Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial

Background Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. Methods The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. Discussion This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853. EudraCT: 2017-003144-21; registered: 24-07-2017.

MENOPAUSAL HORMONAL THERAPY AND BREAST CANCER

Наиболее распространенным методом лечения климактерического синдрома является менопаузальная гормональная терапия (МГТ), однако безопасность ее применения, в связи с риском развития и рецидива рака молочной железы (РМЖ), до сих пор является предметом дискуссии. В обзоре приводятся результаты рандомизированных контролируемых исследований этой проблемы. Показано, что МГТ повышает риск развития РМЖ и рецидива заболевания после лечения. Риск РМЖ, развивающегося у женщин, получающих МГТ, зависит от ИМТ, длительности приема и дозы препаратов и выше у худых женщин, чем у женщин с повышенным ИМТ, а также выше у женщин, принимающих комбинированную МГТ (эстроген и прогестаген), по сравнению с женщинами, принимающими только эстрогенную терапию. Обнаружено, что у женщин, принимавших МГТ, чаще развивались гормонозависимые формы рака, но к моменту диагностики заболевания выявлялись более распространенные стадии и чаще обнаруживались метастазы в лимфатические узлы по сравнению с женщинами, не принимавшими МГТ. Риск рецидива РМЖ меньше при применении низких доз вагинального эстрогена. Альтернативным вариантом купирования менопаузальных расстройств у пациенток на фоне и после лечения РМЖ может стать применение гормона эпифиза мелатонина, поскольку наряду с его геропротекторными свойствами он способен подавлять рак на этапах инициации, прогрессирования и метастазирования и обладает способностью уменьшать токсические последствия противоопухолевых препаратов при одновременном повышении их эффективности. The most common treatment for menopausal syndrome is menopausal hormone therapy (MHT), however, the safety of MHT, due to the risk of developing and recurrent breast cancer (BC), is still a matter of debate. The review presents the results of randomized cohort studies of this issue. It has been shown that MHT increases the risk of developing of breast cancer and disease recurrence after treatment. Risk of breast cancer developing in women getting MHT, depends on body mass index (BMI), duration of hormone use and dose of drugs, and is greater in thin women comparing with women with increased BMI, and also greater in estrogen-progestin combined MHT users comparing with estrogen-only users. It was found that in women using MHT hormone-dependent forms of cancer developed more often, but by the time of diagnosis, disease was found in more advanced stage and metastases in lymph nodes were found more often comparing with patients who did not use MHT. Risk of breast cancer recurrence is less with the use of low doses of vaginal estrogen. An alternative option for the relief of menopausal disorders in breast cancer patients during and after treatment is using of pineal gland hormone melatonin, since, along with its anti-aging properties, it is able to suppress cancer at the stages of initiation, progression and metastasis and has the ability to reduce the toxic effects of anticancer drugs while increasing their effectiveness.

A Rare Case of Autoimmune Progesterone Disease

Background: Autoimmune progesterone disease is a rare disease, with fewer than 200 reported cases. Unfortunately, there are no published estimates of incidence or prevalence. Clinical Case: A 24 year-old woman with no significant past medical history presented with sudden and new onset swelling of the lips which was unresponsive to Benadryl and prednisone. Swelling eventually progressed into blistering over the lips, oral, pharyngeal mucosa and tongue. She was admitted to the hospital for suspicion of Steven Johnson syndrome and was discharged after resolution of skin and oral lesions following treatment. She presented again in 3 months with full body rash and blisters now involving oral and vaginal mucosa. She underwent biopsy of these lesions during this admission and findings were suspicious for drug eruption vs erythema multiforme. Unfortunately, inciting drug or event could not be associated even with pathological diagnosis. She continued to have mucocutaneous flare every month for the next 8 months with multiple hospitalizations and was treated with antibiotics during these admissions. Over the course of her evaluation, it was noted that her symptoms seemed to coincide with her menstrual cycles. Her IUD was removed and she was started on OCPs but her symptoms persisted without any improvement. She underwent intradermal progesterone challenge test at tertiary center for ongoing cyclical dermatitis and tested positive for progesterone sensitivity. She was diagnosed with Autoimmune Progesterone dermatitis. She had to ultimately undergo total abdominal hysterectomy and bilateral salphingo-oophorectomy as she failed OCPs and had adverse effects to progesterone desensitization including full body rash and blisters. Post operatively, she has been started on IM depot injections of estrogen and vaginal estrogen cream. Conclusion: Autoimmune progesterone disease also known as progesterone dermatitis or progesterone hypersensitivity is not associated with other autoimmune diseases and usually affects women of reproductive age. It is a rare disorder with variable presentation and often overlaps with other forms of dermatosis. It is commonly underdiagnosed or misdiagnosed and appropriate treatment is often delayed. High clinical suspicion for symptoms of cyclical nature is necessary for making the diagnosis.