Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.

Effect of aerobic exercise on insulin resistance and centra1 adiposity disappeared after the discontinuation of intervention in overweight women

Purpose： This study aimed to assess whether the benefits of exercise on central adiposity and insulin resistance （HOMA-IR） are maintained after discontinuation of intervention in the overweight/obese （OWOB） women. Methods： The study subjects were from 2 independent studies with similar aerobic exercise （AE） intervention programs. In study I, I50WOB postmenopausal women with pre-diabetes （body mass index, BMI = 24-33 kg/m2, aged 52-65 years） completed an 8-month exercise intervention and were followed for 2 years after the intervention. In study lI, 12 OWOB （BM1 = 25-35 kg/m2, aged 30-50 years） premenopausal women participated in a 6-week AE and were followed for 4 years after the intervention. The exercise program consisted of progressive AE with intensity of 60%-75% of initial fitness level, 30-60 min/time and 3-5 times/week. Fat mass （FM） was assessed by Dual Energy X-ray Absorptiometry （DXA Prodigy; study I） or bioelectrical impedance device （Inbody 720; study II）. Plasma glucose and insulin were assessed by chemiluminescent immunoassay and HOMA-IR was calculated. Results： Both 8-month and 6-week moderate AE were effective in reducing HOMA-IR （-18.9%, p = 0.012 and -26.7%, p = 0.046, respectively）, and 8-month AE reduced FM at upper abdominal region （-6.2%, p = 0.021）. However, these improvements were not maintained in either study at the follow-up. Conclusion： The AE program used in these studies was effective to reduce insulin resistance and/or FM in central body region among overweight and obese women. However, when exercise intervention was discontinued, the beneficial effects following both short- and long-term intervention disappeared. Thus maintaining exercise seems to be required if one wants to reap the benefits of exercise in the long-term.

Nonalcoholic fatty liver disease and polycystic ovary syndrome

Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease,in patients without significant alcohol consumption.Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome(PCOS),one of the most common endocrinopathies in premenopausal women,which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome.Obesity,in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS.Moreover,existing data support that androgen excess,which is the main feature of PCOS and is interrelated to insulin resistance,may be an additional contributing factor to the development of NAFLD.Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients,limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD.PCOS patients,particularly obese patients with features of the metabolic syndrome,should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound.Lifestyle modifications including diet,weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD.When pharmacologic therapy is considered,metformin may be used,although currently there is no medical therapy of proven benefit for NAFLD.Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation,follow-up protocol and optimal treatment for PCOS patients with NAFLD.

Ovarian Thecoma Fibroma Causing Menstrual Disorder &Infertility: Dramatic Resolution with Surgery

Purpose: To report the case of successfully managed oligo-amenorrhoea with infertility as a result of thecoma fibroma in a young Nigerian Igbo woman. Case Presentation: She was a 24-year-old, married, nulliparous woman who presented with 5 years history of oligomenorrhoea and 18 months history of infertility. Following her menarche at 14 years of age, she had a regular 30-day menstrual cycle with 4 - 6 days moderate flow. Symptoms of oligomenorrhoea worsened to amenorrhoea over time with menstrual flow occurring only when a progesterone agent was used. Clinical evaluation revealed no abnormalities in the systems apart from the presence of left adnexal mass on pelvic examination. Radiological test suggested benign left adnexal mass. Results: She had surgical removal of the mass after work up. Her normal menstrual flow resumed 48 hours following surgery and became regular thereafter. The histopathology report confirmed thecoma-fibroma. She commenced sexual intercourse 12 weeks after surgery. At 18 weeks post operative period, she presented with amenorrhoea and pregnancy symptoms. Intra-uterine pregnancy was confirmed with a pelvic ultrasound scan. She was managed in antenatal clinic till 38 weeks gestational age when she had spontaneous vaginal delivery of a live female neonate that weighed 3 kg with good APGAR scores. She is currently being followed up. Conclusion: Ovarian thecoma-fibroma is a rare cause of menstrual irregularities and infertility in young women. Surgical removal could result in a dramatic and favourable clinical response, as in the case presented.

Bone Loss in Women with Type 1 Diabetes

Background: Although osteoporosis has been investigated and debated in the diabetic population over the past decades, very little is known about the spontaneous changes in bone mineral density (BMD) and biochemical markers of bone turnover in pre- and postmenopausal type 1 diabetic (T1DM) women over time. Aim: To measure spontaneous changes in BMD and biochemical markers of bone turnover in pre- and postmenopausal T1DM women. Subjects: 53 T1DM women (31 premenopausal and 22 postmenopausal) from the outpatient clinic were enrolled in the study in 1993 and 35 (22 premenopausal, 13 postmenopausal) were reexamined in 1997. Method: BMD was measured at femoral neck (f.n.), spine (L2 - L4), total body and forearm with DXA or SXA in 53 T1DM women. 4 years later a re-scan was carried out on 35 T1DM. Results: In premenopausal subjects a yearly decrease less than 1% at f.n., spine, forearm and total body was observed, though only statistically significant (s.s.) at f.n., p ≤ 0.05. In postmenopausal subjects a s.s. decrease less than 2% was observed at f.n., forearm and total body, p ≤ 0.05. In general, osteopenic or osteoporotic values were observed at the measured skeletal sites. Only at f.n. a lower s.s. BMD compared to age-matched reference women was seen. Conclusion: Small or non-significant changes in BMD and biochemical markers of bone turnover were observed in pre- and postmenopausal T1DM subjects after a 4-year period.

Yield of capsule endoscopy in obscure gastrointestinal bleeding:A comparative study between premenopausal and menopausal women

AIM To evaluate differences in capsule endoscopy(CE) performed in the setting of obscure gastrointestinal bleeding(OGIB) among premenopausal women(PMW) and menopausal women(MW).METHODS Retrospective, single-center study, including female patients submitted to CE in the setting of OGIB between May 2011 and December 2016. Patients were divided into 2 groups according to age, considering fertile age as ≤ 55 years and postmenopausal age as > 55 years. The diagnostic yield(DY), the rebleeding rate and the time to rebleed were evaluated and compared between groups. Rebleeding was defined as a drop of Hb > 2 g/dL or need for transfusional support or presence of melena/hematochezia.RESULTS A hundred and eighty three female patients underwent CE for OGIB, of whom 30.6%(n = 56) were PMW and 69.4%(n = 127) were MW. The DY was 30.4% in PMW and 63.8% in MW. The most common findings were angiodysplasias in both groups(PMW: 21.4%, MW: 44.9%)(P = 0.003). In PMW, only 1.8% required therapeutic endoscopy. In 17.3% of MW, CE findingsled to additional endoscopic treatment. Rebleeding at 1, 3 and 5 years in PMW was 3.6%, 10.2%, 10.2% and 22.0%, 32.3% and 34.2% in MW. Postmenopausal status was significantly associated with higher DY(P < 0.001), TY(P = 0.003), rebleeding(P = 0.031) and lower time to rebleed(P = 0.001).CONCLUSION PMW with suspected OGIB are less likely to have significant findings in CE. In MW DY, need for endoscopic treatment and rebleeding were significantly higher while time to rebleed was lower.

Impaired of Sexuality in Premenopausal Breast Cancer Patients

Introduction: The treatment modalities for Breast cancer may impair the sexual function of women, especially in the pre-menopausal period. Treatment in this group of women has a huge impact in quality of life. The main objective of this study was to evaluate the prevalence of sexual dysfunction (SD) after treatment for breast cancer among women who were premenopausal at the diagnosis of neoplasia. Material and Methods: All women diagnosed with premenopausal breast cancer at one outpatient clinic from March 2019 to September 2020 were selected. Participants answered two sexual function questionnaires (the Female Sexual Function Index [FSFI-19] and Female Sexual Quotient [QS-F]) and a quality of life [QOL] questionnaire [EORTC QLQ-C30]). Sociodemographic and tumor characteristics were also studied. Results: Fifty-eight pre-menopausal women were included. Sexual dysfunction (SD) was observed in 43 participants (74.1%) according to the FSFI-19, while 31 (53.4%) had SD according to the QS-F. The functional and general health scales of the EORTC QLQ-C30 were positively related to the FSFI-19 and QS-F scores, while the symptom scale was negatively related to the FSFI-19 and QS-F scores. There was no relationship between chemotherapy, hormone therapy, or surgery with the FSFI-19 and QSF scores. A diagnosis of depression was negatively related to the total FSFI-19 scores. Conclusion: Pre-menopausal breast cancer women showed high rates of female SD. None breast cancer treatment modality was related to SD. The only studied variable associated with SD was depression.

Acupoints selection pattern in acupuncture-moxibustion treatment of perimenopausal syndrome from 2007 to 2016

Objective： To discuss the acupoints selection pattern in acupuncture-moxibustion treatment of perimenopausal syndrome（PMS） from 2007 to 2016. Methods： Clinical literatures related to PMS treated with acupuncture-moxibustion published from 2007 to 2016 were collected from Chinese Biomedical Literature Database（CBM）, Chongqing VIP Database（CQVIP）, China National Knowledge Infrastructure（CNKI）, and Wanfang Academic Journal Full-text Database（Wanfang）. The retrieved data underwent descriptive analysis, cluster analysis and association pattern analysis to determine the acupoints selection principle in acupuncture-moxibustion treatment of PMS. Results： The top five acupoints used in acupuncture-moxibustion treatment of PMS were Sanyinjiao（SP 6）, Shenshu（BL 23）, Guanyuan（CV 4）, Baihui（GV 20）, and Shenmen（HT 7）. The leading 4 meridians were Bladder Meridian, Conception Vessel, Spleen Meridian, and Governor Vessel. The clustering analysis showed that the 5 core acupoint groups were：（1） Sanyinjiao（SP 6）;（2） Shenshu（BL 23） and Guanyuan（CV 4）;（3） Baihui（GV 20）, Shenmen（HT 7）, Zusanli（ST 36）, Ganshu（BL 18） and Taichong（LR 3）;（4） Taixi（KI 3）, Pishu（BL 20）, Xinshu（BL 15）, Qihai（CV 6） and Neiguan（PC 6）;（5） Sishencong（EX-HN 1）, Zhongwan（CV 12）, Hegu（LI 4）, Yintang（GV 29）, Fengchi（GB 20）, Zhongji（CV 3） and Feishu（BL 13）. The three most significant acupoints were Sanyinjiao（SP 6）, Shenshu（BL 23） and Guanyuan（CV 4）. Acupoint groups based on syndrome differentiation included：（1） Hegu（LI 4）, Zhongwan（CV 12） and Sishencong（EX-HN 1）;（2） Feishu（BL 13）, Zhongji（CV 3）, Fengchi（GB 20） and Yintang（GV 29）;（3） Xinshu（BL 15）, Pishu（BL 20）, Qihai（CV 6）, Neiguan（PC 6） and Taixi（KI 3）;（4） Ganshu（BL 18）, Zusanli（ST 36）, Shenmen（HT 7）, Taichong（LR 3） and Baihui（GV 20）. The analysis of association pattern elaborated that Shenshu（BL 23） and Sanyinjiao（SP 6） won the highest support rate in the paired groups; Ganshu（BL 18）, Shenshu（BL 23） and Sanyinjiao（SP 6） had the highest support rate among the acupoint groups. Conclusion： The data mining results of acupuncture-moxibustion treatment of PMS substantially conform to the general principle in traditional acupuncture-moxibustion theories, able to reflect the acupoints selection and grouping pattern and provide references for acupuncture-moxibustion treatment of PMS.

Clinical and angiographic characteristics of premenopausal women with coronary artery disease

Background Coronary artery disease （CAD） is generally considered as a disease of middle-aged men. It is widely accepted that the risk for CAD of premenopausal women is low because of hormone protection. Based on our clinical experience, more and more premenopausal women suffer from angina and myocardial infarction without adequate concern. Even now, there are still limited detailed data to describe the characteristics, mechanism and prognosis of premenopausal CAD patients. This article aimed to analyze the clinical and angiographic characteristics of premenopausal women with CAD. Methods A total of 565 premenopausal women and 721 postmenopausal women （56-60 years old） who underwent coronary angiography for the first time from April 2004 to December 2007 were enrolled. The clinical data and coronary angiographic characteristics （presence, localization, length and severity） were compared between the premenopausal and postmenopausal CAD groups. Results Premenopausal CAD patients presented less frequently with hypertension, diabetes mellitus and dyslipidemia compared with postmenopausal CAD patients （55.0% vs 66.0%, 15.0% vs 31.5%, 23.9% vs 37.4%, respectively; all P 〈0.05）. Although we found more frequent involvement of single vessel in premenopausal CAD （43.2% vs 26.9%, P=0）, and triple vessels in postmenopausal （56-60 years old） CAD patients （33.8% vs 20.4%, P=0）, much more severe lesions （z90%） at left main （2.9% vs 1.1%, P=0.048） and proximal left anterior descending artery （LAD） （28.2% vs 16.6%, P=0） in the premenopausal CAD group were found. Conclusion Premenopausal women with chest discomfort are always found to have obvious atherosclerosis, more .inclined to be located at the left main and proximal LAD, which is a strong predictor of an adverse clinical outcome.

Efficacy of self-made Gengnian decoction on phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin signaling pathway in perimenopausal rats

OBJECTIVE:To investigate the efficacy of self-made Gengnian decoction on expressions of phosphatidylinositol 3-kinase(PI3 K),protein kinase B(Akt)and mammalian target of rapamycin(m TOR)in ovarian tissues of perimenopausal rats.They were identified with symptom pattern of kidney-Yang deficiency in terms of Traditional Chinese Medicine.METHODS:Female Sprague-Dawley rats aged10-12 months were selected.Estrous cycle was observed by vaginal smears of keratinocytes to screen the perimenopausal model rats.The chosen rats were randomly divided into five groups,including perimenopausal model of kidney-Yang deficiency group(24 rats),self-made Gengnian decoction of high-dose group(24 rats),self-made Gengnian decoction of middle-dose group(24 rats),self-made Gengnian decoction of low dose group(24 rats)and tibolone control group(24 rats).In addition,rats aged 4-6 months were selected as young control group.The perimenopausal model rats of kidney-Yang deficiency were prepared by alternative intramuscular injection of hydrocortisone 5 mg·kg^-1·d^-1The successfully prepared models in self-made Gengnian decoction of high-dose,middle-dose and low-dose groups and tibolone control group were given self-made Gengnian decoction 26.4,13.2 and 6.6 mg·kg^-1·d^-1,and tibolone tablets solvent 0.22 mg·kg^-1·d^-1,respectively,through intragastric administration.Models group and young control group were given the same dose of normal saline,1 time a day for 15 consecutive days.24 h after the last administration,blood and ovarian tissues were collected after anesthesia with 20%ethyl carbamate.The follicles of different levels in ovarian tissue were observed and counted by histopathological hematoxylin-eosin staining.Enzyme linked immunosorbent assay was applied to test insulin-like growth factor-1(IGF-1)level in the serum of experimental rats.The expression levels of PI3 K,phosphorylated-Akt(p-Akt)and phosphorylated-m TOR(p-m TOR)m RNA in ovarian tissue were detected by quantitative real-time polymerase chain reaction.RESULTS:The total follicle counts of perimenopausal model rats with kidney-Yang deficiency were significantly reduced,and the number of follicles(mainly increased in preantral follicles and antral follicles)in perimenopausal model rats with kidney-Yang deficiency was significantly increased after intervention of high and middle doses of Gengnian decoction and tibolone(P<0.05).Compared with normal rats in young control group,the levels of IGF-1 in serum of perimenopausal rats with kidney-Yang deficiency were significantly decreased(P<0.01),and those intervened by high dose of Gengnian decoction and tibolone were significantly up-regulated.The relative expression levels of PI3 K,p-Akt,p-m TOR m RNA in ovarian tissues of perimenopausal rats with kidney-Yang deficiency were significantly lower than those of young rats(P<0.01),and those intervened by high dose of Gengnian decoction and tibolone were significantly up-regulated(P<0.05).CONCLUSION:Self-made Gengnian decoction can increase the levels of IGF-1,PI3 K,Akt and m TOR m RNA expression in serum.

Drug flibanserin–in hypoactive sexual desire disorder

Hypoactive sexual desire disorder(HSDD)is a widely known type of female sexual dysfunction that could also cause emotional distress and relationship problems.Flibanserin,a benzimidazole,was being studied as a treatment for premenopausal women with hypoactive sexual desire disorder because there was no accurate drug therapy available at the time(HSDD).The US Food and Drug Administration(FDA)approved Flibanserin in 2015 for the treatment of generalised acquired HSDD in premenopausal women.It has a high affinity for postsynaptic 5-HT-1A receptors(agonist)and 5-HT-2A receptors(antagonist),and it tends to work by increasing dopamine and noradrenaline levels in the brain while decreasing serotonin levels.This review was to assess Flibanserin efficacy and safety and it is found the drug Flibanserin benefits did not outweigh the risks in premenopausal and postmenopausal women.