insomnia, while improving sexuality. The results of the re-analyses of the WHI data and new data from other studies do not justify the continuing negative attitude to HRT in symptomatic women who start HRT near menopause.

Complications of hysteroscopic Essure(®) sterilisation: report on 4306 procedures performed in a single centre.

OBJECTIVE: To analyse the short-, medium- and long-term complications in women undergoing hysteroscopic tubal sterilisation with the Essure(®) device. DESIGN: Retrospective 7-year study. SETTING: Office hysteroscopic unit in a teaching hospital. SAMPLE: A total of 4306 women whoe underwent the Essure(®) sterilisation procedure from 2003 to 2010. METHODS: Data on the success of the procedure and complications arising from outpatient hysteroscopic sterilisation using the Essure(®) system were collected from consecutive women undergoing the procedure over a 7-year period. MAIN OUTCOME MEASURES: Placement rate, successful bilateral tubal occlusion, perioperative adverse events, early postoperative (during the first 3 months of follow-up) and late complications (after the initial 3 months of follow-up). RESULTS: A total of 4108 (96.8%) women completed the standard 3-month follow-up protocol. Only 534 (13%) women had undergone the procedure within the previous year. There were 115 (out of 4306; 2.7%) recorded complications, none of which resulted in the need for hospitalisation or discharge later than 2 hours after the procedure. Vasovagal syncope was the most frequently encountered adverse event, occurring in 85 (2.0%) of 4306 cases. In 19 cases, one device was expelled, with most expulsions (14 out of 19) being detected before or during the 3-month follow-up. CONCLUSIONS: Outpatient hysteroscopic sterilisation using the Essure(®) system is safe, with a low rate of complications.

The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III): prevalence of the metabolic syndrome in postmenopausal Latin American women.

BACKGROUND: Metabolic syndrome (METS) is a strong predictor of cardiovascular risk. Since the prevalence of METS increases after menopause, gynecological routine consultation offers an excellent screening opportunity. OBJECTIVES: To assess the prevalence of METS in Latin American postmenopausal women and factors modifying its risk; as well as to assess the role of simple routine care measurements in the diagnosis of the METS. METHODS: A total of 3965 postmenopausal women, aged 45-64 years, seeking health care at 12 gynecological centers in major Latin American cities were included in this cross-sectional study. The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) guidelines were applied to assess METS. This was present if three or more of the following conditions were present: waist circumference > or = 88 cm; blood pressure > or = 130/85 mmHg; fasting plasma triglycerides > or = 150 mg/dl; high density lipoprotein (HDL) cholesterol < 50 mg/dl; glucose > or = 110 mg/dl or subjects were receiving treatment for their condition. RESULTS: The prevalences of having at least two, three, four or five components were 62.5, 35.1, 13.5 and 3.2%, respectively. The prevalence increased from 28.1% in those aged 40-44 years to 42.9% in those aged 60-64 years. The risk of METS detection (multivariate analysis) increased with age (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.03-1.43), time elapsed since menopause (OR 1.18, 95% CI 1.00-1.38), smoking cigarettes (OR 1.40, 95% CI 1.19-1.65), obesity (OR 13.01, 95% CI 10.93-15.49) and hypertension (OR 9.30, 95% CI 7.91-10.94). In contrast, hormone therapy reduces this risk (OR 0.59, 95% CI 0.51-0.70). CONCLUSION: There is a high prevalence of the metabolic syndrome in postmenopausal Latin American women seeking gynecologic health care. Age, years since menopause, obesity and hypertension are strong predictors of this condition.

Effect of a compound containing isoflavones, primrose oil and vitamin E in two different doses on climacteric symptoms.

The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial. A total of 1,080 postmenopausal women, with climacteric symptoms, were allocated into one of two treatment groups to receive one (Group 1; n = 562) or two IOVE capsules (Group 2; n = 518) per day. The Blatt - Kupperman scale and safety parameters including weight, body mass index, blood pressure and adverse effects were assessed at the first visit before initiating the treatment, and 3 - 6 months thereafter. In addition, cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride levels were measured at baseline and at the 6th month visit. Finally, at the end of follow-up, the patient's satisfaction was assessed. No differences between groups at the beginning of the study and during the follow-up were observed. A significant reduction in Blatt - Kupperman scores were observed in the two groups. In addition, the reduction of the symptoms was more intense in the first 3 months. Increasing doses of IOVE add no beneficial effects since both studied doses were equally effective in the reduction of climacteric complaints.

Management of menopause.

Menopause signifies the permanent cessation of ovarian function and the end of a woman's reproductive potential. A universal experience in women's aging, it is the culmination of many years of reproductive aging; a process that unfolds as a continuum from birth through ovarian senescence to the menopausal transition and the postmenopause. The menopausal transition is known to play a major role in the etiology of many symptoms common in middle age and may contribute to chronic conditions and disorders of aging such as osteoporosis, cardiovascular diseases and cancer. Recent data suggest an unacceptable increase in morbidity in a number of women using hormone therapy (HT). Thus, during the past few years, many women and doctors have revised their opinions on HT for menopause-related symptoms, and a substantial number of individuals have discontinued its use because of concerns about side-effects, owing to this, numerous alternatives to HT are promoted, and researches have pointed out the interest in a group of molecules such as selective estrogen receptor modulators (SERMs) (i.e. raloxifene) and phytoestrogens. Further studies may open a new panorama in patient-specific management of postmenopausal health. Careful assessment of the midlife woman allows for individualized risk-benefit analysis with the formulation of a specific health management plan.

Raloxifene inhibits cholesterol aortic content but not atherosclerotic plaque size in oophorectomised cholesterol-fed rabbits.

Raloxifene, a selective oestrogen receptor modulator, is effective in the treatment of osteoporosis without stimulating the breast and the endometrium. Although it is associated with a decrease of cardiovascular risk markers the effect of these changes on atherogenesis, is not clear. In this study, we aimed to investigate the effect of raloxifene on aorta atherogenesis. A total of 32 cholesterol-fed New Zealand white rabbits were studied for 4 months. Twenty-four rabbits underwent bilateral ovariectomy; of these eight received raloxifene (group OR), eight received oestradiol valerate (group OE) and eight received placebo after sterilisation (group OP). Finally, another eight were sham-operated (non-ovariectomised) and received placebo with a hypercholesterolaemic diet (group SP). After the diet, total levels of cholesterol increased in group SP from 111.25 +/- 34.8 mg/dl to 1112.25 +/- 364.2, in group OP from 122.62 +/- 27.7 mg/dl to 1367.37 +/- 348.4, in group OE from 65.25 +/- 17.01 to 1710.5 +/- 356.2 and in group OR from 108.88 +/- 15.54 mg/dl to 1407.86 +/- 397.7 (no significant differences). At 4 months, in both treated and untreated rabbits, the cholesterol-rich diet caused atherosclerotic lesions affecting 24.51 +/- 16.1% for group SP, 30.47 +/- 12.2% for group OP, 30.31 +/- 18.07% for group OR and 17.91 +/- 10.19 for group OE (P<0.05) of the aortic surface, respectively. Aortic cholesterol expressed as mg of cholesterol/mg aortic weight was found to decrease in raloxifene-treated rabbits: 3.82 +/- 2.14 mg col/aortic mg versus 8.55 +/- 4.63 (group OP) and 11.97 +/- 11.33 (group SP). P<0.001. Raloxifene reduced aortic cholesterol content but not the atherosclerotic plaque extension in cholesterol-fed ovariectomised rabbits.

Alendronate daily, weekly in conventional tablets and weekly in enteric tablets: preliminary study on the effects in bone turnover markers and incidence of side effects.

Bisphosphonates are now in the vanguard of osteoporosis treatment. Frequently, gastro-oesophageal symptoms are associated with these drugs. The objective of this study was to compare side effects and bone turnover markers in postmenopausal women who had received alendronate daily or weekly in tablets with or without enteric coating. We conducted a randomised, double-blind, 3-month trial. The trial involved 75 volunteers, aged 45-58 with moderate to severe osteopenia (T-score lower than -2 SD) assessed by quantitative ultrasound. Women were assigned randomly to receive: (a) alendronate 10mg/day: (b) alendronate 70 mg once a week: or (c) enteric alendronate 70 mg per week. We recorded side effects, C-telopeptide, osteocalcin and urine hydroxyproline at the start of the study and at 3 months. After 3 months, pyrosis (heartburn) was noted by seven women in group A (28%), three in group B (12%) and two in group C (8%); nausea: by one woman in group B; and headache by one patient in each group. C-telopeptide (A: 40.7%; B: 34.1% and C: 38.5%); hydroxyproline (A: 31.1%;B: 25.3% and C: 31.5%) and osteocalcin (A: 27.0%; B: 25.4% and C: 25.1%) decreased similarly in the three groups. Weekly intake of alendronate, whether conventional or enteric-coated; is associated with less heartburn and nausea. Enteric alendronate has a similar action to the conventional tablets on biochemical markers.

Effects of transdermal estrogens on endothelial function in postmenopausal women with coronary disease.

OBJECTIVE: Oral estrogens improve endothelial function, and for this reason may be considered cardioprotective; however, in women with coronary heart disease there may also be an increase in the risk of thrombosis. Although transdermal estrogen administration may decrease this adverse effect, there are few data on endothelial function in women with coronary heart disease treated using such therapy. This study aimed to report the endothelial response in postmenopausal women with coronary heart disease treated with transdermal estrogen. MATERIALS AND METHODS: This was a double-blind, prospective, randomized study. Eighteen patients with a history of acute coronary syndrome and nine healthy women were studied over 4 weeks. Coronary patients were assigned at random to receive a patch containing either 50 microg estradiol or placebo on a weekly basis. Endothelial function was assessed by flow-mediated vasodilatation of the brachial artery. Baseline blood flow (brachial artery diameter) was measured after 30 min rest and following ischemia, prior to treatment and after 4 weeks. RESULTS: Flow-mediated vasodilatation in normal patients was 17.8%, whereas in women with coronary disease it was 1.2% (p = 0.0001). Arterial diameter for the resting period in coronary disease subjects increased from 4.22 +/- 0.59 to 4.41 +/- 0.56 mm (p < 0.004) after 4 weeks of estrogen therapy, whereas, in women receiving placebo, it did not change. Flow-mediated vasodilatation in the estrogen group was 3.4% and in the placebo group was 0.5% (p = 0.05). CONCLUSIONS: Transdermal estrogen may improve endothelial function in women with coronary heart disease.

Effects of estradiol, cyproterone acetate, tibolone and raloxifene on uterus and aorta atherosclerosis in oophorectomized cholesterol-fed rabbits.

BACKGROUND: Different hormonal replacement regimens are used for treating climacteric complaints; however, not all of them have the same clinical profile. Cardiovascular disease (CVD) is a major health problem and tibolone, raloxifene, estradiol (alone or with cyproterone acetate) have been added to cholesterol-fed rabbits to study atherosclerosis. METHODS: A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. Forty rabbits underwent bilateral ovariectomy and the other eight were sham operated (group S). The ovariectomized rabbits were allocated to five groups of eight animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day), estradiol valerate plus cyproterone acetate (EC, 3+0.5 mg/day, respectively), and no treatment for the control group (C). The sham group received no treatment too. RESULTS: After 4 months the percentage of the extent of atherosclerosis in the aorta was 30.4% in C group, 24.5% in S group, 10.2% in T group, 30.3% in R group, 17.9% in E group and 28.1% in EC group (P<0.05 T vs. C, R, EC). The aortic cholesterol content compared with aortic weight was 8.55 microg/mg in C group, 11.97 microg/mg in S group, 1.86 microg/mg in T group, 3.82 microg/mg in R group, 2.86 microg/mg in E group and 5.24 microg/mg in EC group (P<0.05 T vs. EC, C, S; R vs. C, S; E vs. C, S). Uterine weights in grams were: 1.89 (C group), 2.24 (S), 7.38 (T), 1.94 (R), 9.92 (E), and 5.94 (EC); P<0.05 (C, S, R, vs. T, E, EC; T vs. E; EC vs. T, E). CONCLUSION: Our study showed a decrease in the extent of aortic atherosclerosis in oophorectomized cholesterol-fed rabbits treated with tibolone or estradiol, and a decrease in aortic cholesterol content in rabbits treated with tibolone, raloxifene and estradiol. However, rabbits treated with tibolone showed an increased uterine weight, which is contrary to that observed in humans.

Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives.

OBJECTIVE: To evaluate whether decreasing doses of ethinyl estradiol affect bone loss related to hypothalamic amenorrhea. STUDY DESIGN: Sixty-four women with hypothalamic oligoamenorrhea were allocated to two therapy groups: group A (n = 24) received an OC containing 0.030 mg of ethinyl estradiol (EE) and 0.15 mg of desogestrel. Group B (n = 22) received an OC containing 0.020 mg of EE and 0.15 mg of desogestrel. Eighteen women who did not wish to use hormonal therapy constituted the control group (C). Calcium, phosphate and osteocalcin were measured basally and at 6 and 12 months of follow-up. Bone mineral density at the lumbar spine was determined before initiation of the study and at 12 months by dual energy X-ray absorptiometry. RESULTS: Serum calcium, phosphate and osteocalcin were significantly reduced by both active treatment regimens, whereas no differences were observed in the control group. Bone mineral density at 12 months showed an increase in both therapy groups (A, 2.4%; B, 2.5%), while group C showed a significant decrease (1.2%, P < .05). CONCLUSION: Both doses of EE were equally effective in preventing bone loss related to hypoestrogenism in hypothalamic oligoamenorrheic subjects.

Use of gonadotropin-releasing hormone analog with tibolone to prevent cyclic attacks of acute intermittent porphyria.

A 25-year-old woman with a 10-year history of recurrent attacks of acute abdominal pain just before menstrual periods had acute intermittent porphyria (AIP) diagnosed when she was 23.5 years old. Many acute attacks required hospitalization. Suppression of the menstrual cycle with a gonadotropin-releasing hormone analog (GnRHa; triptorelin) and tibolone administration as add-back therapy resulted in absence of acute porphyric attacks. The patient had no acute attacks over a 1-year follow-up period. This case suggests that long-term GnRHa therapy with tibolone add-back may be a therapeutic option for patients with AIP.

Do women using hormone replacement treatment have less pre-existing cardiovascular risk.

BACKGROUND: Several studies have suggested that women who choose to use hormone replacement therapy (HRT) already, before starting this therapy, have a better cardiovascular risk profile than those who do not use it. Some of these studies contain factors of confusion and biases, such as HRT users' greater educational achievement or physical activity, which could have led to wrong conclusions. AIM: To study a cohort, without confounding factors in order to analyse whether the cardiovascular risk profile is different in women who choose to use HRT. MATERIAL AND METHODS: Coronary risk factors of 387 women between 45 and 64 were studied. This study was carried out at the Unit for the Preventive Medical Examination of the South Metropolitan Health Service in Santiago (Chile) during the annual check-up. The first evaluation was in 1991-1992; with a second evaluation 5 years later. Of all the women, 174 (45%) never received hormones (Group A), 124 (32%) were HRT users at the time (Group B), and 89 (23%) were former-users (Group C). RESULTS: No differences were found between the three groups for age, body mass index (BMI), educational background, alcohol consumption, smoking or physical activity. Blood pressure was similar in the three groups. No significant differences were found in total cholesterol (A, 221.7+/-42.2; B, 228.2+/-47.0; and C, 227.3+/-44.9 mg/dl); high density lipoprotein (HDL, A, 53.5+/-13.2; B, 51.8+/-12.8; and C, 54.0+/-12.4 mg/dl); low density lipoprotein (LDL, A, 141.7+/-38.9; B, 148.5+/-43.1 and C, 148.3+/-43.8 mg/dl); triglycerides (A, 134.5+/-67.9; B, 141.0+/-66.1; and C, 127.3+/-68.5 mg/dl) and glucose plasma levels (A, 90.5+/-32.2; B, 87.7+/-15.3; and C, 85.0+/-8.8 mg/dl). CONCLUSIONS: Our results suggest that women who choose to use HRT have a cardiovascular risk profile, before starting the therapy, similar to those who do not use it.

Mycosis fungoides and pregnancy.

Mycosis fungoides is a cutaneous T-cell lymphoma, a subgroup of non-Hodgkin's lymphomas, characterized by skin infiltration and occasionally systemic involvement. The association of pregnancy and mycosis fungoides has not been described previously. A case of mycosis fungoides, stage IVb, in a pregnant woman is reported. Prior to pregnancy, the patient received adriamycin, cyclophosphamide, vincristine prednisolone (CHOP) and bleomycin and total body irradiation. Around the concepcional period she presented a cutaneous relapse palliated with photon radiotherapy. No obstetrics complications were observed during gestation. At 39 week's gestation a cesarean section was performed and a healthy 2900 g boy was delivered. Mycosis fungoides did not worsen during pregnancy and postpartum period. In conclusion mycosis fungoides did not adversely affect pregnancy outcome and gestation did not worsen the malignancy course. This case report may be valuable in managing patients with mycosis fungoides who are currently pregnant or are contemplating pregnancy.