Ultra-low dose - new approaches in menopausal hormone therapy.

Despite increasing life expectancy, the age of onset of natural menopause has not significantly changed in recent decades. Thus, women spend about one-third of their lives in an estrogen-deficient state if untreated. There is a need for appropriate treatment of acute symptoms and prevention of the sequelae of chronic estrogen deficiency. International guidelines call for the use of the lowest effective hormone dosage for vasomotor symptom relief, the major indication for menopausal hormone therapy (MHT). In 2011, an oral continuous combined ultra-low-dose MHT was approved in Switzerland. This publication was elaborated by eight national menopause specialists and intends to review the advantages and disadvantages of ultra-low-dose MHT after the first years of its general use in Switzerland. It concludes that, for many women, ultra-low-dose MHT may be sufficient to decrease vasomotor symptoms, but not necessarily to guarantee fracture prevention.

Recommendations for raloxifene use in daily clinical practice in the Swiss setting.

BACKGROUND/AIM: Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. METHODS: Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. RESULTS: Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2 × 2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. CONCLUSION: Postmenopausal women between 50 and 70 years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precautions.

[Menopause: where are we three years beyond WHI?]. / Menopause: où en sommes-nous trois ans après la WHI?

The WHI triggered a great debate on Menopausal Hormonal Therapy. We now know that HT should not be used in cardio-vascular prevention. Many studies have yet been published regarding it's influence on breast cancers. Risks should be modulated in respect with the type of treatment and the targeted population. Only recently menopaused women or women suffering from invalidating menopausal symptoms should benefit from HT. When an HT is needed, the authors recommend the use of trans-cutaneous estrogens combined with natural oral progesterone. Every HT should be prescribed individually, according to the patient's aspirations and expectations.

Biliary calculi caused by hemobilia.

Formation of biliary calculi caused by hemobilia is rare. Including the two cases reported here, there are only a total of four in the literature. The characteristics of these calculi in vitro, on computerized tomographic scan, and cholecystography are described. The condition for the occurrence seems to be that blood clots remain in the gallbladder sufficiently long (about 6 months) to become encrusted with bile constituents. Patients with hemobilia with clots in the gallbladder should be observed for this complication.

Nonclosure of the visceral and parietal peritoneum at caesarean section: a randomised controlled trial.

OBJECTIVE: To assess the short term morbidity of nonclosure of the peritoneum at caesarean section. DESIGN: Women undergoing a lower segment caesarean section were randomly allocated to either closure or nonclosure of the visceral and parietal peritoneum. SETTING: Tertiary Care University Hospital of Geneva. MAIN OUTCOME MEASURES: Length of post-operative hospital stay. Other outcomes include maternal pain as assessed by both a visual analogue scale and the amount of post-operative analgesics administered, post-operative ileus, and febrile morbidity. Operative time was recorded. RESULTS: We allocated 137 women to the nonclosure group and 143 to the closure group. Population characteristics were similar between groups. The mean length of hospital stay was 6.5 (SD 1.9) days for the nonclosure group and 6.8 (SD 2.2) days for the closure group (P = 0.21). No differences were found in the level of post-operative pain, the number of analgesic doses given, nor in the proportion with febrile morbidity. Post-operative ileus resolved later in the closure group (P = 0.006). The mean operative time was shorter by 6 min (P = 0.006) in the nonclosure group. CONCLUSIONS: Short term post-operative morbidity and maternal pain are not increased by a shorter and more simple surgical procedure in which the peritoneum is left unsutured.

[What's new in hormone replacement therapy for postmenopausal women? I. Advantages of hormone replacement therapy (HRT)]. / Quoi de neuf dans le traitement hormonal substitutif de la ménopause? I. Avantages du traitement hormonal substitutif (THS).

Different cohort studies have shown that HRT decreases the risk of cardio-vascular (C-V) disease and the risk of bone fracture by 30 to 50%. The only controlled study (HERS study) did not show any benefit of HRT with estradiol and medroxyprogesterone (MPG) in secondary prevention. The beneficial effect of estrogens on coronary dilatation and on HDL cholesterol could be attenuated by some progestogens such as MPG but not by nomegestrol acetate. In this framework, the comparative metabolic effects of different progestogens and tibolone are described in this article. The effects of estrogens on mood and of androgens on libido are discussed. The preventive effect of estrogens on osteoporosis and on Alzheimer disease is compared to other nonhormonal treatments.

[What's new in hormone replacement therapy of postmenopausal women? II. Risks of hormone replacement therapy (HRT)]. / Quoi de neuf dans le traitement hormonal substitutif de la ménopause? II. Risques du traitement hormonal substitutif (THS).

A 50 year old woman has a 10% lifetime risk of developing a breast cancer. Depending on the duration of the treatment, HRT can increase this risk by 30 to 45%. The risk of endometrial cancer, which affects 2.3% of women, is increased even if sequential progestogens are given together with estrogens. The risk of venous thrombosis is increased 3 times. The occurrence of ictus is not modified by HRT. On the other hand estrogens may prevent the abdominal deposit of fat. The cancer risks associated with HRT must be balanced against their protective effects on cardio-vascular (C-V)diseases. In untreated women, mortality due to C-V disease is 39% whereas mortality due to breast cancer is 3% and only 0.3% for endometrial cancer. This article discusses also the possibility of HRT and of non hormonal treatments in patients with previous breast cancer.