Menopause Hormone Therapy in the Management of Postmenopausal Osteoporosis.

ABSTRACT: This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks.

Menopausal hormone therapy and breast cancer risk.

This narrative review analyses the customization of Menopause Hormone Therapy in the context of breast cancer risk in women with premature ovarian insufficiency (POI) and with menopause at a normal age. Women with Idiopathic POI, FMR-1 premutation or Turner syndrome, if left untreated, may have lower breast cancer risk compared to the healthy age-matched female population. These women should be treated with MHT until the age of 50, as the risk of breast cancer is equal to that of normally menstruating women. Carriers of BRCA 1 & 2 mutation after risk-reducing bilateral salpingo-oophorectomy (RRSO), without a personal history of cancer, have an increased breast cancer risk, but may probably be treated with MHT till the age of 50. POI resulting from endometriosis or cancer related treatment is discussed in a separate paper in this issue. In peri- and postmenopausal women with menopausal symptoms and/or risk factors for osteoporosis in need of MHT, the individual breast cancer risk can be evaluated using internet-based calculators. In most women the 5-year-breast cancer risk is low (<3%) and MHT is a safe option. MHT should be prescribed with caution in women who have an intermediate risk (3-6%) and should not be prescribed in those who have a high risk of breast cancer (>6%). Oestrogen-only MHT and oestrogen-progestogen MHT containing micronized progesterone or dydrogesterone are associated with lower breast cancer risk compared to other combined MHT regimens.

Assessment of environmental knowledge and needs among assisted reproductive technology professionals.

PURPOSE: Exposure to environmental contaminants is to be taken into account in preventive healthcare in general and particularly in the field of reproduction according to the increasing amount of evidence data being published. The aim of this study is to evaluate the practices and interest in and basic knowledge of environmental health, by the professionals of the ART process: doctor, embryologist, and nurses. METHODS: Survey among 12 Belgian assisted reproductive technology (ART) centers. RESULTS: The response rate was 67%: 43.5% of the ART professionals do bring up the topic of environmental contaminants with their patients, without significant differences among types of professionals. Ninety percent of respondents believe that it would be useful, and 63% mention their lack of knowledge and the absence of solutions (20.5%) to explain their inaction. Lack of knowledge is much greater for nurses respectively (85%) compared with doctors (52%) and biologists (54%). The most popular means toward improving their knowledge is scientific seminars (69%). The questionnaire to evaluate the health professional knowledge gives 56% of adequate replies. The topic concerning eating habits obtains a very bad score of knowledge. When looking at exposure to occupational risks, 75% of the answers were correct. CONCLUSIONS: The place of ART before conception makes it an ideal entry point for the prevention of environmental hazards. This study corroborates the previous observations which underline the importance to reinforce the concepts of environmental health in the initial and continuous training of health professionals.

Suspension of ulipristal acetate for uterine fibroids during ongoing EMA's review of liver injury risk: Unfortunate timing during the Covid-19 pandemic!

OBJECTIVE: EMA decided that with ulipristal acetate (UPA) treatment for uterine fibroids, should be discontinued due to the associated risk of hepatic failure, We analyzed whether the risk of recurrent symptoms due to fibroids may lead to an increased risk of Covid -19 infection and death, that would exceed the former risk of hepatic failure and transplantation. STUDY DESIGN, SIZE, DURATION: We used a Markov model to generate probabilities. PARTICIPANTS/MATERIALS, SETTING, METHODS: There are currently about 36,250 treated patients in Europe. We estimated bleeding probabilities, while using or discontinuing UPA, which may induce a need of medical or surgical management in symptomatic patients, and increase the risk of acquiring a Covid-19 infection, and die from it. We also estimated the risk of suffering a hepatic failure and hepatic transplantation. MAIN RESULTS AND THE ROLE OF CHANCE: Based on our assumptions, ceasing UPA during a Covid 19 pandemic may be associated with a fatality ratio between 4 and 18, due to the Pandemic, whereas pursuing UPA would be associated with a fatality rate due to the pandemic between 1-2, and an added fatality rate due to hepatic impairment of 1. The added risk of stopping UPA may range between 2 and 15 additional deaths. Our calculations suggest that the decision to stop UPA in the middle of the Covid- 19 pandemic may be untimely, since it may result in an increased risk of Covid-19 infection, due to the recurrence of symptoms and the need for medical and surgical treatment. WIDER IMPLICATIONS OF THE FINDINGS: A decision, like the one EMA took need to be taken in a wider health context of a population, than simply analyzing its role as regulating agent for medications.

Are we equal in adversity? Does Covid-19 affect women and men differently?

BACKGROUND & OBJECTIVES: This article examines whether women are less prone than men to Covid-19 infections and their complications. DATA SOURCES: We reviewed available databases and searched systematically for publications. To be taken into account, data had to be broken down by gender. There was no study evaluation nor quantification synthesis, due to the large heterogeneity of the studies. Nineteen databases were selected. 73 publications were considered and 33 were selected, to which 12 more were added. RESULTS: Globally, the proportion of men and women who tested positive is comparable. However, men are about 60 % more likely to be severely ill or to die from the complications of Covid-19 than are women. LIMITATIONS: The study was hampered by a large heterogeneity in testing and reporting of the data. CONCLUSIONS: Although in the pandemic men die more frequently than women from Covid-19, it is not clear whether this is due to biological differences between men and women, differences in behavioral habits, or differences in the rates of co-morbidities. IMPLICATIONS OF KEY FINDINGS: Countries and studies should report their data by age, gender and co-morbidities. This may have implications in terms of vaccination strategies, the choice of treatments and future consequences for long-term health issues concerning gender equality.

Attitudes to the prescription of menopause hormone therapy for vasomotor symptoms and osteoporosis for patients of different ages: A survey of gynecologists in Belgium.

INTRODUCTION: The interpretation of the literature on menopause hormone therapy (MHT) has evolved enormously over the last decade. In recent years, guidelines have reinstated the place of MHT. AIM: This survey analyzes the prescription (initiation and maintenance) of MHT in relation to patient age and therapy indications. MATERIAL AND METHOD: Two vignettes were sent to gynecologists working in Belgium in a random survey. One vignette concerned the initiation of therapy for a woman who was either 52 or 62 years old, suffering either from severe vasomotor symptoms (VSM) or from osteoporosis. The second vignette concerned the maintenance of MHT or switching to another medication in a woman aged 62 years who suffered either from VSM (when stopping MHT) or from osteoporosis. The physicians were asked how they would treat these two patients. RESULTS: We analyzed 443 vignettes from 222 physicians. INITIATION OF MHT: 84% of the respondents would initiate MHT for a 52-year-old woman with VMS, whereas only 32% would do so for a 52-year-old woman who had osteoporosis (chi square = 33; p < 0.001). 51% would initiate MHT for a 62-year-old woman with VMS, whereas only 14% would do so for a 62-year-old woman with osteoporosis (chi square = 17; p < 0.001). MAINTENANCE OF THERAPY: 87% would maintain MHT for a 62-year-old woman with severe VMS and 52% would do so for a 62-year-old woman with osteoporosis (Chi Square 31; p < 0.001). CONCLUSION: VMS are recognized as an indication for MHT, but osteoporosis much less so, even for women around the age of 50.

More women gynecologists in Belgium: assessment of changes in the workforce-a survey.

CONTEXT AND OBJECTIVE: International data highlight the increasing participation of women in the workforce in the medical field and particularly among obstetricians and gynecologists (OB-GYN). Some studies reported a gender difference in work productivity and practice patterns. The aim of this study is to analyze whether disparities exist between male and female OB-GYN in their practices with potential consequences for the organization of the OB-GYN departments. METHODS: A survey of all active, Belgian OB-GYNs concerning their professional activity and well-being and a survey of the heads of OG departments evaluating the impact of feminisation on their department. RESULTS: The response rate was 43% (n = 615). Women and men worked a similar number of half-days per week, respectively, 10.1 ± 2.4 and 10.3 ± 3.2 (p = 0.26) but women treated less patients per week (80 versus 90, p = 0.034). Pear year, women and men perform, respectively, 108 and 184 surgical procedures (p = 0.0001) plus 114 and 100 deliveries (p = 0.09). Female OB-GYNs have fewer children but the size of their family has no bearing on work hours. Qualitatively, most OB-GYN regardless of their gender, consider their profession to be gratifying. Dissatisfaction is related to organizational concerns for women and to pressure of competitiveness for men. Women are more concerned about their private life and men more focussed on their professional career. However, both expressed the primary importance of good health and quality of life. A majority (66%) of head of departments do not consider that the feminisation of their staff is problematic. CONCLUSION: There was no difference in time spent at work between male and female OB-GYN. The number of patients treated by female OB-GYN per week is smaller which means that the time spent per patient is higher. The OG profession does not appear to be jeopardized by its feminisation according to this study and the opinion of the head of departments. Nevertheless, we need to take into account when organizing the future workforce that women tend to focus more on the time spent with patients than on surgical procedures.

The use of selective progestin receptor modulators (SPRMs) and more specifically ulipristal acetate in the practice of gynaecology.

This review discusses the development of selective progestin receptor modulators (SPRMs) for use in women's health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.

In vitro fertilization for women infected by hepatitis C virus: a matched case-control study and a systematic literature review.

PURPOSE: The aim of this study was to investigate whether infection of women by the hepatitis C virus (HCV) reduces the chance of conceiving after in vitro fertilization (IVF). METHODS: We performed a retrospective blind matched case-control study where IVF outcomes for the first 37 cycles of HCV sero-positive women were compared to those of 107 cycles of an uninfected control group. Our results were included in a systematic literature review. RESULTS: Out of five eligible studies, ours included, three observed an impact of HCV infection, though at various levels including response to stimulation, fertilization, implantation, and pregnancy rates. Two studies differentiated results for patients with confirmed active viral replication. Matching criteria and populations studied varied between studies. CONCLUSIONS: More and larger studies with well-defined groups are needed to clarify the eventual impact of the HCV on IVF outcomes. Data concerning the infectious status of a patient as well as her health state should be systematically recorded. A multi-disciplinary approach as well as a thorough knowledge of the patient's general health state might prove useful in the management and counseling of these patients in terms of success in conceiving.

Medical or surgical management of fibroids? An internet survey of gynecologists' views.

AIM: To assess the attitudes of gynecologists toward symptomatic fibroids and analyze which factors influence their choice of treatment. MATERIAL AND METHOD: We surveyed the attitude of Belgian gynecologists toward patients' cases. We used a vignette of a woman with symptomatic fibroids and modified 3 factors: her age, her parity and her desire for pregnancy, thereby establishing 12 different cases. We ensured that each gynecologist (n=1437) received one case, chosen randomly, by email. The gynecologists were asked whether and how they would treat the patient. RESULTS: Replies were received from 337 gynecologists (a 23% response rate). Of the 337, 116 (34%) would prescribe a medical treatment only; in this group, 29% specified acetate ulipristal a selective progesterone receptor modulator (SPRM) and 27% indicated progestins. Of the sample of 337 responders, another 116 (34%) would begin with medical treatment (70% an SPRM) and then proceed to surgery. Of the 337 gynecologists, 75 (22%) would perform surgery only. The preferred surgical treatments were myomectomy (53/75; 71%) and hysterectomy (19/75; 25%) when surgery was suggested as a first step, and myomectomy (91/115; 79%) and hysterectomy (18/115; 16%) when it was preceded by medical treatment. The choice of treatment varied significantly in relation to the 12 vignettes (p<0.01). When we grouped the vignettes there was no significant variation in relation to age or parity, but a there was significant variation (p<0.001) in relation to desire to achieve pregnancy. CONCLUSION: We observed that, in women with symptomatic fibroids, the desire retain fertility is respected. Moreover, SPRM is increasingly used for symptomatic patients.

Real-time in-vivo microscopic imaging of the cervix using confocal laser endomicroscopy: preliminary observations and feasibility study.

Confocal laser endomicroscopy (CLE) enables in-vivo, real-time, imaging of tissues with a micron-scale resolution through a fiber optic probe. CLE could be a valuable tool for the detection and characterization of suspicious (dysplastic) areas on the uterine cervix in a minimally invasive manner. This study evaluates the technical feasibility and safety of CLE on the cervix. The study also aims to create a preliminary iconography of normal and dysplastic squamous and columnar cervical epithelium. In-vivo CLE was performed on nine patients scheduled for a cervical loop electric excision procedure for high-grade superficial intraepithelial lesions. The CLE images were compared with standard hematoxylin and eosin analysis of loop electric excision procedure specimens. The histopathological diagnosis on the surgical specimen was established as per standard of care. CLE images were then reviewed by pathologists to point out specific histopathological features. pCLE of the exocervix and the transformation zone was performed successfully on seven out of nine patients. Uninterpretable images were obtained in two other cases: one using the AlveoFlex and one using the GastroFlex UHD after the application of acetic acid 2%. A total of 82.5% of the sequences recorded with the GastroFlex were suitable for interpretation. No adverse event or complications occurred. CLE enables proper in-vivo imaging of healthy and dysplastic cervical tissue. Images correlate well with the histopathological features established through traditional histology. Future blinded prospective analysis will determine the reliability of the real-time diagnosis and its potential use in the assessment and treatment of cervical lesions.

Multi-center experience of robot-assisted laparoscopic para-aortic lymphadenectomy for staging of locally advanced cervical carcinoma.

OBJECTIVES: FIGO classification is commonly used for staging of locally advanced cervical cancer. Laparoscopic para-aortic lymphadenectomy is currently used as a diagnostic tool, since we know that presence of para-aortic lymph node metastases identifies patients with poor prognosis. The application of robotics during this procedure needs to be investigated. DESIGN: Retrospective multi-center study. SETTING: Three centers participated in building one database. POPULATION: Thirty-seven patients with locally advanced cervical cancer underwent a robot-assisted laparoscopic para-aortic lymphadenectomy. METHODS: Patients were prospectively enrolled in one register. Retrospective analysis of the whole database was performed. MAIN OUTCOME MEASURES: Surgical outcomes of the robot-assisted procedure and follow-up data. RESULTS: Median number of lymph nodes collected was 27.5 (1-54) per patient. Five of 37 patients had para-aortic node metastases. The false negative rate for PET-CT diagnosing para-aortic node metastases was 11.4% (4/35). Two major intra-operative complications occurred (5.4%). Postoperative morbidity was low (13.5%). Median follow-up was 27 months [95% confidence interval (95% CI) was 24-30]. Median disease-free survival was 16 months (95% CI 2.4-29.6). Patients with negative nodes had a median disease-free survival of 24 months (not assessable), although patients with positive nodes had a median disease-free survival of 9 months (95% CI 6.9-11.9). CONCLUSIONS: In this series we report that robot-assisted laparoscopic para-aortic lymphadencetomy provided the surgeon with useful information, diagnosing 11.4% of occult para-aortic lymph node metastases in women with locally advanced cervical cancer. Intra-operative and postoperative morbidity were low. The presence of para-aortic lymph node metastases correlated with shorter disease-free survival.

Postmenopausal hormone therapy: risks and benefits.

Postmenopausal hormone therapy (PMHT) is used for the relief of menopausal symptoms, but the dosage has varied greatly throughout its existence. By the end of the 1990s, PMHT was mainly used to prevent chronic diseases such as osteoporosis, coronary heart disease and dementia, and large prevention trials were undertaken in this context. Following the initial negative reports of these trials, use of PMHT dramatically decreased. These reports noted surprisingly increased risks, notably of coronary heart disease, stroke and breast cancer, in people who used PMHT. Nowadays, considering the currently available data, it seems that an important distinction should be made between the treatment of climacteric symptoms in young, generally healthy, postmenopausal women and the prevention of chronic diseases in elderly women. PMHT seems to be beneficial and safe for postmenopausal symptomatic women aged <60 years. Treatments with a high safety profile should be the preferred option, including low-dose PMHT, oestrogen-only therapy in women who have had a hysterectomy, and vaginal oestrogen therapy for women with atrophic vaginitis. Nonandrogenic progestin might have a reduced thrombotic and breast cancer risk, and transdermal oestrogen could have a reduced thrombotic risk. Nevertheless, PMHT should not be used for the prevention of chronic diseases in the elderly (>70 years old) owing to the increased risk of stroke and breast cancer in these patients.

Determinants of the decision to perform prophylactic oophorectomy in association with a hysterectomy for a benign condition.

BACKGROUND: The decision to perform an elective bilateral salpingo-oophorectomy (BSO) at the time of a hysterectomy for a benign condition is complex. AIM: To assess the determinants of the decision to proceed to a prophylactic BSO during a hysterectomy for a benign condition. MATERIALS AND METHODS: We collected demographic and clinical data, including age, menopausal status and risk of ovarian cancer. Using a regression model we analysed the decision perform a prophylactic BSO in women successively admitted for a hysterectomy for a benign condition, in relation to the collected demographic and clinical data. RESULTS: Data were collected for 43 women, aged between 37 and 65 years (mean age 48.6 years, SD 6.9), on the day before their hysterectomy. Thirty-six (84%) had a total hysterectomy and 7 (16%) a subtotal hysterectomy; 40 (93%) had a laparoscopic procedure. Prophylactic BSO was significantly associated with age: none of the women aged under 40 years had the procedure, compared with 8% of those aged 41-45 years, 29% of those aged 46-50 years and 83% of those aged 51 years or more (χ(2)=23; P<0.001). Of the postmenopausal women, 67% had a prophylactic BSO, compared with 24% of the premenopausal women (χ(2)=6; P<0.047). In this small series of patients no relationship was found between the decision to perform a BSO and the risk of ovarian cancer. Age was the only significant variable in the regression model (pseudo R(2) Nagelkerke=0.6, P<0.05). CONCLUSION: The physician's recommendation to perform an elective BSO at the time of a hysterectomy for a benign condition is strongly influenced by the patients' age.

Factors affecting gynaecologists' decision to perform prophylactic oophorectomy concomitantly with hysterectomy: a Belgian survey.

BACKGROUND: The recommendation to perform an elective bilateral salpingo-oophorectomy (BSO) at the time of a hysterectomy for a benign condition is complex. AIM: This survey evaluated the effect of three factors on BSO: the patient's age, her menopausal status, and the presence of a family history of breast cancer. MATERIALS AND METHOD: We conducted an anonymous written survey, sent to 1513 gynaecologists, evaluating their attitude towards performing a prophylactic BSO concomitantly with a hysterectomy. We used a clinical vignette of a patient presenting a large and painful fibroid. We modified three factors: her age (either 44 or 49 years old), menopausal status (pre-menopausal or peri-menopausal), the absence or presence of a breast cancer family history. We randomly sent one case to each gynaecologist, who was asked whether he/she would perform a BSO. RESULTS: The recommendation to perform a BSO varied between 2% and 81%, in relation to the different cases (χ(2): 151; p<0.001). On average, a five year difference in the patients' age (44 years vs 49 years) was associated with a 40% increase in proceeding a BSO. Being peri-menopausal vs being pre-menopausal, was associated with a 20% increase in suggesting a BSO. Having had a mother, diagnosed with breast cancer, was associated with a 10% increase of BSO. CONCLUSION: The physicians' recommendation to perform an elective bilateral salpingo-oophorectomy at the time of a hysterectomy, is strongly influenced by the patients' age, and to a lesser extent by her menopausal status, or a family history of breast cancer.

Robotically assisted laparoscopic microsurgical tubal reanastomosis: a retrospective study.

OBJECTIVE: To evaluate the pregnancy and delivery outcome of robot-assisted tubal reanastomosis. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Ninety-seven patients with available follow-up who underwent the reversal of tubal ligation, with a median age of 37 years (range, 24-47 years). INTERVENTION(S): Tubal reanastomosis by robot-assisted laparoscopy. MAIN OUTCOME MEASURE(S): Analysis of the distribution of time to conception and to estimate the crude pregnancy and birth rates at 2 years. RESULT(S): The overall pregnancy and birth rates were 71%, (95% confidence interval [CI], 61%-80%) and 62% (95% CI, 52%-72%). Ninety-one percent (95% CI, 76%-98%) of patients <35 years old became pregnant, and 88% (95% CI, 72%-97%) delivered at least once. The corresponding pregnancy and delivery rates were 75% (95% CI, 57%-89%) and 66% (95% CI, 47%-81%) between 36 and 39 years old, 50% (95% CI, 25%-75%) and 43.8% (95% CI, 20%-70%) between 40 and 42 years old, 33% (95% CI, 10%-65%) and 8.3% (95% CI, <1%-38%) after the age of 43 years. CONCLUSION(S): This study reports satisfactory birth rates after tubal reanastomosis by robot-assisted laparoscopy in patients aged 40 years or less.

Robot assisted laparoscopic transperitoneal para-aortic lymphadenectomy in the management of advanced cervical carcinoma.

OBJECTIVES: Adequate staging of advanced cervical cancer is essential in order to optimally treat the patient. FIGO clinical staging, imaging techniques such as CT scan, MRI and PET sometimes underestimate the extension of tumors. The presence of para-aortic lymph node metastases in advanced cervical cancer identifies patients with poor prognosis who need to be treated aggressively. Laparoscopic para-aortic lymph node dissection is now proposed as a diagnostic tool in many guidelines. We evaluated the feasibility and safety of a robot assisted laparoscopic transperitoneal approach to para-aortic lymph node dissection. STUDY DESIGN: Eight patients with advanced cervical carcinoma who were eligible for primary pelvic radiotherapy combined with concurrent cisplatin chemotherapy or pelvic exenteration underwent a pre-treatment robot assisted transperitoneal laparoscopic para-aortic lymphadenectomy. RESULTS: We isolated from 1 to 38 para-aortic nodes per patient and had one para-aortic node positive patient who was treated with extended doses of pelvic radiotherapy. We did not encounter any major complications and post-operative morbidity was low. CONCLUSIONS: Robot assisted transperitoneal laparoscopic para-aortic lymphadenectomy is feasible and provides the surgeon with greater precision than classical laparoscopy. Larger prospective multicentric trials are needed to validate the generalised usefulness of this technique.

Propensity of gynaecologists towards osteoporosis management and treatment.

BACKGROUND: Regulation authorities have recently advised against the use of hormone replacement therapy (HRT) as a first choice treatment for postmenopausal osteoporosis, modifying the past consensus. AIM: Analyse the sensibility to and prescription attitude for osteoporosis. SETTING: Survey. POPULATION: Belgian gynaecologists. METHODS: Case construction: two cases to assess whether gynaecologists are prone to detect osteoporosis, and six others to evaluate their prescription attitude for osteoporosis. RESULTS: About 80% of the physicians would prescribe a bone mineral density measurement (BMD) to a 66-year-old, non HRT user. About 60% prescribed calcium and Vitamin D when the BMD was normal, 90% would prescribe it when the BMD showed osteopenia or osteoporosis (p < 0.001). Few prescribed HRT (< 25%). Few advised SERMS for normal BMD, 19%-47% prescribed it in osteopenia or osteoporosis (p < 0.001). Few considered a biphosphonate in normal BMD, or osteopenia in the absence of risk factors, 25% considered it in osteopenia in the presence of risk factors, and 80% in osteoporosis (p < 0.001). CONCLUSION: Most gynaecologists are aware of the osteoporosis problem. They often screen non HRT users and in the event of osteoporosis, they initiate a specific treatment, not HRT, but generally a combination of calcium, Vitamin D and biphosphonates.