Hospital-based interventional two-arm parallel comparative study on dydrogesterone vs combined oral contraceptive pills for functional ovarian cysts.

Background: Functional ovarian cysts are common among women of reproductive age, often necessitating medical intervention. This hospital-based interventional study compares the efficacy and safety of combined oral contraceptive pills (COC) and dydrogesterone in managing functional ovarian cysts. Methods: This randomized controlled trial will be conducted over two years at the Department of Obstetrics & Gynecology, AVBRH, Datta Meghe Institute of Medical Sciences. The study population consists of reproductive-age women seeking care at the outpatient unit of Obstetrics and Gynecology at AVBRH hospital. The sample size of 46 participants per group has been calculated based on a 95% confidence interval and the estimated prevalence of functional ovarian cysts. Group A will receive low-dose COC for three menstrual cycles. At the same time, Group B will be administered dydrogesterone (10 mg twice daily) for ten days during the luteal phase, repeated across three cycles. Expected outcomes: The primary outcomes include evaluating the recession of cysts within three months, monitoring alterations in menstrual patterns (frequency, regularity, duration, and volume), assessing the necessary treatment duration, and observing potential side effects (e.g., nausea, vomiting, weight gain, and acne) and complications (e.g., thromboembolism, delayed menstrual cycles post-treatment, and interactions with other drugs). Data analysis will encompass descriptive statistics, comparative tests, and regression models to assess the primary outcomes. The significance level for hypothesis testing will be 0.05 with a two-tailed approach. Registration: CTRI/2023/04/051811.

Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Morphofunctional State of the Ovaries in Rats with Experimental Model of Functional Cysts and Their Treatment with Gonadotropin-Releasing Hormone Antagonist.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly (p=0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

Effect of dienogest on serum anti-Mullerian hormone level after laparoscopic cystectomy of ovarian endometrioma.

OBJECTIVE: This comparative study aimed to evaluate the effect of postoperative dienogest treatment on serum anti-Mullerian hormone (AMH) levels in patients undergoing laparoscopic cystectomy of ovarian endometriomas. MATERIALS AND METHODS: A total of 71 patients with ovarian endometriomas treated at our department were enrolled. After surgery, 54 patients received oral dienogest 2 mg daily continuously for 6 months (dienogest group). The other 17 patients did not receive postoperative medical treatment (control group). Serum AMH levels were measured before surgery, at 3-month period after surgery, and at the end of 6-month follow-up period. Serial changes of AMH levels were compared between the two groups. RESULTS: The age, endometrioma size, and serum AMH level before surgery were comparable between the dienogest group and the control group. The AMH levels decreased significantly at 3-month period after surgery in the dienogest group (a decrease of 65.5%; p < 0.001) and the control group (a decrease of 64.8%; p = 0.018). The AMH levels increased gradually from the nadir at 3-month period after surgery and recovered partially at the end of 6-month follow-up period in both groups. There were no statistically significant differences in the rate of reduction of serum AMH levels between the two groups (p = 0.707). CONCLUSION: Laparoscopic cystectomy of ovarian endometrioma causes a significant decrease in serum AMH levels. The rates of reduction of AMH levels are similar regardless of dienogest treatment. Postoperative dienogest treatment for 6 months has no rescue effect on serum AMH levels in these patients.

Pediatric Psoriasis Associated with Van Wyk Grumbach Syndrome: A case report.

INTRODUCTION: Psoriasis is a common chronic inflammatory condition, often beginning in childhood in approximately one-third of cases. It can be associated with various other autoimmune diseases such as rheumatoid arthritis, celiac disease, and thyroid disorders. However, its co-occurrence with Van Wyk Grumbach syndrome has not been described in the pediatric population. This syndrome, resulting from untreated hypothyroidism, is characterized by early puberty and ovarian cysts. OBSERVATION: A 15-year-old adolescent with a diagnosis of psoriasis since the age of 9 presented with chronic constipation and headaches. She exhibited early puberty (menarche at 9 years) and academic regression. Clinical examination revealed growth retardation and arterial hypertension. Hormonal analyses revealed primary hypothyroidism : Free Thyroxine (FT4)=7pmol/mL(9- 20 pmol/l), Thyroid Stimulating Hormone (TSH)=200 mIU/mL( 0,4 - 5 mUI/ml.). The ultrasound and scintigraphic appearance were suggestive of thyroiditis. Additionally, she experienced menstrual irregularities and pelvic pain. Radiological exploration revealed a left ovarian cyst. The diagnosis of Van Wyk Grumbach syndrome was established due to early puberty, hypothyroidism, and polycystic ovary. Treatment with l-thyroxine led to stabilization of blood pressure and hormonal levels. Her height remained below the target adult height. CONCLUSION: Assessment of thyroid function appears necessary in pediatric patients with psoriasis. Early hormonal replacement therapy for hypothyroidism may alleviate the symptoms of Van Wyk Grumbach syndrome and mitigate its impact on stature.

[Metformin improves polycystic ovary syndrome and activates female germline stem cells in mice].

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.

Special Considerations for Women of Reproductive Age on Anticoagulation.

Anticoagulation poses unique challenges for women of reproductive age. Clinicians prescribing anticoagulants must counsel patients on issues ranging from menstruation and the possibility of developing a hemorrhagic ovarian cyst to teratogenic risks and safety with breastfeeding. Abnormal uterine bleeding affects up to 70% of young women who are treated with anticoagulation. As such, thoughtful clinical guidance is required to avoid having young women who are troubled by their menses, dose reduce, or prematurely discontinue their anticoagulation, leaving them at increased risk of recurrent thrombosis. Informed by a review of the medical literature, we present current recommendations for assisting patients requiring anticoagulation with menstrual management, prevention of hemorrhagic ovarian cysts, and avoiding unintended pregnancy. The subdermal implant may be considered a first-line option for those requiring anticoagulation, given its superior contraceptive effectiveness and ability to reliably reduce risk of hemorrhagic ovarian cysts. All progestin-only formulations-such as the subdermal implant, intrauterine device, injection, or pills-are generally preferred over combined hormonal pills, patch, or ring. Tranexamic acid, and in rare cases endometrial ablation, may also be useful in managing menorrhagia and dysmenorrhea. During pregnancy, enoxaparin remains the preferred anticoagulant and warfarin is contraindicated. Breastfeeding women may use warfarin, but direct oral anticoagulants are not recommended given their limited safety data. This practical guide for clinicians is designed to inform discussions of risks and benefits of anticoagulation therapy for women of reproductive age.

Metformin improves polycystic ovary syndrome and activates female germline stem cells in mice / 生理学报

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.

Long-Term Medical Therapy after Laparoscopic Excision of Ovarian Endometriomas: Can We Reduce and Predict the Risk of Recurrence?

OBJECTIVES: Up to 32% of women experience anatomic recurrence after conservative surgery for endometriomas, while pain recurs in 10-40% of cases. Long-term postoperative hormonal therapy is recommended to prevent disease recurrence. We evaluated the efficacy of long-term therapy with estroprogestins (EPs) or progestins (Ps) in preventing endometrioma recurrence, as identifiable cysts and subjective symptoms, after laparoscopic excision. DESIGN: This retrospective cohort study included 375 women submitted to laparoscopic endometrioma excision. Women were followed up at 6 and 12 months and then yearly after surgery. Based on postoperative medical therapy, women were divided into 4 groups: nonusers, cyclic EP users, continuous EP users, and progestogen users. Materials, Setting, Methods: Anamnestic and anthropometric characteristics were collected as well as clinical and surgical data. Gynecological examination, and transvaginal and transabdominal ultrasound scans were performed. Pain (numerical rating score >5) and endometrioma recurrence at ultrasound (ovarian cyst with typical sonographic features ≥10 mm in mean diameter) were recorded at each examination. The reoperation rate in women with recurrence was investigated. RESULTS: The median follow-up was 3.7 years with a maximum of 16.7 years. Most patients used EPs (119 cyclic and 61 continuous users), 95 used P, and 100 were nonusers. In 135 women (36%), endometriotic cyst recurrence was diagnosed, with a mean diameter of 18.7 ± 10.8 mm (range 10-55 mm). The median recurrent cyst-free time was 7.9 years (95% CI 5.8-10.8). Dysmenorrhea was the first symptom to reappear, affecting 162 patients (43.2%). Upon multivariable regression analysis, continuous users had a lower risk of relapse (OR 0.56, 95% CI 0.32-0.99), in terms of both cysts and symptom recurrence, than patients who received no medications. The reoperation rate was 16.2%. LIMITATIONS: The main limitation of this study is its retrospective design. Also, women switching therapies throughout the follow-up period were sorted into one of the study groups based on the longest treatment taken, without considering the discontinuation rates. CONCLUSIONS: Long-term EPs, administered in a continuous regimen and starting immediately after conservative surgery for endometriomas, seem to reduce the disease recurrence risk.

Treatment of ovarian endometrial cysts in the context of recurrence and fertility.

An approach to ovarian endometrial cysts has changed considerably during recent years, especially in regard to treatment of recurrent endometriosis, fertility sparing and infertility management. Surgical treatment is the primary therapeutic option. The most efficient types of treatment are radical procedures involving adhesiolysis, removal of the cyst along with its capsule and any remaining endometriotic foci. However, small asymptomatic cysts should not be treated surgically, especially in patients older than 35 years. Surgical treatment can be considered in infertile women and those who failed to get pregnant despite 1-1.5 years of trials, as well as in cases in which in vitro fertilization is not an option. Also large cysts, with more than 4 cm in diameter, should be treated surgically due to the risk of their rupture or torsion. The most efficient preventive measure for recurrent ovarian endometriosis is unilateral oophorectomy with sparing the contralateral ovary. Such a procedure should be considered in women who are no longer interested in childbearing or present with another endometriotic cyst in the same ovary. The role of pharmacotherapy is fairly limited; it should be considered in patients in whom diffuse endometriosis is associated with pain. Therapeutic agents from the following groups can be used: estrogen-progestin preparation, gestagens, including progesteronereleasing intrauterine systems and gonadotropin-releasing hormone agonists. Women with infertility should get pregnant as soon as possible, and in patients who failed to get pregnant and/or are older than 35 years, in vitro fertilization should be the treatment of choice.

Suggestive hypothesis on a case report: Patient presenting with cyclical ovarian cysts coupled to increased cholestatic enzymes.

We describe the case of a childbearing-age woman presenting with spontaneous recurrent functional ovarian cysts and, more interestingly, chronic and asymptomatic elevation of cholestatic parameters. The patient showed no history of chronic viral infections, immunological and metabolic disorders, alcohol abuse and environmental toxins exposition. Hepatic ultrasonography and cholangio-pancreatography-magnetic-resonance excluded any morphological and structural abnormalities, while liver biopsy evidenced only minimal and not specific features of inflammation. Cholestasis indices obtained prompt recovery after each cycle of synthetic hormone therapy, implanted to treat functional ovarian cysts. She has continuously experienced the off-therapy asynchronous recurrence of liver laboratory abnormalities and functional ovarian cysts. The favorable effect of the synthetic hormone therapy to obtaining a stable recovery of this unexplained long-lasting cholestatic syndrome could be likely explained by downregulation of an endogenous ovarian overproduction, although estrogen-regulated local intracellular transduction pathways cannot be excluded.

Ovarian Clear Cell Carcinoma Detected During Long-Term Management of Endometriotic Cysts in Young Patients: Possible Heterogeneity of this Tumor.

Ovarian endometriotic cysts have been identified as the possible origin of ovarian clear cell carcinoma (OCCC), so predicting or preventing future transformation is important. Early detection of clear cell carcinoma is important because it shows low sensitivity to chemotherapy and the prognosis is worse than for other histologic types. We recently treated 2 patients with OCCC. They were both young women with no family history of cancer who received long-term oral contraceptive therapy for endometriotic cysts, and the histologic diagnosis was typical clear cell carcinoma in both patients. However, in Case 1, the tumor was detected by periodic examination, tumor expression of WT1 was positive, and the stage was IA. On the other hand, Case 2 presented with fever of unknown origin, her tumor showed expression of p53, and the stage was IVB. Case 1 is alive with no evidence of disease at 38 months after surgery, while Case 2 died after 19 months despite intensive treatment. These contrasting cases suggest that we need to be aware of the risk of cancer in young women receiving long-term hormone therapy for endometriotic cysts and that OCCC may show greater heterogeneity than what has been reported previously.

Malignant Transformation of Mature Cystic Teratoma: Is Squamous Cell Carcinoma Different From the Other Types of Neoplasm?

OBJECTIVES: Malignant transformation of mature cystic teratoma (MCT) is rare. Unlike squamous cell carcinoma (SCC) in MCT, the other types of neoplasm in MCT have not been discussed in publications. We analyzed the clinical characteristics and prognosis of the other types of neoplasm (non-SCC) compared with those of SCC. METHODS: A systematic literature search of literature published from 2000 to 2017 was conducted in PubMed, Web of Science, and Scopus. We reviewed case series that included all pathological types of malignant transformation. RESULTS: A total of 155 cases from 15 case series, including our cases, were included. Of the cases, 90 (58%) were SCC and 65 (42%) were non-SCC, including adenocarcinoma, carcinoid tumor, thyroid carcinoma, sarcoma, adenosquamous carcinoma, melanoma, sebaceous carcinoma, oligodendroglioma, signet ring cell carcinoma, and transitional cell carcinoma, in descending order of frequency. The mean ages of patients with SCC and non-SCC were 50.5 and 48.9 years, respectively. The mean tumor sizes were 14.7 cm in SCC and 13.9 cm in non-SCC. Surgical approaches were similar. First-line chemotherapy for epithelial ovarian cancers was the most commonly used regimen in SCC and non-SCC. Overall survival did not differ significantly, showing better prognosis in stage I and poor prognosis in stages II, III, and IV. A difference in overall survival was observed among pathological types of non-SCC. CONCLUSIONS: Clinical characteristics and outcomes did not differ significantly between SCC and non-SCC. However, chemotherapy regimens differed to some extent, and the possibility of difference in overall survival among pathological types of non-SCC was suggested.

Successful treatment of a giant ovarian cyst by levothyroxin in a young adult woman: A case report.

Ovarian cysts are one of the most common gynecologic affections for females. The most effective therapy is surgery, but not for all conditions. An 18-year-old woman was referred to our hospital because of menstruation disorder and abdominal distension. Ultrasound and computer tomography of the abdomen revealed a giant ovarian cyst. Magnetic resonance imaging revealed profound pituitary enlargement. Laboratory studies showed severe hypothyroidism, mild anemia, hyperlipidemia, hyperprolactinemia and an elevated level of cancer antigen-125. Regression of the giant ovarian cyst and pituitary enlargement was observed after a 5-month levothyroxine replacement therapy. Thus, for patients with ovarian cysts, hypothyroidism should be taken into account. Making correct diagnosis would avoid unnecessary surgery.

Reproductive performance in dairy cows with cystic ovarian disease after single treatment with buserelin acetate or dinoprost.

The treatment of cystic ovarian disease (COD) in dairy cows is still controversial, and some researchers recommend using gonadotropin-releasing hormone (GnRH) regardless of the type of cysts. The aim of this study was to comparatively evaluate the reproductive performance of cows diagnosed with follicular or luteal cystic structures, after treatment with either buserelin acetate (GnRH agonist) or dinoprost (prostaglandin F2-alpha or PGF2α). The diagnosis was established by ultrasonographic examinations performed twice a month starting 40-45 days after calving, until the cows were diagnosed pregnant after artificial insemination. Both types of cysts were treated either with 21 µg buserelin acetate or 25 mg dinoprost, resulting in four subject groups. After treatment, the estrus rate in cows with follicular cysts treated with dinoprost (55.1%) was significantly lower (P<0.05) than in cows treated with buserelin acetate (77.5%) or in cows diagnosed with luteal cysts (77.2% for dinoprost and 72.4% for buserelin acetate). The conception rate was higher (P<0.05) in cows with follicular cysts treated with buserelin acetate (67.7%) than in those treated with dinoprost (60%) or in those with luteal cysts (56.9% for dinoprost and 47.5% for buserelin acetate). These results show that it is preferable to differentiate between the two types of ovarian cysts before treatment. Luteal cysts can be treated with either PGF2α or GnRH analogues, with better results when PGF2α is used. Contrastingly, follicular cysts are better treated with GnRH analogues. When differentiation is not possible, GnRH analogues are recommended over PGF2α.

Oral hormonal contraception in special circumstances.

BACKGROUND: Despite the general consensus that long-acting reversible contraceptives (LARCs) are the most appropriate choice of contraception for most women, there are special circumstances when the contraceptive and non-contraceptive needs of the patient are met by oral methods. OBJECTIVE: By using case histories, we seek to demonstrate the medical and practical complexities in managing contraceptive needs that may result in oral contraception being the most appropriate choice. The cases also illustrate the resources available to enable evidence-based management. DISCUSSION: Concurrent medical conditions and non-contraceptive benefits of oral contraceptive methods will see the continued use of these medications for a significant minority of women. A comprehensive knowledge of the rapidly developing evidence regarding medical eligibility and indications for usage is required. Reference to the already highly developed and easily accessible evidence bases ensures best practice for the women and families who seek advice.

Treatment of Recurrent Ovarian Cysts and Primary Infertility by Iranian Traditional Medicine: A Case Report.

Infertility is a medical and psychosocial problem with a high prevalence. There are different treatments for this problem in Iranian traditional medicine. A 28-year-old woman presented with the complaints of 4 emergency operations of the left ovarian cyst during 4 years and infertility. Diagnostic laparoscopy showed an ovarian cyst, adhesion, and endometriosis. Hysteroscopy was unremarkable. After 2 months of letrozole administration, the ovarian cyst ruptured again. Considering the failure of conventional treatments, Iranian traditional medicine products were administered to the patient. After 3 months, the patient conceived and delivered a healthy boy through normal vaginal delivery. These compounds may help with pregnancy as a uterine tonic, vitalizer, and aphrodisiac with brain and cardiac tonic properties.

Efficiency of GnRH analogues in treating large functional ovarian cysts.

AIM: The aim of this study was to determine the potential therapeutic benefit of a single administration of a GnRH analogue in pre- menopausal women presenting large functional ovarian cysts (FOCs) (diameter > five cm). MATERIALS AND METHODS: Fifty-one patients (median age 37.4 years) diagnosed with ovarian cysts, presumed benign based on transvaginal and/or transabdominal ultrasound, were divided in three study groups. Patients of group A received no medication whereas patients of groups B and C were treated with a single administration of a GnRH analogue and combined oral contraceptives, respectively. Patients were re-examined after a three-month period. Three of the 51 patients were lost in follow-up or stopped the treatment. RESULTS: Complete resolution of the ovarian cysts was observed in eight (50%), 14 (70%), and eight (67%) patients of groups A, B, and C, respectively. No side effects were observed in either of the three groups. The positive therapeutic effect in group B did not reach statistical significance compared with the two other groups (p > 0.05). CONCLUSION: Anew option of treating large FOCS through a single-dose of a GnRH analogue is proposed and should be carefully considered. Further research is needed in order to evaluate GnRH analogues as an alternative treatment.