Background. Advances in the treatment of gynecological cancer have led to improvements in survival but also an increase in menopausal symptoms, especially in young women with premature iatrogenic menopause. Methods. A narrative review was performed to clarify the possibility of prescribing hormone replacement therapy (HRT) after hormone-dependent gynecological cancers (ovarian cancer [OC], cervical adenocarcinoma [AC], and endometrial cancer [EC]). Results. HRT can be prescribed to patients with early-stage, grade I–II OC who experience bothersome menopausal symptoms non-responsive to alternative non-hormone therapy after optimal surgery. Caution should be exercised in administering HRT after serous borderline tumors and endometrioid OC, and HRT is not recommended in low-grade serous OC. HRT is not contraindicated in AC survivors. After surgery for EC, HRT can be prescribed in women with early-stage low-grade EC. There is not enough data to give indications to patients with advanced EC. Conclusions. HRT can be discussed with patients, evaluating the risks and benefits of hormone-dependent gynecological cancer. Counseling should be performed by gynecologic oncologists experienced in the management of these patients.

Background and Objectives: Data emerging from the Women’s Health Initiative (WHI) study point toward an association between menopausal hormone therapy (MHT) and cardiovascular (CV) risk. However, post hoc subgroup analyses stratifying participants according to their age and time since menopause, have opened the way to a better understanding of the relationship between estrogen and CV risk. The aim of this review was to revise the current literature and evaluate the CV risk or benefit following administration of MHT considering several factors such as MHT timing, dose, route of administration, and formulation. Materials and Methods: An electronic databases search of MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) was performed, with the date range from each database’s inception until June 2019. All the studies evaluating MHT and cardiovascular risk, including thromboembolism or stroke, were selected. Results: Timing of MHT initiation was shown to be a critical factor in CV risk assessment. In concordance with the “timing hypothesis”, healthy symptomatic women who initiated MHT when aged younger than 60 years, or who were within 10 years of menopause onset, have demonstrated a reduction in both coronary heart disease (CHD) risk and all-cause mortality. In particular, MHT therapy was associated with improvement of subclinical signs of atherosclerosis. Venous thromboembolism (VTE) risk is reduced when low doses of oral estrogen are used. Moreover, transdermal hormonal application significantly reduces CV risk compared with oral administration. MHT impact on the CV system is influenced by either factors inherent to the specific regimen, or factors inherent to the specific patient. Hence, individualization of care is necessary. Conclusion: CV risk calculation should be considered by clinicians in order to exclude patients with high CV risk, in whom MHT is contraindicated. Assessing risks and benefits in a patient-centered approach according to individual’s features, health status, and personal preferences is important in order to realize a safe and effective treatment.

Vulvo-vaginal atrophy (VVA) is a chronic condition affecting many postmenopausal women. Local estrogen treatment is recommended. Evaluating efficacy and safety of long-term VVA treatment with ultra-low-dose estriol gel, 120 postmenopausal VVA women were enrolled in a prospective study. They received the first cycle of 1 g/day vaginal gel containing 50 µg estriol for 3 weeks and then twice a week for 12 weeks. Moderate or severe VVA women received a second treatment cycle reaching treatment of 30 weeks. Vaginal pH measurement, subjective symptoms, and objective signs assessment of VVA, endometrial thickness and adverse events (AE) were recorded. Of the 99 women, completing the first phase, 43% experienced a complete VVA symptom relief, and 65% presented a milder VVA degree. After 30 weeks, VVA signs significantly improved (p<.01) compared with baseline and first phase results; total objective symptom evaluation including Schiller’s test, flattening of folds and vaginal pH significantly improved (p<.01). At study endpoint, none of the patients had severe VVA, 93% had a positive response, 75% had a complete symptom, and sign resolution. No treatment-related endometrial AE were observed. Postmenopausal VVA long term-treatment with ultra-low-dose estriol vaginal gel is safe and effective.

Breast cancer (BC) survivors often experience vulvovaginal atrophy (VVA) due to endocrine therapies, affecting quality of life (QoL) and well-being. We aimed to evaluate impact of ospemifene treatment in postmenopausal women with history of BC and moderate to severe VVA. PEONY is a real-world, prospective, multicenter study. Participants completed questionnaires at baseline, after 3 and 6 months. Treatment satisfaction score was the primary outcome. As secondary outcomes, symptoms severity, day-to-day impact of vaginal aging scale, female sexual function index, female sexual distress scale-revised, and SF-12® Health survey were investigated. Sixty-four women with a mean age of 56.4 ± 7.2 years (41.9% with severe VVA) either initiated (35.9%) or continued (64.1%) ospemifene. Treatment satisfaction significantly improved over 6 months, with mean score rising from 7.1 to 7.8 (P = .047). The odds of moderate to severe symptoms, such as vaginal dryness, pain and bleeding during sexual intercourse, genital discomfort during physical activity, burning, and itching, decreased by 70% to 90% at 6 months, as well as recurrent urinary tract infections and cystitis associated with sexual intercourse (by 80% and 90%). QoL measurements showed significant improvements in physical health and daily functioning, although mental health improvements were not statistically significant. Likelihood of sexual distress decreased by 40%. Although overall sexual function remained unchanged, specific domains such as lubrication and pain showed improvement. Ospemifene is effective and well-tolerated for treating moderate to severe VVA of women with history of BC. However, a comprehensive and multidisciplinary approach is needed to improve sexual function of BC survivors treated for VVA.