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.

Peer review? No thanks!

The peer review process is an inalienable necessity in the modern scientific world. Published manuscripts are founded on feedback, a process in which reviewers evaluate the scientific values of the submitted paper and provide comments and criticisms. The aim of this process is to assist authors by improving their papers, to promote good science. The peer-review process can be represented as a hurdle race with the ultimate prize of innovative accurate scientific knowledge being published. In this process, we have on the one side the authors and originators of ideas and on the other editors and reviewers. In the process of publishing a scientific article, it is important to respect the time and efforts of both actors.

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.

Pre-induction cervical ripening with different initial doses of intravaginal misoprostol: time to delivery and peri-natal outcomes.

From 2016 to 2018, a total of 300 pregnant women underwent induction of labour. Those women were allocated in two groups according to the initial dose of misoprostol. Group I (150 women) received intravaginally 50 µg misoprostol followed by 25 µg every four hours, up to a maximum of four doses whereas in group II (150 women) the initial dose was 25 µg intravaginal followed by the same dose every four hours up to a maximum of four doses. Women with previous uterine scar, abnormal foetal heart rate, severe foetal malformation, foetal growth restriction or multiple pregnancy were excluded. The aim of study was to compare the effectiveness (hours until delivery) and perinatal outcomes of both schemes of cervical ripening. Initial doses of 50 µg of misoprostol reduced the time until delivery (17.65 ± 8.2 hours vs. 20.85 ± 9.3 hours; p=.007) and the need of oxytocin (34.6% vs. 46.67%; p=.046), compared to the use of 25 µg misoprostol in all doses. No differences were observed regarding perinatal outcomes.In conclusion, starting with 50 µg of misoprostol in the first dose reduced time to vaginal delivery and decreased the use of oxytocin without worse perinatal outcomes.Impact StatementWhat is already known on this subject? The rate of labour induction is increasing. Mechanical and medical methods try to establish the active phase of labour as quickly and safely as possible. For this reason, there are numerous studies assessing different protocols, dosages and indications.What do the results of this study add? Despite the numerous studies, due to ethical restrictions, it is difficult to carry out prospective studies. For this reason, studies like this help to establish the most appropriate dose of misoprostol in two of the most common indications for induction of labour. We demonstrated that increasing initial doses up to 50 mg of misoprostol are safer and more effective.What are the implications of these findings for clinical practice and/or further research? This study could be useful for future prospective and randomised studies as well for including these data in a meta-analysis. In addition, these results may update the clinical protocols and reduce hospital stay without worse perinatal outcomes.

Weight gain in menopause: systematic review of adverse events in women treated with black cohosh.

Weight gain is a frequent problem in perimenopausal and postmenopausal women. Cimicifuga racemosa (CR) is a popular treatment option for menopausal symptoms. The aim of this review was to investigate whether there is scientific evidence that CR causes weight gain. We searched our database for medically confirmed, spontaneous adverse events regarding weight gain, literature for case reports and randomized controlled trials. Thirty cases in total were spontaneously reported in 15 years. The causality was not considered certain/likely in any of the cases. A nurse (consumer) assessed the causality as possible. Only one case was published in the literature. However, no change in body fat composition was reported, and the causality seems unlikely. Of the 31 identified studies, 17 were double-blind placebo-controlled, five were double-blind reference-controlled and nine were open reference-controlled. In total, 1839 women were treated with CR for up to 12 months. Two studies reported weight gain as an adverse event; however, no significant differences in weight changes were observed between the groups. One case of weight gain (about 2 kg) was reported, but the authors did not specify in which treatment group. In conclusion, this study provides no scientific evidence that the use of Cimicifuga racemosa causes weight gain in menopausal women.

Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence.

A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of -0.694 in favor of iCR (p < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort (Hypericum perforatum [HP]) were given (-1.020 and -0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit-risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.

Gender differences in the prevalence of vitamin D deficiency in a southern Latin American country: a pilot study.

Aim: This study aimed to study the prevalence of vitamin D deficiency, assessing the influence of sex, age, and season of the year.Methods: A cross-sectional study was conducted with 1329 healthy subjects (668 women and 661 men) aged 18-89 years in Santiago, Chile. Age (years), body mass index, medical history, working status, sex, and date of blood sample were collected.Results: Men were slightly older than women (53.1 ± 18.2 vs. 50.0 ± 15.6 years; p < 0.01) and a higher percentage worked outside the home (73.1% vs. 51.9%, p < 0.001). The mean serum concentration of 25-hydroxyvitamin D (25(OH)-D) was 23.3 ± 9.3 ng/ml in women and 20.9 ± 9.5 ng/ml in men (p < 0.001). The levels of 25(OH)-D by season were 26.7 ± 9.0, 23.6 ± 9.7, 19.4 ± 8.5, and 19.1 ± 9.5 ng/ml (for summer, fall, winter, and spring, respectively; p < 0.05). The prevalence of vitamin D deficiency increases with age, rising from 36.5% under 40 years to 48.0% over 60 years (p < 0.004). Male sex, winter and spring, and age showed negative correlation with levels of 25(OH)-D (p < 0.05). Multivariate linear regression showed a final model that incorporates: age (coefficient: -0.06; 95% confidence interval [CI]: -0.09 to -0.03; p < 0.001), male sex (coefficient: -2.00; 95% CI: -2.96 to -1.05; p < 0.001), summer (coefficient: 7.30; 95% CI: 6.17 to 8.43; p < 0.001), and fall (coefficient: 4.27; 95% CI: 3.04 to 5.50; p < 0.001).Conclusions: Vitamin D deficiency is more prevalent in men than in women, in the elderly, and during the winter and spring seasons.

Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss.

Objective: This study aimed to compare the efficacy and safety of ossein-hydroxyapatite complex (OHC) versus calcium carbonate (CC) for preventing bone loss during perimenopause in current clinical practice.Methods: The prospective, comparative, non-randomized, open-label study included 851 perimenopausal women with basal bone mineral density (BMD) T-score ≥-2 standard deviations (SDs). Participants received either OHC (712 mg calcium/day) or CC (1000 mg calcium/day) over 3 years. BMD was evaluated by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4) at baseline and after 18 and 36 months of follow-up. Adverse drug reactions (ADRs) were also recorded.Results: In women receiving OHC, BMD at the L2-L4 site remained stable over the 3-year follow-up period (mean [SD] change 0.00 [0.11] g/cm2). BMD in the CC arm decreased -3.1% (mean [SD] - 0.03 [0.11] g/cm2). Between-group differences were statistically significant (p < 0.001) and favored OHC. ADRs were more frequent in the CC group (7.7% vs. 2.7% in the OHC group; p = 0.001), affecting primarily the gastrointestinal system.Conclusion: OHC showed greater efficacy and tolerability than CC for bone loss prevention in perimenopausal women in real-world practice. As the daily dose of calcium was higher in the CC group, the differences might be linked to the ossein compound in OHC.

Vulvar and vaginal atrophy as viewed by the Spanish REVIVE participants: symptoms, management and treatment perceptions.

OBJECTIVES: To gain a deeper comprehension of current vulvovaginal atrophy (VVA) knowledge among Spanish postmenopausal women. METHODS: An online survey (REVIVE) was conducted in four European countries with an overall sample of 768 participants included in Spain. Perceptions, experiences and needs of Spanish postmenopausal women in terms of sexual and vaginal health were reported. RESULTS: Vaginal dryness was the most common VVA symptom in Spain (81%). The severity of symptoms reported by postmenopausal women tended to be similar or worse than at onset, especially in the most troublesome symptom, dyspareunia (80%). VVA symptoms significantly impact on Spanish participants' ability to achieve sexual enjoyment (75%), relationship with partner (67%) and sexual spontaneity (66%). Although 71% of participants with partners (83%) were sexually active, their sex drive was reduced by one-third as a consequence of VVA. Despite the fact that women expected doctors to start asking them about menopausal symptoms, this rarely occurred. Treatments were administered mainly vaginally without prescription (62% were using over-the-counter products at the time). Postmenopausal women who had discussed their symptoms with physicians were twice as likely to be treated (66% vs. 33%) than those who had not. Low compliance with treatment was justified by Spanish participants with not bothersome enough symptoms (22%), relief (21%), inability to reverse vaginal changes (15%) and treatment price (13%). Almost half of the participants with a current local estrogen prescription showed satisfaction. The acknowledged main limitation for all treatments was the inability to restore the natural conditions of the vagina. The price of over-the-counter products was also reported as an important concern in Spanish postmenopausal women. CONCLUSION: VVA remains underdiagnosed and undertreated in Spain, despite its high frequency and significant impact on quality of life. Since patient satisfaction with available treatments remains compromised, an effective discussion of symptoms and therapies with doctors would improve its management.

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.

Cardiovascular risk in climacteric women: focus on diet.

A literature search was made using PubMed. The proportion of postmenopausal women has been continually increasing because of enhanced life expectancy. However, accompanying this trend, there is an observed increase in mortality due to cardiovascular disease (CVD). All over the world, obesity rates are increasing and this fact is associated with expanded rates of hypertension, dyslipidemia, and diabetes. Many of these well-known risk factors for CVD can be modified by lifestyle changes. For this reason, nutritional strategies to prevent CVD in this population should be a primary objective for health-care providers. Any attempt at lifestyle modification should include behavioral changes and the implementation of healthy diets and physical activity. The Mediterranean diet is comparable with other interventions such as aspirin, statins, physical activity, and even antihypertensives in terms of reducing the risk of CVD morbidity, mortality and events. The aim of this review is to analyze the effect of dietary advice on postmenopausal women's health.

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.

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

BACKGROUND AND OBJECTIVE: The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. MATERIAL AND METHODS: A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. RESULTS: Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. CONCLUSION: The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

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.

Essure® and chronic pelvic pain: a population-based cohort.

The aim of this study was to assess the incidence of chronic pelvic pain in women after placement of Essure® microinserts. This was a case series study at the hysteroscopy unit in a teaching hospital. We included 4,274 patients undergoing permanent sterilisation with Essure® microinserts from January 2005 to December 2011. Essure devices were removed in all patients reporting pelvic pain after insertion. All data were collected from the hysteroscopy unit database with later review of medical records in cases of chronic pelvic pain and a telephone survey after microinsert removal. Main outcome measures were: grade of procedure difficulty perceived by the surgeon; tolerance described by the patient after placement; the need for analgesics during or immediately after the procedure; side-effects; average time between device placement and the onset of symptoms; time between device placement and removal; technique for device removal and any symptoms thereafter. A total of seven women (0.16%) presented with chronic pelvic pain requiring microinsert removal, with four classifying the pain perceived during the procedure as medium-high. Six patients did not require analgesics after the procedure and a vasovagal syndrome requiring intravenous analgesia and monitoring occurred in only one case. Six women reported pain immediately after the procedure, with a mean time between placement and removal of 29.4 months. In all cases, the symptoms disappeared after Essure removal. We conclude that the development of chronic pelvic pain is very uncommon after placement of Essure microinserts. Removal of these devices usually improves the pain.

Effects of a 12-month multi-component exercise program on the body composition of postmenopausal women.

OBJECTIVE: The aims of this study were to identify the effects of a 12-month exercise program on the body composition of postmenopausal women and to examine the interaction of menopause characteristics (nature and time since menopause, hormone therapy) with exercise. METHODS: A total of 158 postmenopausal Caucasian women were analyzed in this study (70 in the control and 88 in the exercise group). This subset is part of the 'Shape up during menopause' which is a program that aims to develop exercise and health promotion in postmenopausal women. Exercise and control groups were tested before and at the end of the program. Data related to menopause were obtained through medical history. Measurements of fat mass, visceral fat area, skeletal muscle mass, fat-free mass, soft lean mass, and basal metabolic rate were assessed by octopolar bioimpedance. RESULTS: Alongside basal metabolic rate, all the anthropometric and body composition variables were influenced by the exercise program. The major differences between groups were found in skeletal muscle mass, total soft lean mass, fat-free mass, and skeletal muscle mass index (effect sizes ranged from 0.89 to 6.64). There were no interactive effects found between exercise and menopause characteristics. CONCLUSIONS: There were positive changes in all measured variables and no significant interactive effects with menopause characteristics; therefore, our data suggest that exercise alone promoted improvements in the body composition of postmenopausal women.

Long-term effect of hormone therapy on bone in early menopause: vertebral fractures after 20 years.

OBJECTIVE: The role of menopausal hormone therapy (HT) on vertebral fracture prevention after treatment discontinuation is controversial. The aim of this study was to assess the incidence of vertebral fracture in a group of women who received HT in early menopause compared with another group who did not receive such treatment after 20 years of follow-up. SUBJECTS AND METHODS: In 1990, we included 177 patients aged 43-57 years old (mean 49.1 ± 3.9 years) in a prospective study to evaluate the effect of different HT regimens on bone metabolism and mineral density. After 20-21 years, a total of 49 patients from the initial study were retrieved. These patients were divided into two groups: the first group included women who had taken HT, and those who constituted the control groups and had not taken HT formed the second group. Clinical and demographic data were analyzed and vertebral fracture was assessed by radiology using the Genant semiquantitative scale. RESULTS: Of the 49 patients enrolled, 32 (65.3%) received HT for an average of 5.5 (± 2.96) years while the 17 (34.7%) remaining belonged to the control group without treatment. A higher rate of vertebral fracture was observed in the group receiving HT (p = 0.03). Depending on the degree of fracture (Genant semiquantitative method), subsequent analysis by subgroups corroborated the higher rate in the group receiving HT in all cases (p < 0.05). Multivariate analysis ruled out the effect of the clinical and demographic variables (current age, age at menopause, body mass index, type of menopause and drugs for the treatment of osteoporosis) in the final result. CONCLUSION: In spite of the fact that this study does not have a large enough sample, our data suggest that HT used in the early years of menopause does not present a long-term protective effect on vertebral fracture after discontinuing treatment.