Dose Of Progestogen Research Articles

8131 A Rare Case of Autoimmune Polyendocrine Syndrome; a Menopause Despite Replacement Therapy

Abstract Disclosure: M.E. Chacon Cruz: None. M. Sanchez Cordero: None. R.M. Roman Torres: None. G. Guerra Velazquez: None. Polyendocrinopathy is a heterogeneous group of disorders leading to dysfunction of multiple endocrine glands and other tissues. The syndromes can occur in patients from early infancy to old age and new components of a given syndrome can appear throughout life. APS can be classified into APS type 1 and APS2-4. APS-1 is a rare monogenic autosomal recessive autoimmune disorder consisting of the triad of chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. APS2 require presence of Addison disease, autoimmune thyroid disorder and type 1 diabetes. APS 3 requires presence of Thyroid autoimmune disease associated with other autoimmune diseases. APS4 is a combination of organ specific autoimmune disease non included in a previous group. Autoimmune oophoritis is found in approximately 4 percent of females who presented with spontaneous primary ovarian insufficiency and may occur in type I and II syndromes of polyglandular autoimmune failure. This is the case of 44 year old female patient with history of hypertension, hypoparathyroidism diagnose at the age of 9 year old, vitiligo and premature ovarian failure diagnose at the age of 16 year old. Patient reported that started with multiple episodes of watery non bloody diarrhea and arthralgia. Patient went to her Pediatrician and they found hypocalcemia hyperphospathemia. Patient mineral was replaced with medication and then followed by pediatric endocrinologist. Patient continues with normal life, but menstrual periods had not started even at age 16th. Laboratory work up was done and premature ovarian failure was diagnosed after that, patient started with progesterone and estrogen to induce menstrual periods. Menstrual periods began regularly and monthly. Patient continues taking medication regularly, phoslo, calcitriol, progestin and estradiol without problem until this year that despite regular medication, started with signs and symptoms of menopause with irregular menstrual periods, palpitations hot flashes, sweating, anxiety and sleep problems. Patient met criteria for APS4 due to combination of organ specific autoimmune disease such premature ovarian failure, vitiligo and hypoparathryroidism. This case is extremely important since despite the fact that there is no family history of either endocrinological or autoimmune diseases, our patient debuts throughout her life with several autoimmune diseases, such as premature ovarian failure and vitiligo. Patient had Schedule appointment with gynecologist who increased the dose of progestin and estradiol. This case highlights the importance of being vigilant about new components of a syndrome developing at different times though a patient's life. As described, autoimmune diseases commonly are related to other diseases, but without a good clinical history and physical examination could be misdiagnosed affecting the quality of life of those patients. Presentation: 6/2/2024

O-011 Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Efficacy of natural progesterone

Abstract Study question Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Summary answer Inhibition of the LH surge by progesterone during the luteal phase of duostim protocols in POR appears to be effective, safe and makes GnRH-antagonists unnecessary. What is known already High levels of progesterone have long been shown to reversibly block the LH surge associated with increased estradiol levels, by reducing GnRH’s pulsatility from the hypothalamus. This inhibition is the basis of progestin-only contraceptives and has been shown to be completely reversible by discontinuing the progestin, and even seems to have a potentiating effect on the surge which occurs in the subsequent few days Study design, size, duration This is a secondary analysis of the BISTIM study, a multicentre, open-labelled randomized controlled trial, performed in 4 french IVF centers from 2018 to 2021, designed to compare Duostim protocol versus two follicular stimulations. We here present a paired-controlled study including patients randomized in the Duostim group, who underwent 2 consecutive stimulations in the same menstrual cycle, we compare the follicular phase stimulation with GnRH-antagonist versus the luteal phase stimulation with progesterone. Participants/materials, setting, methods The BISTIM study recruited poor ovarian reserve women defined with Bologna criteria who enrolled in an IVF or ICSI program, aged from 20 to 41, with BMI from 19 to 32, with no more than 2 previous IVF cycles. Women with amenorrhea, FSH >20 UI/L or CFA <1 were not included. 32 of them underwent two stimulations, consecutively. Main results and the role of chance For the same group of 32 women, stimulation parameters were similar between 1st and 2nd stimulations (stimulation duration, gonadotropin doses, number of retrieved oocytes). As expected, progesterone levels were significantly higher at D5 in the study group compared to controls (mean 34.8 ng/ml, Q1-Q3 [18.4 – 51.6])) and were still significantly higher at HCG-day (10.7 ng/ml, Q1-Q3 [2.7 – 14.3])), despite the addition of natural exogenous progesterone. LH levels were significantly lower in the progesterone group, regardless of the day of stimulation: at HCG day mean LH was 1,7 UI/L in the study group versus 6.8 UI/L in the control group, p < 0.001. In the Duostim group no premature LH surge/ovulation was observed, however, 2 cancellations for premature ovulation were reported with antagonist protocol in the control group of the BISTIM study. Limitations, reasons for caution This study was carried out on a limited number of subjects (n = 32), all of whom were poor responders. Wider implications of the findings This study shows the effectiveness of LH surge inhibition by progestins, which represent a less expensive and more patient-friendly treatment than traditional protocols. Further studies are needed to determine the best protocol (type and doses of progestins) to effectively inhibit the LH surge, and on larger and different cohorts. Trial registration number 2017-A00498-45

Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Individuals with Turner Syndrome

Study ObjectiveIncidence of abnormal uterine bleeding (AUB) during pubertal induction among individuals with Turner syndrome (TS) has not been described previously. We estimated the incidence and characterized factors associated with AUB among individuals with TS. A secondary objective was to evaluate the management of AUB among this patient population. Design, Setting, Participants, and InterventionWe conducted a retrospective chart review to evaluate individuals with TS undergoing hormone replacement therapy (HRT) for pubertal induction with transdermal estrogen. A total of 45 participants were identified between January 2007 and June 2019. ResultsOf the 45 individuals with TS included, 16 (35%) experienced AUB. Individuals with AUB most commonly experienced prolonged (44%), prolonged and heavy (25%), and intermenstrual (19%) bleeding. Individuals who experienced AUB were more likely to experience spontaneous bleeding (69% vs 28%) and a duration of unopposed estrogen greater than 18 months (63% vs 41%), undergo progestin cycling less often than monthly (69% vs 0%), use a micronized progestin dose of less than 200 mg (25% vs 14%), and be noncompliant with HRT (19% vs 0%) compared with those who did not experience AUB. ConclusionThere is a relatively high incidence of AUB among individuals with TS undergoing pubertal induction with transdermal estrogen. Care providers should consider the clinical factors examined to guide monitoring and management of individuals with TS on HRT.

7389 Progesterone Hypersensitivity: Challenges in Longitudinal Care Management. A Case Report

<h3>Study Objective</h3> Progesterone Hypersensitivity. Challenges of Longitudinal Case Management. A case report. <h3>Design</h3> A case report. <h3>Setting</h3> Clinical practice in a community setting. <h3>Patients or Participants</h3> 19-year-old patient with 6-year history of Progesterone Hypersensitivity. <h3>Interventions</h3> Drosperinone contraception, GnRH Agonist with estradiol add-back; Hysterectomy with oophorectomy. <h3>Measurements and Main Results</h3> Patient experienced menarche at age 11. Her second menstrual cycle occurred at age 13 and was accompanied by anaphylactic episodes requiring four single-use epinephrine injections. She was immediately placed on an oral contraceptive of ethinyl estradiol and the 19-nortestosterone-derived progestin, norgestimate, but she required six epinephrine administrations for anaphylactic episodes in her next cycle. Her allergist referred her to the presenting author, who immediately switched her to continuous drosperinone/ethinyl estradiol contraception. (Drosperinone is a spironolactone analogue progestin.) This rapidly controlled the anaphylactic episodes. Over the next 6 years, rare anaphylactic episodes occurred with formulary substitution to generic drosperinone preparations. A large, framed woman, she required 6 mg of drosperinone daily when her weight exceeded 85 Kg. She was counseled on long-term treatment options including progesterone desensitization and GnRH agonist therapy with add-back estradiol. Psychosocial aspects of her options including reproductive options were counseled. After an 8-month trial of GnRH with add-back estradiol, she underwent robotic laparoscopic total hysterectomy with bilateral salpingo-oophorectomy. Findings at time of surgery included endometriosis of the left utero-sacral ligament (AAGL score = 2 points). The patient is very happy with her surgical outcome. Vasomotor symptoms are being treated. <h3>Conclusion</h3> Progesterone Hypersensitivity in the patient arose with her second menstrual cycle. Effective management of her condition required (1) hypothalamic suppression of ovulation, by reliable doses of the spironolactone analogue progestin, drosperinone, or by GnRH agonist, (2) adequate social support and (3) consideration of hysterectomy and oophorectomy.

Иммуногистохимическая оценка эффективности лечения пациенток репродуктивного возраста с аномальными маточными кровотечениями и гиперплазией эндометрия

Objective. Immunohistochemical analysis of the efficacy of progestin therapy for endometrial hyperplasia (EH) without atypia in female patients of reproductive age. Patients and methods. The study included 101 female patients of reproductive age with abnormal uterine bleeding who were diagnosed with EH without atypia after histological examination of the endometrium. These patients were treated with standard doses of progestins between days 5 and 25 of their menstrual cycle for 6 months. After the end of hormone therapy, aspiration biopsy of the endometrium was performed. Immunohistochemical examination of endometrial biopsy was performed in addition to histological examination in 54 patients before and after therapy: the expression of progesterone (PR-A, PR-B) and estrogen receptors (ERα) and the Ki-67 proliferative index were determined. The control group included 18 women without endometrial pathology. Results. Therapy was effective in 77 patients with EH (the menstrual cycle was normalized, the endometrium corresponded to the menstrual phase at pelvic ultrasound and histological examination of uterine aspirate); EH was still present in 24 patients. Immunohistochemical examination of the endometrium in patients without the effect of progestin therapy initially revealed lower expression of ERα in endometrial glands, PR-A and PR-B in endometrial stroma and glands, and a higher Ki-67 proliferative index in endometrial stroma; their expression did not change after therapy. In patients with a positive effect of hormone therapy, the expression of ERα in endometrial glands, PR-A and PR-B in endometrial stroma and glands increased and approached the values of healthy women in the control group. Conclusion. Patients with EH and positive effect of progestin therapy had higher values of the expression of ERα in endometrial glands, PR-A and PR-B in endometrial stroma and glands, and a lower Ki-67 proliferative index in endometrial stroma, which suggests that these parameters may serve as predictors of the efficacy of therapy for EH with gestagen-containing medications. Key words: abnormal uterine bleeding, progestagens, endometrial hyperplasia, immunohisto-chemical examination, Ki-67 proliferative index, endometrial pathomorphology, progesterone receptors, estrogen receptors

First-trimester miscarriage in the background of endometrial carcinoma

BackgroundEndometrial cancer in young women (less than 40-year-old) is associated with anovulatory menses, polycystic ovarian syndrome (PCOS) and subfertility. Endometrial cancer occurring in a miscarriage is rare. We highlight a case of endometrial cancer occurring during miscarriage of a non-viable pregnancy, its management and the outcome. CaseA 32-year-old woman, Gravida 1 Para 0, was referred to our center at 7 weeks gestation in 2018 for uncontrolled diabetes mellitus diagnosed during investigation for subfertility. Her poor compliance with the treatment is consistent with an HbA1c of 8%. During the assessment, she was already complaining of lower abdominal pain. Ultrasound showed irregular IUGS with no fetal echo. She had a miscarriage soon; however, due to ultrasound evidence of thickened and irregular endometrium (17 mm) with mixed echogenicity, dilatation and curettage (D + C) were commenced. The first and second tissues were reported as the product of conception (POC) and well differentiated endometrioid adenocarcinoma, respectively. The first hysteroscopy showed foci area of polypoidal growth at the right posterior endometrium, obscuring the right ostium, with similar histology report. She was commenced on high-dose progestogen with hysteroscopy surveillance 6 months later, which showed disease regression. After two normal hysteroscopies and endometrial biopsies with continuous progestogen therapy for 12 months, cyclical progestogen for 12 months and follow-up for another 6 months, she had spontaneous conception and is currently pregnant at 16 weeks gestation. ConclusionEndometrial cancer should be suspected in high-risk patients with first-trimester miscarriage. Individualized treatment with high dose progestogen and follow-up with the proper patient and partner counselling and education has high successful regressionand later on, pregnancy rate.

Non-Contraceptive Progestins and Risk of Venous Thromboembolism: A Nested Case-Control Study of the Marketscan Databases

<h3>Study Objective</h3> To evaluate for a dose-response relationship in the association between progestins used for non-contraceptive indications (e.g., endometriosis) and venous thromboembolism (VTE). <h3>Design</h3> Nested case-control study. <h3>Setting</h3> The IBM® MarketScan® Databases include routinely collected inpatient, outpatient, and pharmacy claims data among privately insured individuals in the US. <h3>Patients or Participants</h3> Records of 45 million women aged 15-49 years old were evaluated from 2009-2018. Cases with VTE (n=21,405) were identified by validated ICD-9/10 codes and excluded for recent pregnancy, recent estrogen prescription, or indications for ultra-high dose progestins (e.g., endometrial intraepithelial neoplasia). Controls (n=107,025) were individually age-matched 5:1 by risk set sampling. <h3>Interventions</h3> N/A. <h3>Measurements and Main Results</h3> Oral progestin exposures and covariates were defined by prescription claims and ICD-9/10 codes, respectively, within 1 year before the index date. Multivariate conditional logistic regression models determined odds ratios with 95% confidence intervals adjusted for VTE risk factors. The dose-response relationship was assessed by two separate exploratory analyses. The first analysis compared new and chronic use with non-use. The second analysis evaluated progestin exposure as a weighted average daily dose. Significance was set at p<0.01 to allow for multiple comparisons. Odds of VTE were significantly increased for current use of norethindrone acetate (new users aOR 4.97 [2.96-8.35], n=83; chronic users aOR 2.28 [1.48-3.51], n=118) and current use of medroxyprogesterone acetate (new users aOR 2.08 [1.47-2.96], n=194; chronic users aOR 1.76 [1.18-2.63], n=145), compared with non-use. Comparisons between new and chronic use were not significant. Odds of VTE were directly proportional to progestin dose: +22% (aOR 1.22 [1.09-1.36]) for each 2.5 mg/day increase in norethindrone acetate and +19% (aOR 1.19 [1.08-1.30]) for each 5 mg/day increase in medroxyprogesterone acetate. <h3>Conclusion</h3> Non-contraceptive progestins are associated with increased VTE risk. This study provides the first assessment and support of the dose-response relationship. Clinicians should consider using the lowest effective dose to balance risks and benefits.

44. Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Turner Syndrome: Experience from a Large Turner Syndrome Center

<h3>Background</h3> More than 80% of girls with Turner syndrome (TS) experience primary ovarian failure prior to the onset of menarche. Hormone replacement therapy (HRT) is recommended to start between 11-12 years of age, followed by titration to adult dosing over 18-24 months. Current guidelines recommend that HRT starts with transdermal estradiol, followed by the addition of oral progesterone once breakthrough bleeding occurs or after 18-24 months of unopposed estrogen therapy, whichever occurs first. In our TS population, several individuals have experienced abnormal uterine bleeding (AUB) while undergoing pubertal induction with transdermal estradiol. The objective of this study was to identify risk factors associated with and evaluate the management practices of AUB during pubertal induction among females with TS. <h3>Methods</h3> A retrospective case series of 45 TS females seen between January 2007 and June 2019 . Among these, 64% (n=29) served as controls and 55% (n=16) experienced AUB. <h3>Results</h3> Several risk factors for the development of AUB were identified: frequency of progestin cycling less than monthly (56.5% for cases vs. 0% for control), prolonged duration of unopposed estrogen (median of 21 months for cases vs. 17 months for controls), low dose (<200 mg) of progestin (50% of cases vs. 13.5% of control), and noncompliance with HRT (18.8%). Of the patients who experienced AUB, 3 received an additional 10 day course of progestins, 7 were treated by increasing their progestin dose, 6 were switched to another method of HRT (e.g. IUD or OCP), 6 increased cycling frequency to monthly, 4 required hospitalization, 2 required iron supplementation, and 2 required a transfusion with blood products. <h3>Conclusions</h3> Based on our experience, we recommend the following to prevent AUB during pubertal induction with transdermal estrogen in TS girls: 1) Cycle with progestins monthly, 2) Introduce progestins at the onset of breakthrough bleeding or at 18 months, whichever occurs first, 3) Use progestin dosing at the upper end of the recommended range (e.g. 200 mg for micronized progesterone) 4) Counsel all patients regarding the risk of AUB, 5) Monitor all patients regularly during pubertal induction, 6) Monitor with heightened surveillance those patients who show rapid development of secondary sex characteristics on low dose estrogen.

Depot-Medroxyprogesterone Acetate Use Is Associated with Decreased Risk of Ovarian Cancer: The Mounting Evidence of a Protective Role of Progestins.

Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered. The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case-control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted. Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50-0.85). There was a statistically significant trend of decreasing risk with increasing duration of use (P trend < 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk. DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted. The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect.

Postmenopausal Bleeding: An Update

The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia and to find out the real source. Postmenopausal bleeding is ‘endometrial cancer until proven otherwise’, although only 1-14% of such patients will actually have cancer. Clinical risk factors of endometrial carcinoma such as obesity, unopposed estrogen use, polycystic ovary syndrome, diabetes mellitus and family history of gynaecologic malignancy also should be considered during evaluation. Postmenopausal bleeding usually attributed to an intrauterine source, but it may arise from the cervix, vagina, vulva or fallopian tubes &amp; ovaries. The origin of bleeding can also involve non-gynaecologic sites, such as the urethra, bladder, anus/rectum/bowel, or perineum.&#x0D; Meticulous history and thorough physical examination are must. Initial evaluation is by TVS, if endometrial thickness (ET) is &lt;4mm no further evaluation is required but follow up consultation must. If ET is&gt; 4mm, hysteroscopic evaluation and endometrial sampling is recommended&#x0D; Blind endometrial sampling is not accurate as only reveals when endometrial cancer exceeds more than 50% of the endometrial surface area so may be done if hysteroscopic evaluation is not possible. Higher dose of progesterone may be required for endometrial protection when higher doses of estradiol as hormone replacement therapy are used, or in women with high BMI. Unopposed estrogen therapy is associated with a duration and dose-related increase in risk of endometrial hyperplasia and cancer. Endometrial protection requires an adequate dose and duration of progestogen. Endometrial hyperplasia with atypia has much malignant potential but endometrial hyperplasia without atypia may be managed medically with 3 monthly endometrial sampling, if no regression or further progression hysterectomy is the choice of treatment. Finally, patient counseling with discussion of risks /benefits of different options of treatment modalities is the cornerstone of success of addressing postmenopausal bleeding.

Oral contraceptive use by formulation and endometrial cancer risk among women born in 1947\u20131964: The Nurses\u2019 Health Study II, a prospective cohort study

Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses’ Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65–0.91]; >10 years of use, 0.43 [0.32–0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 [0.41–0.67]) and second-generation progestins (0.43 [0.30–0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50–0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49–0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.

Long-Lasting, Patient-Controlled, Procedure-Free Contraception: A Review of Annovera with a Pharmacist Perspective.

Annovera (segesterone acetate and ethinyl estradiol vaginal system) is a US Food and Drug Administration FDA-approved long-lasting, reversible contraceptive that is fully administered by the user and does not require a procedure for insertion or removal. The vaginal system is in the shape of a ring and contains low doses of a novel progestin, egesterone acetate, and ethinyl estradiol. It is made of silicone and is fully pliable and flexible. The vaginal system is reusable for 13 cycles, using a 21 days in/7 days out regimen, providing women with the ability to control their fertility. Particularly now during the COVID-19 pandemic when access to contraception has been further reduced, patients may benefit from a method that is both long-lasting and patient-controlled.

Progesterone and endometrial cancer

It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.

The Review of Compared Progestins Type and Dose Utility against the Pituitary Suppression during Ovarian Stimulation for Assisted Reproductive Technology

Abstract We performed a literature review of studies comparing the effectiveness of progestins in preventing premature ovulation during ovarian stimulation for assisted reproductive technology (ART). Five randomized trials and cohort studies involving a total of 2404 women, which compared; i) two different progestins or ii) two different doses of the same progestin were included. The primary outcome was live birth rate (LBR) per woman. Secondary outcomes were live birth or ongoing pregnancy (LB/OP) per woman and per embryo transfer (ET), ongoing pregnancy, clinical pregnancy, positive pregnancy test, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotropin consumption. The primary outcome was not reported in most studies however there were no differences between progestins for secondary outcomes. All progestins seem to effectively prevent premature ovulation in ART cycles. Low-quality evidence suggests that progestins can effectively prevent premature ovulation in ART cycles.

Hormone therapy in menopausal women with fibroids: is it safe? (Literature review)

Hormone therapy is an effective treatment option for menopausal women, although prolonged use of hormone therapy is associated with a slightly increased risk of breast cancer, thromboembolism, and stroke. A literature search for studies evaluating the effects of hormone therapy in menopausal women with asymptomatic fibroids demonstrated variable effects of hormone therapy on the volume and size of the fibroids. Some studies have demonstrated an increase in size of pre-existing asymptomatic fibroids and formation of new fibroids with higher doses of progestogen in combination therapy. Selective estrogen receptor modulators having tissue-specific estrogen agonistic and antagonistic actions such as raloxifene have a favorable clinical profile and may be better alternatives in women with asymptomatic fibroids.

The Impact of Hormonal Replacement Treatment in Postmenopausal Women with Uterine Fibroids: A State-of-the-Art Review of the Literature.

Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Materials and Methods: Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Results: Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusions: For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.

Menopausal hormone therapy and cancer risks of reproductive system. Literature review

Data on risks of development of oncological diseases of bodies of reproductive system in women during menopausal transition and in a postmenopause are submitted at treatment of menopausal frustration by the preparations intended for menopausal hormonal therapy, the containing various doses of estrogen and progestogen used in the cyclic or continuous mode.

Conservative treatment in early stage endometrial cancer: a review.

Endometrial Cancer (EC) is the commonest gynecological cancer and its incidence is increasing. The diagnosis of endometrial carcinoma in young women of childbearing age is rare. Indeed, only 4% of patients with endometrial carcinoma are <40 years of age. It’s typically diagnosed in postmenopausal women. The standard approach for the management of endometrial cancer in young women of childbearing age is hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy but is not ideal for women interested in future fertility. We reviewed the published literature to clarify in fertile women who have not yet fulfilled their desire for motherhood, what are the strategies, the risks of a conservative treatment of early stage of Endometrial Cancer and what are the obstetric outcomes in this patients. Recently, several studies have reported encouraging results on fertility-sparing management of EC with high dose of progestins in selected women associated or not with hysteroscopic resection. (www.actabiomedica.it)

Impact of progestogens on hemostasis.

Combined hormonal contraception containing estrogen and progestogen and postmenopausal hormone therapy with estrogen ± progestogen are reported risk factors for venous thrombosis. The thrombotic risk varies by estrogen dose and type of progestogen. Estrogen combined with "newer generation" progestogens in combined oral contraceptives may have higher thrombotic risk than estrogen combined with older generation progestogens. Among postmenopausal women thrombotic risk also varies by type of hormone and mode of delivery. Although the risk of thrombosis with the different hormonal compounds is uncertain, it has definitely been attributed to the pharmacological effect of the hormones on hemostasis. Animal and cell culture studies have demonstrated the pharmacodynamics of progestogens with respect to hemostasis. Extrapolation from these studies to clinical conditions and further to clinical end points such as cardiovascular disease is, however, controversial. Few clinical studies have focused on the effect of progestogen only therapy on the hemostatic system in vivo. Most of the current knowledge regarding the in vivo effect of progestogens on hemostasis is obtained from studies with combined contraceptives. These results obviously reflect the combined influence of both estrogen and progestogen on hemostasis, and extrapolation to progestogen-only conditions is challenging. This paper discusses the pharmacodynamics of progestogens in relation to the hemostatic system, addressing results obtained in animal and cell culture studies and in clinical studies employing progestogen-only and combined oral contraceptives. The compiled results suggest that the major effect of progestogens on hemostasis is related to alterations in platelet function and the tissue factor pathway of coagulation. More studies focusing on these topics are warranted.

Hormone therapy in menopausal women with fibroids: is it safe?

Menopause is an important transition in the life of women. It has been estimated that by the year 2030, worldwide 1.2 billion women will be menopausal. The most bothersome symptoms of menopause are believed to be due to declines in estrogen levels in postmenopausal women. Thus, hormone therapy is an effective treatment option for menopausal women, although prolonged use of hormone therapy is associated with a slightly increased risk of breast cancer, thromboembolism, and stroke. A literature search for studies evaluating the effects of hormone therapy in menopausal women with asymptomatic fibroids demonstrated variable effects of hormone therapy on the volume and size of the fibroids. Some studies have demonstrated an increase in size of pre-existing asymptomatic fibroids and formation of new fibroids with higher doses of progestogen in combination therapy. The finding of low resistance index in uterine arteries of women with asymptomatic fibroids is associated with an increased risk of fibroid growth, and thus making the measurement of pulsatility index of uterine arteries a possible screening tool before initiating hormone therapy in menopausal women with fibroids. Although the effect of hormone treatment is variable and statistically insignificant in many cases, the newer selective estrogen receptor modulators having tissue-specific estrogen agonistic and antagonistic actions such as raloxifene have a favorable clinical profile and may be better alternatives in women with asymptomatic fibroids.