Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
Pregnancy ; Female ; Humans ; Adult ; Hyperplasia ; Progestins ; Fertility Preservation ; Endometrial Neoplasms/pathology* ; Endometrial Hyperplasia/surgery* ; Treatment Outcome ; Precancerous Conditions ; Fertility ; Class I Phosphatidylinositol 3-Kinases ; Retrospective Studies

OBJECTIVE: To evaluate the effectiveness of oral contraceptive pill (OCP) as therapy for endometrial hyperplasia (EH) without atypia in reproductive-aged women compared with oral progestin. METHODS: A retrospective cohort study was carried out in our reproductive center. Consecutive patients diagnosed with infertility and non-atypical EH identified through electronic database who met inclusion criteria (n=309). Patients were assigned to two treatment groups: OCP (n=216) and oral progestin (n=93); clinical and reproductive outcomes were recorded. RESULTS: Reversal of EH to normal endometrium, clinical pregnancy, live birth and miscarriage rate. Women in OCP group were younger, had higher prevalence of Polycystic Ovary Syndrome and other uterine pathology and longer duration of infertility than women in progestin group. Reversal of EH was observed in 93.52% women on OCP and in 86.02% women on progestin (p=0.032; adjusted odds ratio [aOR]= 2.35; 95% confidence interval [CI]=1.06-5.21) after the initial course of treatment for 2 to 6 months. Cyclic OCP (n=184) resulted in better response to treatment compared to continuous OCP (n=32) (95.11% vs. 84.38%; p=0.039; aOR =3.60; 95% CI =1.12-11.55). Clinical pregnancy rate in OCP group was marginally higher than progestin group (87/208, 41.83% vs. 27/90, 30.00%; p=0.054). Miscarriage (25.29% vs. 29.63%; p=0.654) and live birth rate (31.25% vs. 21.11%; p=0.074) were comparable between the groups. CONCLUSION: For the first time we demonstrate that OCP is an effective therapy for non-atypical EH and is associated with higher remission rate compared with oral progestin. Reproductive outcomes are reassuring and comparable between the two groups.
Abortion, Spontaneous ; Cohort Studies ; Contraceptives, Oral, Combined ; Drug Therapy ; Endometrial Hyperplasia ; Endometrium ; Female ; Humans ; Infertility ; Live Birth ; Odds Ratio ; Pathology ; Polycystic Ovary Syndrome ; Pregnancy ; Pregnancy Rate ; Prevalence ; Progestins ; Reproductive History ; Retrospective Studies

The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.
Age Factors ; Androgens/therapeutic use* ; Antispermatogenic Agents ; Cardiovascular Diseases/epidemiology* ; Contraceptive Agents, Male/therapeutic use* ; Gonadotropins/metabolism* ; Humans ; Male ; Progestins/therapeutic use* ; Testosterone/therapeutic use*

Venous thromboembolism is well known as one of the rare but serious adverse effects of combined oral contraceptives (COCs). The COCs with third and fourth generation progestogens were found to have higher risk of venous thrombosis than those with second generation progestogens. We present a case of pulmonary embolism in a 23-year-old nulligravid woman who was using COCs containing the third generation progestogen (desogestrel). At the time of presentation of the adverse effect, she had been using the COCs for 4 months. She had no additional risk factors for thrombosis such as smoking, surgery, tumor as well as genetic factors. This case demonstrates even young women in otherwise good health may be at risk of venous thromboembolism from low-dose formulations of COCs as an over-the-counter drug. We describe this case with a brief review of literatures.
Contraceptives, Oral* ; Contraceptives, Oral, Combined ; Desogestrel* ; Female ; Humans ; Progestins ; Pulmonary Embolism* ; Risk Factors ; Smoke ; Smoking ; Thrombosis ; Venous Thromboembolism ; Venous Thrombosis ; Young Adult

Preterm birth (PTB) is defined as birth before 37 completed weeks of gestation, which occurs in approximately 10% of all pregnancies. Prior PTB history and short cervical length (CL) are the most significant predictors of PTB. Prior PTB history can increase the risk of recurrence of PTB more than two-fold in the next pregnancy. A short CL of less than 25 mm as measured by ultrasound between 16 and 24 weeks of gestation has been shown to be the most reliable predictor of an increased risk of PTB. Progesterone is one of the few proven effective methods of preventing PTB in women with a previous history of spontaneous PTB and women with a short CL. Progestins are available in natural micronized or synthetic formulations for intramuscular or vaginal (tablet or gel) administration. Several studies have reported that 17 hydroxyprogesterone caproate injection can prevent recurrent PTB in women with a previous history of PTB. Vaginal micronized natural progesterone has also been shown to be effective in preventing PTB in women with previous PTB history or with a short CL. At present, we are performing a multi-center, randomized trial in Korea (a multicenter, randomized, open-label, investigator-initiated trial of vaginal compared with intramuscular progesterone for the prevention of PTB in high-risk pregnant women: VICTORIA protocol) to compare the efficacy between vaginal progesterone and intramuscular injection of progesterone in women with a previous preterm history or short CL. This study will provide important information to both obstetricians and patients on whether a vaginal or intramuscular regimen is better for prevention of a recurrent PTB.
17-alpha-Hydroxyprogesterone ; Female ; Humans ; Injections, Intramuscular ; Korea ; Parturition ; Pregnancy ; Pregnant Women ; Premature Birth* ; Progesterone* ; Progestins ; Recurrence ; Ultrasonography ; Victoria

OBJECTIVE: The aim of this study is to assess the effectiveness of oral progestin treatment in women diagnosed with complex atypical hyperplasia (CAH) or grade 1 endometrial cancer (G1EC), who desire to preserve their fertility, as alternative treatment to a hysterectomy. METHODS: We reviewed the medical records of women younger than 45 years old that had been diagnosed with CAH or G1EC, who expressed a desire to preserve their fertility using alternative treatment at our institution. Women without evidence of myometrial invasion on pelvic magnetic resonance imaging scans were included. The study period was between 2004 and 2014. Endometrial biopsies were taken at follow-up appointments. RESULTS: We identified 31 young women with CAH or G1EC. The median age was 33 years old (range, 20 to 41), and the median period of time undertaking the treatment was 5 months (range, 1 to 12). Twenty-three patients (74.2%) achieved complete remission (CR; median time to CR was 3 months; range, 1 to 22), 16 patients (88.9%) with CAH and 7 (53.8%) with G1EC achieved CR. 6 patients (26.1%) who had achieved CR, had recurrence of the disease (median time from CR to recurrence was 12.5 months; range, 4 to 18). Eight patients (25.8%) finally underwent a hysterectomy. CONCLUSION: Oral progestin therapy is an alternative treatment for women with CAH or G1EC who desire fertility preservation. However, more prospective studies are needed for standard progestin regimen. Also, there still remains a risk of disease progression and recurrence. Therefore, close follow-up is important during treatment and after CR. In addition, a hysterectomy is recommended as a definitive treatment after completion of childbearing.
Appointments and Schedules ; Biopsy ; Disease Progression ; Endometrial Hyperplasia ; Endometrial Neoplasms* ; Female ; Fertility ; Fertility Preservation ; Follow-Up Studies ; Humans ; Hyperplasia* ; Hysterectomy ; Magnetic Resonance Imaging ; Medical Records ; Mortuary Practice ; Progestins ; Prospective Studies ; Recurrence

OBJECTIVE: To compare real-life clinical outcomes with the levonorgestrel-releasing intrauterine system (LNG-IUS) and conventional medical therapies (CMTs), including combined oral contraceptives and oral progestins in the treatment of idiopathic heavy menstrual bleeding (HMB) in South Korea. METHODS: This prospective, observational cohort study recruited a total of 647 women aged 18 to 45 years, diagnosed with HMB from 8 countries in Asia, including 209 women from South Korea (LNG-IUS, 169; CMTs, 40), who were followed up to one year. The primary outcome was cumulative continuation rate (still treated with LNG-IUS and CMTs) at 12 months. Secondary outcomes included bleeding pattern, assessment of the treatment efficacy by treating physician and safety profile. RESULTS: The continuation rate at 12 months was significantly higher with the LNG-IUS than CMTs (85.1% vs. 48.5%, respectively; P<0.0001). The 51.5% of CMTs patients discontinued treatment and 18.8% of LNG-IUS patients discontinued treatment. The most common reasons for discontinuation for CMTs were switching to another treatment and personal reasons. When compared to CMTs, the LNG-IUS offered better reduction in subjectively assessed menstrual blood loss and the number of bleeding days, tolerability and with better efficacy in HMB, as assessed by physician's final evaluation. CONCLUSION: This study provides novel information on the real-life treatment patterns of HMB in South Korea. The efficacy of CMTs was inferior compared to the LNG-IUS in the clinical outcomes measured in this study. Due to the better compliance with LNG-IUS, the cumulative continuation rate is higher than CMTs. We conclude that the LNG-IUS should be used as the first-line treatment for HMB in Korean women, in line with international guidelines.
Asia ; Asian Continental Ancestry Group* ; Cohort Studies ; Compliance ; Contraceptives, Oral, Combined ; Female ; Hemorrhage* ; Humans ; Korea ; Progestins ; Prospective Studies ; Treatment Outcome

Cancer-related anorexia-cachexia syndrome (CACS) is a hypercatabolic state, characterized by reduced appetite and weight loss due to ongoing loss of skeletal muscle mass and adipose tissue. CACS occurs mainly in patients with advanced cancer; thus, weight loss in CACS is often associated with poor prognosis and decreased survival. A large number of studies have been conducted on various pharmacologic agents for palliation of cancer-related anorexia. The purpose of this article is to review the pre-existing pharmacologic agents used for CACS and to evaluate the evidence from current studies on each pharmacologic agent. First, appetite stimulants such as corticosteroids, progestins, cyproheptadine, and cannabinoid have been shown to be beneficial by improving appetite and helping with weight changes even if they had no effect on survival rate. Several other agents with anti-inflammatory effects (e.g., eicosapentaenoic acid, thalidomide, and melatonin), prokinetic agents (e.g., metoclopramide), anabolic agents (e.g., androgens and growth hormone), antipsychotics (e.g., mirtazapine and olanzapine), and antiemetics have also been studied in patients in CACS; however further investigations would be required to confirm the beneficial effects.
Adipose Tissue ; Adrenal Cortex Hormones ; Anabolic Agents ; Androgens ; Anorexia ; Antiemetics ; Antipsychotic Agents ; Appetite ; Appetite Stimulants ; Cachexia ; Cyproheptadine ; Eicosapentaenoic Acid ; Glucocorticoids ; Humans ; Muscle, Skeletal ; Progestins ; Prognosis ; Survival Rate ; Thalidomide ; Weight Loss

Endometrial Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Precancerous Conditions ; drug therapy ; pathology ; Progestins ; therapeutic use

OBJECTIVETo approach the expressions of estrogen receptor (ER),progestogen receptor (PR),Cerb-B2,and Ki67 index in simple mucinous carcinoma of the breast and their clinical significance.

METHODSThe clinicopathological data of 72 patients with simple mucinous carcinoma of the breast who were treated in our hospital from 1997 to 2012 were retrospectively studied. Expressions of ER,PR,Cerb-B2,and Ki67 index and their relationship with clinical characteristics were analyzed.

RESULTSNine patients had lymph node metastasis. Expressions of ER,PR,and Cerb-B2 were 77.8%,69.4%,and 3.1%,respectively. The expressions of ER,PR,and Cerb-B2 showed no correlation with age,menstrual status,and axillary lymph node metastasis (P>0.05). The expression of ER was correlated with tumor diameter (P=0.008) while the expression of PR and Cerb-B2 showed no such correlation.

CONCLUSIONSHigh ER or PR expression and low Cerb-B2 expression predict good prognosis in patients with simple mucinous carcinoma of the breast. Combined detection of ER,PR,Cerb-B2,and Ki67 index may help to improve the multidisciplinary management of simple mucinous carcinoma of the breast.

Adenocarcinoma, Mucinous ; Breast Neoplasms ; Humans ; Ki-67 Antigen ; Lymphatic Metastasis ; Progestins ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Retrospective Studies