This review article discusses evidence that luteinizing hormone (LH) plays a primary role in the development of type 2 endometrial carcinoma in elderly women. It presents several key points of evidence:
1) Endometrial carcinoma cells overexpress LH/hCG receptors compared to normal endometrial cells, and receptor expression increases with tumor stage.
2) Activation of these receptors in endometrial carcinoma cells promotes increased cell proliferation and invasion.
3) LH levels are significantly higher in post-menopausal women who develop endometrial carcinoma compared to those who do not.
4) LH acts through multiple organs like the ovaries, adrenals, adipose tissue, and pancre
The document discusses polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism in women. PCOS is characterized by oligo- and/or anovulation, clinical or biochemical signs of hyperandrogenism, and polycystic ovaries. The pathogenesis involves both genetic and environmental factors like obesity that can increase androgen production and LH levels. Diagnosis is based on meeting at least two of three criteria: irregular periods, clinical or biochemical signs of hyperandrogenism, and polycystic ovaries. Treatment focuses on weight loss, regulating menstrual cycles, reducing hirsutism, and managing related health risks like diabetes.
Prevention of Ovarian Hyperstimulation Syndrome ( OHSS )Mohammad Emam
This document discusses the prevention of ovarian hyperstimulation syndrome (OHSS) by infertility clinicians. It defines OHSS and outlines types, pathophysiology, and rationale for prevention. The objective is to highlight the clinician's role in identifying risk factors and preventing OHSS through primary, secondary, and tertiary measures. Guidelines support strategies like antagonist protocols, triggering with GnRH agonists, and vitrification to potentially achieve an "OHSS-free clinic." Current trials explore individualized stimulation protocols while future research targets OHSS mediators. The key messages are that prevention requires attention to risks before stimulation and that OHSS can now be realistically avoided through appropriate protocols.
Hypothyroidism can impact fertility through several mechanisms. It disrupts the hypothalamic-pituitary-ovarian axis, leading to issues with ovulation and corpus luteum function. The prevalence of hypothyroidism among women of reproductive age is 2-4%. Autoimmune thyroid disease is also associated with infertility, endometriosis, and polycystic ovary syndrome. Screening for thyroid function and autoimmunity should be part of an infertility workup, as treatment of hypothyroidism or autoimmune disease may improve fertility and pregnancy outcomes.
This document discusses ovulation induction using gonadotropin preparations. It outlines the different types of gonadotropins including human menopausal gonadotropins (hMG), urofollitropin, highly purified FSH, and recombinant gonadotropins. The main indications for gonadotropin use are hypogonadotropic hypogonadism, clomiphene-resistant anovulation, unexplained infertility, and elderly patients. Various protocols are described such as step-up, step-down, chronic low-dose, and fixed dose regimens. Complications include ovarian hyperstimulation syndrome. The document recommends that gonadotropins only be used by
This study investigated whether the protein Lnk is involved in insulin resistance (IR) in polycystic ovary syndrome (PCOS). The researchers found that:
1) Lnk expression was higher in ovarian tissues from PCOS patients with IR compared to tissues from normal controls and PCOS patients without IR, mainly in follicular cells.
2) Lnk bound to and inhibited the insulin receptor and its downstream signaling molecules IRS1, Akt, ERK1/2 in response to insulin stimulation.
3) Overexpression of Lnk in ovarian cells inhibited insulin signaling and increased IRS1 phosphorylation, indicating Lnk plays a role in the development of IR in PCOS by inhibiting insulin signaling in the ovaries.
Overview on recurrent pregnancy loss etiology and risk factorpharmaindexing
This document provides an overview of the etiology and risk factors of recurrent pregnancy loss (RPL), which is defined as two or more consecutive spontaneous abortions before 20 weeks of gestation. It discusses several potential causes of RPL including genetic factors, anatomic abnormalities, endocrine factors, infectious agents, thrombotic factors, immunological issues, and unexplained etiologies. Around 50-70% of RPL cases have no identifiable cause. Advanced maternal age, paternal age, smoking, obesity, and lifestyle factors can increase the risk of RPL. Understanding the causes and risks of RPL helps to determine the best diagnostic tests and treatments.
MALE INFERTILITY Disorder of male sexual function ANILKUMAR BR
This document defines infertility as the inability to conceive after one year of unprotected intercourse. It can be primary or secondary infertility. Male infertility is often caused by issues with the hypothalamic-pituitary system, testes, or ejaculatory system. Testing includes semen analysis, hormone levels, and identifying risk factors like varicocele, infections, medications, lifestyle, and idiopathic causes. Treatment involves medications, lifestyle changes, assisted reproduction, and addressing the significant emotional burden of infertility.
The document discusses polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism in women. PCOS is characterized by oligo- and/or anovulation, clinical or biochemical signs of hyperandrogenism, and polycystic ovaries. The pathogenesis involves both genetic and environmental factors like obesity that can increase androgen production and LH levels. Diagnosis is based on meeting at least two of three criteria: irregular periods, clinical or biochemical signs of hyperandrogenism, and polycystic ovaries. Treatment focuses on weight loss, regulating menstrual cycles, reducing hirsutism, and managing related health risks like diabetes.
Prevention of Ovarian Hyperstimulation Syndrome ( OHSS )Mohammad Emam
This document discusses the prevention of ovarian hyperstimulation syndrome (OHSS) by infertility clinicians. It defines OHSS and outlines types, pathophysiology, and rationale for prevention. The objective is to highlight the clinician's role in identifying risk factors and preventing OHSS through primary, secondary, and tertiary measures. Guidelines support strategies like antagonist protocols, triggering with GnRH agonists, and vitrification to potentially achieve an "OHSS-free clinic." Current trials explore individualized stimulation protocols while future research targets OHSS mediators. The key messages are that prevention requires attention to risks before stimulation and that OHSS can now be realistically avoided through appropriate protocols.
Hypothyroidism can impact fertility through several mechanisms. It disrupts the hypothalamic-pituitary-ovarian axis, leading to issues with ovulation and corpus luteum function. The prevalence of hypothyroidism among women of reproductive age is 2-4%. Autoimmune thyroid disease is also associated with infertility, endometriosis, and polycystic ovary syndrome. Screening for thyroid function and autoimmunity should be part of an infertility workup, as treatment of hypothyroidism or autoimmune disease may improve fertility and pregnancy outcomes.
This document discusses ovulation induction using gonadotropin preparations. It outlines the different types of gonadotropins including human menopausal gonadotropins (hMG), urofollitropin, highly purified FSH, and recombinant gonadotropins. The main indications for gonadotropin use are hypogonadotropic hypogonadism, clomiphene-resistant anovulation, unexplained infertility, and elderly patients. Various protocols are described such as step-up, step-down, chronic low-dose, and fixed dose regimens. Complications include ovarian hyperstimulation syndrome. The document recommends that gonadotropins only be used by
This study investigated whether the protein Lnk is involved in insulin resistance (IR) in polycystic ovary syndrome (PCOS). The researchers found that:
1) Lnk expression was higher in ovarian tissues from PCOS patients with IR compared to tissues from normal controls and PCOS patients without IR, mainly in follicular cells.
2) Lnk bound to and inhibited the insulin receptor and its downstream signaling molecules IRS1, Akt, ERK1/2 in response to insulin stimulation.
3) Overexpression of Lnk in ovarian cells inhibited insulin signaling and increased IRS1 phosphorylation, indicating Lnk plays a role in the development of IR in PCOS by inhibiting insulin signaling in the ovaries.
Overview on recurrent pregnancy loss etiology and risk factorpharmaindexing
This document provides an overview of the etiology and risk factors of recurrent pregnancy loss (RPL), which is defined as two or more consecutive spontaneous abortions before 20 weeks of gestation. It discusses several potential causes of RPL including genetic factors, anatomic abnormalities, endocrine factors, infectious agents, thrombotic factors, immunological issues, and unexplained etiologies. Around 50-70% of RPL cases have no identifiable cause. Advanced maternal age, paternal age, smoking, obesity, and lifestyle factors can increase the risk of RPL. Understanding the causes and risks of RPL helps to determine the best diagnostic tests and treatments.
MALE INFERTILITY Disorder of male sexual function ANILKUMAR BR
This document defines infertility as the inability to conceive after one year of unprotected intercourse. It can be primary or secondary infertility. Male infertility is often caused by issues with the hypothalamic-pituitary system, testes, or ejaculatory system. Testing includes semen analysis, hormone levels, and identifying risk factors like varicocele, infections, medications, lifestyle, and idiopathic causes. Treatment involves medications, lifestyle changes, assisted reproduction, and addressing the significant emotional burden of infertility.
Newlife India has done research on Genetics of ovarian failure. Maire Peter has done the research on the same. By virtue of the extenssive reasearch we are able to give best results on IVF treatments.
This document defines premature ovarian failure as the loss of normal ovarian function before age 40, affecting 1% of women. It can be caused by genetic disorders, autoimmune diseases, chemotherapy/radiation, or unknown factors. Symptoms include irregular periods, hot flashes, and fertility issues. The condition is diagnosed through blood tests of follicle-stimulating hormone and estradiol levels. Treatment focuses on hormone replacement therapy and calcium/vitamin D supplements to prevent osteoporosis and relieve symptoms.
This document discusses infertility, its causes and treatments including assisted reproductive technologies. It notes that infertility has risen 50% in India over recent decades with 46% of Indians aged 31-40 requiring medical help to conceive. Both male and female factors contribute nearly equally to infertility. After evaluating causes for each couple, treatments may include ovulation induction, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection or use of donor gametes. New assisted reproduction techniques have increased options but the best treatment depends on the individual infertility factors involved.
Premature ovarian failure (POF) is characterized by the premature depletion of ovarian follicles before age 40, causing infertility. It is defined as elevated follicle-stimulating hormone levels above 20-40 mIU/mL before age 40 along with irregular or no menstrual periods. POF affects 1-3% of women and has various potential causes including genetic factors, autoimmune disorders, environmental exposures, infections, or idiopathic origins. Diagnosis involves hormone testing and treatment focuses on hormone replacement therapy to manage symptoms while fertility options may include oocyte donation or surrogacy.
Premature menopause is defined as secondary amenorrhea for at least 3 months with raised FSH levels and low estrogen in a woman under 40 years old. It can be caused by genetic disorders, autoimmune diseases, smoking, radiation, chemotherapy or surgery. Late menopause is menstruation continuing past 52 years and may be due to conditions like fibroids or diabetes. Benefits include delayed aging and reduced risks of osteoporosis and cardiovascular disease, while risks include increased chances of breast, uterine and ovarian cancers. Diagnosis involves cessation of periods, symptoms, and testing of vaginal cytology, estradiol, and FSH and LH levels. Management focuses on counseling, lifestyle changes, medications
Dr. Indira Devi Ponugoti is a physician who specializes in obstetrics and gynecology. She has held several prestigious positions including professor, department head, and president of various medical organizations. Her qualifications include degrees from Osmania University and she is a life member of several professional societies. Currently she serves on the state council of the Indian Medical Association in Hyderabad and is organizing committee chair for a conference.
Cushing's syndrome is caused by prolonged exposure to high levels of the hormone cortisol and can affect anyone, though it is rare. It is characterized by upper body obesity, easy bruising, high blood pressure, and other symptoms. Treatments depend on the underlying cause but may include surgery, radiation, chemotherapy, or drugs that inhibit cortisol production such as Korlym. Left untreated, Cushing's syndrome can be lethal.
The document discusses menopause and hormone replacement therapy. It defines menopause and describes the hormonal changes that occur during the menopausal transition as ovarian follicles are depleted and estrogen levels decline. This leads to symptoms like hot flashes, mood changes, and effects on the brain, skin and bones. Diagnosis of menopause is confirmed after 12 months of amenorrhea when FSH and estradiol levels indicate ovarian failure. Management of menopausal symptoms includes lifestyle changes, medications like estrogen therapy, and alternative therapies.
Genetic factors can significantly impact fertility in some individuals. These include both chromosomal abnormalities and inherited genetic diseases. Chromosomal abnormalities involve mutations that make it difficult to carry a child to term, and are sometimes caused by advanced maternal age. Inherited genetic diseases revolve around mutations in single genes that can cause serious problems in development. While physicians have limited ability to address genetic issues directly, options like preimplantation genetic diagnosis and in vitro fertilization with donor gametes can help people with genetic risks conceive safely.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition caused by fertility treatments. It can range from mild to life-threatening. Steps to prevent OHSS include identifying at-risk patients, using low gonadotropin doses, coasting by withholding gonadotropins to lower estrogen levels safely, using GnRH antagonists, and administering metformin. If OHSS occurs, management focuses on investigations, fluid monitoring, and paracentesis if needed.
The document discusses delayed puberty, defined as the absence or incomplete development of secondary sex characteristics past a certain age. It then focuses on hypogonadotrophic hypogonadism, which affects about 1 in 10,000 male births and can be associated with loss of smell. Sixteen gene defects have been linked to Kallmann syndrome. Short term goals of treatment include attaining appropriate sexual development and growth, while long term goals include maintaining normal hormone levels and inducing fertility. Pretreatment with FSH before GnRH therapy has shown promise in inducing testicular growth and fertility in men with congenital hypogonadotropic hypogonadism and underdeveloped testes.
This document summarizes research into why gestational trophoblastic neoplasms overproduce human chorionic gonadotropin (hCG). It finds that these tumors contain higher levels of hCG/LH receptors than normal placenta, preventing hCG from regulating its own biosynthesis through negative feedback. As a result, hCG levels in these tumors can increase unabated. The document also finds that inhibiting hCG production in choriocarcinoma cells leads to increased apoptosis and reduced tumor formation, showing that hCG promotes tumor survival, growth and invasion. Therefore, overproduction of hCG provides gestational trophoblastic neoplasms a strong survival and growth advantage.
Hypogonadotrophic Hypogonadism
its congenital disease, failure of communication between the hypothalamus and the anterior pituitary gland.
symptom of an altered sense of smell either completely absent (anosmia) or highly reduced (hyposmia).
for diagnosis wait and see" approach applied
Obesity negatively impacts male fertility through three main mechanisms: increased oxidative stress, hormonal imbalance and hypogonadism, and accumulation of endocrine disruptors. Weight loss through diet and exercise has been shown to improve semen quality and total sperm count. Medications that target hormonal issues like aromatase inhibitors can also help increase sperm count and function. While bariatric surgery results are mixed, assisted reproduction techniques may be needed for severely obese men to conceive.
Prevalence of infertility gravitates to increase due to different factors. Causes of male infertility could be varicocele, idiopathic infertility, testicular insufficiency, obstruction, ejaculation disorder, medicineradiation effect, undescended testis, immunological mechanisms, endocrine dysfunction such as diabetes, excessive taking of alcohol, smoking and environmental toxins such as pesticides, mercury and lead. It is furthermore understood that person, obesity, be deficient in of nutrition and habits of utilizing time for example too much use of, laptop, mobile phones, computers and sauna, etc., as for women, age, smoking, too much consumption of alcohol, having a skinny or overweight body and having been exposed to physical or mental stress fruition in amenorrhea might be the causes of infertility. The progress in infertility prevalence draws attention to the effects of factors such as lifestyle, dietetic habits and environmental factors. Male infertility originates from mostly as a result of the association between oxidative stress and antioxidants. A review of these areas will provide researchers with a more noteworthy understanding of the compulsory participation of these nutrients in male reproductive processes. This review also caustic out gaps in recent studies which will require further investigations.
Keywords: Nutrition; spermatogenesis, oligospermia, infertility, antioxidants, reproductive
This document provides information on menopause, including its definition, causes, symptoms, effects, diagnosis, and treatment options. It can be summarized as follows:
1. Menopause is defined as the permanent cessation of menstruation resulting from loss of ovarian follicles, with an average age of onset being 51 years. It can occur prematurely before age 45 due to various causes.
2. Short term symptoms include hot flashes, mood swings, sleep problems, and vaginal dryness. Long term risks include osteoporosis and increased risk of heart disease.
3. Diagnosis is based on cessation of periods for 12 months and elevated FSH levels. Treatment options include hormone
This document summarizes information about premature ovarian failure (POF). It defines POF as amenorrhea, hypoestrogenism, and elevated gonadotropins in women under age 40. POF prevalence is 1-4% under age 40, increasing to 1% by age 30 and 4% by age 40. Causes include genetic factors, autoimmunity, environmental exposures, infections, and iatrogenic factors. Symptoms include menopausal symptoms and long term risks of osteoporosis and cardiovascular disease. Diagnosis involves lab tests of hormones and imaging. Treatment is hormone replacement therapy. Annual follow up is needed to monitor treatment and screen for other related conditions.
SHREE SIDDHI SOFT SOLUTIONS research team will guide you to publish your paper in any International Conference or International Journal.
We have successfully published M.E/M.TECH.,B.E.,B.TECH.,M.PHIL, PH.D. papers in many International Journals and Conferences
Contact US:
SHREE SIDDHI SOFT SOLUTIONS
#3, 4th FLOOR, LAKSHMI ARCADE,
11TH CROSS, THILLAI NAGAR,
TRICHY-620018.
Phone NO : +91 90032-44446,900323336,0431-4040672
Email : shreesiddhisoftsolutionstrichy@gmail.com
Website : www.shreesiddhisoftsolutions.com, www.siddhisoftsolutions.com
Software & Embedded IEEE Projects for Final Year students in the best Project Centre & Software Company in trichy for Engineering (CSE, IT, ECE, EEE) & MCA Students
Contact US:
SHREE SIDDHI SOFT SOLUTIONS
#3, 4th FLOOR, LAKSHMI ARCADE,
11TH CROSS, THILLAI NAGAR,
TRICHY-620018.
Phone NO : +91 90032-44446,900323336,0431-4040672
Email : shreesiddhisoftsolutionstrichy@gmail.com
Website : www.shreesiddhisoftsolutions.com, www.siddhisoftsolutions.com
SHREE SIDDHI SOFT SOLUTIONS provides total software solutions to its customers. Apsys works closely with the customers to identify their business processes for computerization and help them implement state-of-the-art solutions. By identifying and enhancing their processes through information technology solutions. SHREE SIDDHI SOFT SOLUTIONS help it customers optimally use their resources. The latest tools are identified and customized systems are built to provide the solutions that not only address the current needs of the customers but also take care of future expansions. All Course Structures and practical’s are created by Experienced Industry Professionals. Keeping the current industry requirement and standard in mind. In a way that is easy for the students.
Contact US:
SHREE SIDDHI SOFT SOLUTIONS
#3, 4th FLOOR, LAKSHMI ARCADE,
11TH CROSS, THILLAI NAGAR,
TRICHY-620018.
Phone NO : +91 90032-44446,900323336,0431-4040672
Email : shreesiddhisoftsolutionstrichy@gmail.com
Website : www.shreesiddhisoftsolutions.com
Newlife India has done research on Genetics of ovarian failure. Maire Peter has done the research on the same. By virtue of the extenssive reasearch we are able to give best results on IVF treatments.
This document defines premature ovarian failure as the loss of normal ovarian function before age 40, affecting 1% of women. It can be caused by genetic disorders, autoimmune diseases, chemotherapy/radiation, or unknown factors. Symptoms include irregular periods, hot flashes, and fertility issues. The condition is diagnosed through blood tests of follicle-stimulating hormone and estradiol levels. Treatment focuses on hormone replacement therapy and calcium/vitamin D supplements to prevent osteoporosis and relieve symptoms.
This document discusses infertility, its causes and treatments including assisted reproductive technologies. It notes that infertility has risen 50% in India over recent decades with 46% of Indians aged 31-40 requiring medical help to conceive. Both male and female factors contribute nearly equally to infertility. After evaluating causes for each couple, treatments may include ovulation induction, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection or use of donor gametes. New assisted reproduction techniques have increased options but the best treatment depends on the individual infertility factors involved.
Premature ovarian failure (POF) is characterized by the premature depletion of ovarian follicles before age 40, causing infertility. It is defined as elevated follicle-stimulating hormone levels above 20-40 mIU/mL before age 40 along with irregular or no menstrual periods. POF affects 1-3% of women and has various potential causes including genetic factors, autoimmune disorders, environmental exposures, infections, or idiopathic origins. Diagnosis involves hormone testing and treatment focuses on hormone replacement therapy to manage symptoms while fertility options may include oocyte donation or surrogacy.
Premature menopause is defined as secondary amenorrhea for at least 3 months with raised FSH levels and low estrogen in a woman under 40 years old. It can be caused by genetic disorders, autoimmune diseases, smoking, radiation, chemotherapy or surgery. Late menopause is menstruation continuing past 52 years and may be due to conditions like fibroids or diabetes. Benefits include delayed aging and reduced risks of osteoporosis and cardiovascular disease, while risks include increased chances of breast, uterine and ovarian cancers. Diagnosis involves cessation of periods, symptoms, and testing of vaginal cytology, estradiol, and FSH and LH levels. Management focuses on counseling, lifestyle changes, medications
Dr. Indira Devi Ponugoti is a physician who specializes in obstetrics and gynecology. She has held several prestigious positions including professor, department head, and president of various medical organizations. Her qualifications include degrees from Osmania University and she is a life member of several professional societies. Currently she serves on the state council of the Indian Medical Association in Hyderabad and is organizing committee chair for a conference.
Cushing's syndrome is caused by prolonged exposure to high levels of the hormone cortisol and can affect anyone, though it is rare. It is characterized by upper body obesity, easy bruising, high blood pressure, and other symptoms. Treatments depend on the underlying cause but may include surgery, radiation, chemotherapy, or drugs that inhibit cortisol production such as Korlym. Left untreated, Cushing's syndrome can be lethal.
The document discusses menopause and hormone replacement therapy. It defines menopause and describes the hormonal changes that occur during the menopausal transition as ovarian follicles are depleted and estrogen levels decline. This leads to symptoms like hot flashes, mood changes, and effects on the brain, skin and bones. Diagnosis of menopause is confirmed after 12 months of amenorrhea when FSH and estradiol levels indicate ovarian failure. Management of menopausal symptoms includes lifestyle changes, medications like estrogen therapy, and alternative therapies.
Genetic factors can significantly impact fertility in some individuals. These include both chromosomal abnormalities and inherited genetic diseases. Chromosomal abnormalities involve mutations that make it difficult to carry a child to term, and are sometimes caused by advanced maternal age. Inherited genetic diseases revolve around mutations in single genes that can cause serious problems in development. While physicians have limited ability to address genetic issues directly, options like preimplantation genetic diagnosis and in vitro fertilization with donor gametes can help people with genetic risks conceive safely.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition caused by fertility treatments. It can range from mild to life-threatening. Steps to prevent OHSS include identifying at-risk patients, using low gonadotropin doses, coasting by withholding gonadotropins to lower estrogen levels safely, using GnRH antagonists, and administering metformin. If OHSS occurs, management focuses on investigations, fluid monitoring, and paracentesis if needed.
The document discusses delayed puberty, defined as the absence or incomplete development of secondary sex characteristics past a certain age. It then focuses on hypogonadotrophic hypogonadism, which affects about 1 in 10,000 male births and can be associated with loss of smell. Sixteen gene defects have been linked to Kallmann syndrome. Short term goals of treatment include attaining appropriate sexual development and growth, while long term goals include maintaining normal hormone levels and inducing fertility. Pretreatment with FSH before GnRH therapy has shown promise in inducing testicular growth and fertility in men with congenital hypogonadotropic hypogonadism and underdeveloped testes.
This document summarizes research into why gestational trophoblastic neoplasms overproduce human chorionic gonadotropin (hCG). It finds that these tumors contain higher levels of hCG/LH receptors than normal placenta, preventing hCG from regulating its own biosynthesis through negative feedback. As a result, hCG levels in these tumors can increase unabated. The document also finds that inhibiting hCG production in choriocarcinoma cells leads to increased apoptosis and reduced tumor formation, showing that hCG promotes tumor survival, growth and invasion. Therefore, overproduction of hCG provides gestational trophoblastic neoplasms a strong survival and growth advantage.
Hypogonadotrophic Hypogonadism
its congenital disease, failure of communication between the hypothalamus and the anterior pituitary gland.
symptom of an altered sense of smell either completely absent (anosmia) or highly reduced (hyposmia).
for diagnosis wait and see" approach applied
Obesity negatively impacts male fertility through three main mechanisms: increased oxidative stress, hormonal imbalance and hypogonadism, and accumulation of endocrine disruptors. Weight loss through diet and exercise has been shown to improve semen quality and total sperm count. Medications that target hormonal issues like aromatase inhibitors can also help increase sperm count and function. While bariatric surgery results are mixed, assisted reproduction techniques may be needed for severely obese men to conceive.
Prevalence of infertility gravitates to increase due to different factors. Causes of male infertility could be varicocele, idiopathic infertility, testicular insufficiency, obstruction, ejaculation disorder, medicineradiation effect, undescended testis, immunological mechanisms, endocrine dysfunction such as diabetes, excessive taking of alcohol, smoking and environmental toxins such as pesticides, mercury and lead. It is furthermore understood that person, obesity, be deficient in of nutrition and habits of utilizing time for example too much use of, laptop, mobile phones, computers and sauna, etc., as for women, age, smoking, too much consumption of alcohol, having a skinny or overweight body and having been exposed to physical or mental stress fruition in amenorrhea might be the causes of infertility. The progress in infertility prevalence draws attention to the effects of factors such as lifestyle, dietetic habits and environmental factors. Male infertility originates from mostly as a result of the association between oxidative stress and antioxidants. A review of these areas will provide researchers with a more noteworthy understanding of the compulsory participation of these nutrients in male reproductive processes. This review also caustic out gaps in recent studies which will require further investigations.
Keywords: Nutrition; spermatogenesis, oligospermia, infertility, antioxidants, reproductive
This document provides information on menopause, including its definition, causes, symptoms, effects, diagnosis, and treatment options. It can be summarized as follows:
1. Menopause is defined as the permanent cessation of menstruation resulting from loss of ovarian follicles, with an average age of onset being 51 years. It can occur prematurely before age 45 due to various causes.
2. Short term symptoms include hot flashes, mood swings, sleep problems, and vaginal dryness. Long term risks include osteoporosis and increased risk of heart disease.
3. Diagnosis is based on cessation of periods for 12 months and elevated FSH levels. Treatment options include hormone
This document summarizes information about premature ovarian failure (POF). It defines POF as amenorrhea, hypoestrogenism, and elevated gonadotropins in women under age 40. POF prevalence is 1-4% under age 40, increasing to 1% by age 30 and 4% by age 40. Causes include genetic factors, autoimmunity, environmental exposures, infections, and iatrogenic factors. Symptoms include menopausal symptoms and long term risks of osteoporosis and cardiovascular disease. Diagnosis involves lab tests of hormones and imaging. Treatment is hormone replacement therapy. Annual follow up is needed to monitor treatment and screen for other related conditions.
SHREE SIDDHI SOFT SOLUTIONS research team will guide you to publish your paper in any International Conference or International Journal.
We have successfully published M.E/M.TECH.,B.E.,B.TECH.,M.PHIL, PH.D. papers in many International Journals and Conferences
Contact US:
SHREE SIDDHI SOFT SOLUTIONS
#3, 4th FLOOR, LAKSHMI ARCADE,
11TH CROSS, THILLAI NAGAR,
TRICHY-620018.
Phone NO : +91 90032-44446,900323336,0431-4040672
Email : shreesiddhisoftsolutionstrichy@gmail.com
Website : www.shreesiddhisoftsolutions.com, www.siddhisoftsolutions.com
Software & Embedded IEEE Projects for Final Year students in the best Project Centre & Software Company in trichy for Engineering (CSE, IT, ECE, EEE) & MCA Students
Contact US:
SHREE SIDDHI SOFT SOLUTIONS
#3, 4th FLOOR, LAKSHMI ARCADE,
11TH CROSS, THILLAI NAGAR,
TRICHY-620018.
Phone NO : +91 90032-44446,900323336,0431-4040672
Email : shreesiddhisoftsolutionstrichy@gmail.com
Website : www.shreesiddhisoftsolutions.com, www.siddhisoftsolutions.com
SHREE SIDDHI SOFT SOLUTIONS provides total software solutions to its customers. Apsys works closely with the customers to identify their business processes for computerization and help them implement state-of-the-art solutions. By identifying and enhancing their processes through information technology solutions. SHREE SIDDHI SOFT SOLUTIONS help it customers optimally use their resources. The latest tools are identified and customized systems are built to provide the solutions that not only address the current needs of the customers but also take care of future expansions. All Course Structures and practical’s are created by Experienced Industry Professionals. Keeping the current industry requirement and standard in mind. In a way that is easy for the students.
Contact US:
SHREE SIDDHI SOFT SOLUTIONS
#3, 4th FLOOR, LAKSHMI ARCADE,
11TH CROSS, THILLAI NAGAR,
TRICHY-620018.
Phone NO : +91 90032-44446,900323336,0431-4040672
Email : shreesiddhisoftsolutionstrichy@gmail.com
Website : www.shreesiddhisoftsolutions.com
Este documento describe varios tipos de periféricos de almacenamiento, incluyendo discos flexibles, discos duros, cintas magnéticas, DVD, tarjetas de memoria USB y lectores de tarjetas. Explica que los periféricos de almacenamiento permiten guardar y recuperar información y varían en velocidad, fiabilidad, costo, tamaño y capacidad de almacenamiento. También cubre brevemente periféricos de multimedia como tarjetas de sonido, bafles y micrófonos.
The feeding biomechanics and dietary ecology of australopithecus africanus (s...Kristian Pedersen
1) The feeding biomechanics and craniofacial morphology of Australopithecus africanus were analyzed using finite element analysis informed by comparative data.
2) The results suggest that the facial skeleton of A. africanus was well-adapted to withstand loads applied during premolar biting, including stresses along the nasal margins and zygomatic root.
3) However, neither the mastication of small hard objects nor large volumes of food alone can fully explain the evolution of the robust facial features in A. africanus. Rather, key aspects are more likely related to ingesting and processing large mechanically protected foods like nuts and seeds.
El documento presenta las cualidades y habilidades necesarias para el emprendimiento como el esfuerzo, la resiliencia, la determinación, la pasión, la capacidad de adaptación, la innovación, la paciencia, la creatividad, la autonomía, la confianza en sí mismo, la tenacidad, el liderazgo, el espíritu de equipo, la solidaridad, la capacidad de redactar, la comunicación oral y la resolución. Además, explica brevemente cada una de estas características.
El documento habla sobre el mantenimiento preventivo de sistemas. Detalla los nombres de tres estudiantes, la modalidad y materia a la que pertenecen. El propósito de un mantenimiento es mejorar el funcionamiento del equipo.
Los virus informáticos son programas maliciosos que se propagan a través de software y pueden dañar sistemas. Existen varios tipos como troyanos, gusanos y bombas lógicas. Los antivirus detectan y eliminan virus mediante firmas, heurística y planificación. Es importante usar software actualizado y evitar enlaces sospechosos para protegerse de virus.
Este documento describe varios tipos de periféricos de almacenamiento, incluyendo discos flexibles, discos duros, cintas magnéticas, DVD, tarjetas de memoria USB y lectores de tarjetas. Explica que los periféricos de almacenamiento permiten guardar y recuperar información y varían en velocidad, fiabilidad, costo, tamaño y capacidad de almacenamiento. También cubre brevemente periféricos de multimedia como tarjetas de sonido, bafles y micrófonos.
This document contains details of various cloud computing, data mining, mobile computing, network/network security, information forensics, and image processing research projects and application projects conducted by Shree Siddhi Soft Solutions. It includes the titles, IDs, and years of over 100 projects. The projects cover topics such as cloud federations, data storage and processing in mobile cloud, attribute-based access control, trajectory pattern mining, malware detection, localization in underwater acoustic networks, and more. It also lists application projects in various domains like healthcare, travel, and education.
Tipos de software para quemar dvd santiago-restrepo-10-8Restrepo1912
El documento describe 6 programas populares para grabar DVD: BurnAware, CDBurnerXP, ImgBurn, Ashampoo Burning Studio Free, InfraRecorder y Free Any Burn. Cada programa ofrece funciones básicas como grabar archivos y copiar discos, pero algunos también incluyen funciones avanzadas como extraer pistas de audio o convertir formatos de archivo.
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3. The role of follicle stimulating hormone is unknown, but evidence suggests luteinizing hormone may be involved in the development of endometrial carcinomas in elderly women through elevated levels causing hyperactivity of the hypothalamic-pituitary axis.
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This document provides an overview of the clinical presentation and diagnosis of polycystic ovarian syndrome (PCOS). PCOS is a common endocrinopathy in reproductive-aged women, characterized by menstrual irregularities, infertility, hirsutism and obesity. The exact causes are unknown but involve abnormalities in gonadotropin secretion and ovarian function. Diagnosis requires two of three criteria - oligo/anovulation, clinical or biochemical signs of hyperandrogenism, and polycystic ovaries. PCOS presents challenges to diagnose in adolescents and perimenopausal women due to normal hormonal fluctuations during these stages of life.
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A Case Report on Intrahepatic Cholestasis of Pregnancyijtsrd
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Overview on Recurrence Pregnancy Loss etiology and risk factorspharmaindexing
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2) Animal studies show that hCG treatment mimics the benefits of pregnancy for RA and SS, reducing inflammation and immune responses.
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C.V. Rao is a professor at Florida International University's Herbert Wertheim College of Medicine in Miami, Florida. He has over 45 years of research experience and his research interests include the non-gonadal actions of human chorionic gonadotropin and luteinizing hormone. He has published over 260 peer-reviewed journal articles, 40 book chapters, and 380 scientific abstracts.
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Human chorionic gonadotropin (hCG) is best known as the hormone detected in pregnancy tests, but it has many other roles and functions beyond early pregnancy. While hCG was long thought to only function in supporting the corpus luteum during pregnancy, research over the past 20 years has shown that hCG regulates numerous non-gonadal tissues through its receptors. These regulatory roles include supporting fetal growth and development, safeguarding the fetus from rejection, and allowing delivery when the fetus is mature. The broad regulatory roles of hCG are not entirely unexpected, as many other hormones also have multiple sites of action beyond their main targets. The evolution of these multiple hormone functions is thought to provide functional redundancy and efficiency in response
1. Review article
Luteinizing hormone is a primary culprit in the endometrial carcinoma
development in elderly women
C.V. Rao *
Departments of Cellular Biology and Pharmacology, Molecular and Human Genetics and Obstetrics and Gynecology, Reproduction and Development Program,
Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
1. Introduction
ECs are the most common gynecologic malignancies with a
higher incidence than ovarian and cervical cancers in Western
countries.1–3
Greater than 95% of endometrial carcinomas are
adenocarcinomas.1–3
The incidence increases with age, thus, 80% of
ECs are seen among post-menopausal women.1–3
Caucasian
women are at a greater risk than black, Hispanic, Asian and Pacific
Islanders, but black women are most likely to die from the
disease.4,5
The incidence of EC is on the rise without an increase in
survival rates during the last four decades.4–6
According to some
estimates, there were about 55,000 new cases and 10,000 died
from EC in 2015.4,5
The estimated economic impact of this
malignancy is about $2.6 billion per year.6
EC is a story of two diseases.7,8
While type 1 disease is
diagnosed in pre-menopausal women, type 2 disease primarily
occurs among post-menopausal women.7,8
The tumors from Type
1 disease are of endometriod histology, usually stages 1 or 2 and
have a favorable prognosis. The tumors from type 2 diseases, on the
other hand, have non-endometrial histology, including serous,
clear cell, mucinous and other high-grade tumors. Type 1 disease is
not usually aggressive, well differentiated, estrogen dependent,
contain estrogen, and progesterone receptors (ER and PR), slow to
spread and can be successfully treated with surgery or with
progestins.7,8
Type 2 disease, on the other hand, is aggressive,
poorly differentiated, estrogen independent, do not contain ER or
PR, vascular, spreads outside the uterus and has a poor prognosis
that requires aggressive treatment.7,8
Type 2 ECs show aneuploidy,
p53
mutations, alterations in several genes, including those
involved in cell cycle progression.9–15
Age, obesity, diabetes, reproductive and family history are some
of the risk factors for type 2 EC development.4,5,16–20
The risk is
modulated by the degree of obesity, thus body mass index has a
strong association with an increased risk.4,5,16–20
Type 2 ECs are associated with bleeding and also pelvic pain and
pressure.4,5
Definitive diagnosis is made by endometrial biopsy or
may be suspected by transvaginal ultrasound and then confirmed
by biopsy.4,5
ECs are surgically staged tumors.21
The early stages
(stages I/II) are usually curable with an excellent 5 year survival
rates.21
Stage IV disease, on the other hand, has less than 10%
survival rates at 5 years.21
Based on the scientific data, we suggest
that LH is a culprit in the type 2 EC development in elderly women.
Journal of Reproductive Health and Medicine xxx (2016) xxx–xxx
A R T I C L E I N F O
Article history:
Received 2 May 2016
Accepted 21 June 2016
Available online xxx
Keywords:
Endometrial carcinoma (EC)
type 1 and type 2 EC
Elderly women
Luteinizing hormone (LH)
LH/human chorionic gonadotropin ( hCG)
receptors
Nongonadal LH/hCG receptors
Estrogens
Gonadotropin releasing hormone analogs
A B S T R A C T
Endometrial carcinomas (ECs) are the most common gynecologic malignancies, exceeding the incidence of
ovarian and cervical cancers in elderly women (post-menopausal) in Western countries. Evidence suggests
that it is a luteinizing hormone (LH) dependent disease. ECs overexpress LH/human chorionic gonadotropin
(hCG) receptors as compared with pre and post-menopausal endometria. Activation of the LH/hCG
receptors in primary and immortalized EC cells results in an increased cell proliferation and invasion,
which are mediated by cyclic AMP(cAMP)/protein kinase A (PKA) signaling, require the presence of LH/hCG
receptors, activation of b1 integrin receptors and an increase in the secretion of metalloproteinase-2
(MMP-2) in its active form. In addition to the endometrium, LH actions in the ovaries and adrenal glands
results in an increased secretion of androgens, which are aromatized into estrogens in the adipose and EC
tissues. LH also has direct effects in the pancreas, which results in an increase in insulin secretion, which in
turn can also stimulate ovarian stromal cell proliferation, luteinization, androgens secretion and
aromatization in adipose and EC tissues. LH is further elevated in post-menopausal women who develop EC
as compared with post-menopausal women who do not develop the disease. These findings support
complex network of LH actions that promote EC development in elderly women.
ß 2016 Published by Elsevier, a division of Reed Elsevier India, Pvt. Ltd.
* Tel.: +1 3053480659.
E-mail address: crao@fiu.edu
G Model
JRHM-33; No. of Pages 7
Please cite this article in press as: Rao CV. Luteinizing hormone is a primary culprit in the endometrial carcinoma development in
elderly women, J Reprod Health Med. (2016), http://dx.doi.org/10.1016/j.jrhm.2016.06.001
Contents lists available at ScienceDirect
Journal of Reproductive Health and Medicine
journal homepage: www.elsevier.com/locate/jrhm
http://dx.doi.org/10.1016/j.jrhm.2016.06.001
2214-420X/ß 2016 Published by Elsevier, a division of Reed Elsevier India, Pvt. Ltd.
2. It works through a complex network of actions in several organs
including the EC as well as ovaries, adrenals, adipose tissue and
pancreas.
2. Evidence linking LH to EC
Several earlier studies have suggested that LH might be
involved in the development of EC in post-menopausal women,
based on the findings that circulatory LH levels were further
elevated in women who developed EC as compared to those that do
not develop the disease.22–25
This suggestion has been validated by
a study which demonstrated that ECs overexpress LH/human
chorionic gonadotropin (hCG) receptors as compared with pre- and
post-menopausal endometria.26
This study also demonstrated that
the receptor overexpression increased with the stage of the
disease.26
Subsequent studies have confirmed the receptor
presence not only in ECs, but also in primary and immortalized
EC cells.27–35
The receptor expression was higher in carcinomas
than in the surrounding microscopically normal endometrium and
closely linked to aggressive tumor behavior.30
LH was found to be
mitogenic as well as to enhance invasion in primary and
immortalized EC cells.29,31,33
The EC cells that have higher LH/
hCG receptor levels, showed a greater invasive potential when
exposed to exogenous recombinant LH.33
These actions are cAMP/
PKA mediated and require the presence of the LH receptors.31
The
invasion, which is a prerequisite for metastasis, is promoted by an
activation of b1 integrin receptors, with a subsequent increase in
metalloproteinase (MMP-2) secretion in its active form.31
The
mitogenic, invasion enhancing potential and other effects of LH/
hCG have previously been demonstrated in normal cells.36–63
These normal processes may have been amplified in EC, which is a
hallmark feature of all carcinomas.
Circulatory LH appears to drive EC pathogenesis in elderly
women. These levels (total/bioactive) are elevated up to seven fold
in the women who have developed EC than the cohorts who do not
develop EC.22,64
Therefore, LH seems to be an important factor. But
it alone may not be sufficient, as most elderly women with
elevated LH levels do not develop the disease. Therefore, genetic or
epigenetic and other inherent risk factors may also be required.
3. LH actions in EC
LH has several effects in the normal human endometrium
that are relevant to implantation of blastocyst and its
limited invasion into endometrium and pregnancy continua-
tion.39,42–44,46,49–52,54–62,65,66
When some of the normal actions are
dysregulated, the potential exists for LH to initiate malignant
changes that might lead to the development of EC. The LH actions
in normal endometrial cells fall into proliferation, invasion,
angiogenesis, and apoptosis categories.39,42–44,46,49–52,54–62,65,66
Even though, the latter two have not been demonstrated in the
context of EC development, there is a reason to believe that they
may occur. For example, type 2 ECs are highly vascular and the
increased vascularity could come from the LH, which is a
vasoactive hormone in its own right. For example, uterine
vasculature contains LH/hCG receptors and their activation results
in the formation of new blood vessels as well as dilation of the
existing ones.54,67–71
4. LH actions in ovaries, adrenals, adipose tissue, and pancreas
may contribute to the EC development
The mechanism of LH action to induce EC may also involve its
actions in the ovaries, adrenals, adipose tissue, and pancreas,
through functional LH/hCG receptors in these tissues.72–78
The ovaries of post-menopausal women actively secrete
androgens from the stromal cell compartment and LH can
stimulate this secretion.79–95
The ovaries of women with EC are
even more active in androgens secretion than cohorts without
EC.85,89,92–94,96
The increased secretion comes from hyperplasia
and luteinization of stromal cells and greater elevation of LH
levels.22,63,64,96–99
The role of the adrenal glands in EC development is related to
an increase in LH levels, which can stimulate zona fasciculate to
secrete androgens. In fact, (a) age associated increase in LH levels
correlate with an increased adrenal function in post-menopausal
women,100–103
(b) hCG challenge increases adrenal androgens
secretion in older female macaques104
and finally (c) hCG can
stimulate androgens secretion from human adrenal cortical
cells.75
Adipose tissue involvement in EC pathogenesis is related to an
increased aromatization of androgens from adrenals and ovaries,
which is perhaps under LH and/or insulin control. However, there
is no evidence yet for the LH control, but this may not be a far-
fetched possibility, considering that it contributes to the
aromatase regulation in ovaries. Insulin, on the other hand,
seems to be able to regulate aromatase in fat tissue.105
Activation
of LH/hCG receptors has been shown to increase cell proliferation,
differentiation, and leptin secretion from preadipocytes.76
These
actions are mediated by cAMP/PKA independent mitogen
activated protein kinase yet (MAPK)/c-fos signaling.76
Whether
or how these LH actions could contribute to EC pathogenesis is not
known.
The involvement of the pancreas in EC development in post-
menopausal women is related to the hyperinsulinemia, a known
risk factor in type 2 ECs.4,5,106
In fact, EC patients often have
elevated insulin levels and an increased insulin resistance.106
The
higher insulin levels could come from LH stimulation of b-cells of
pancreas.77
However, it is not known whether LH can also
contribute to increased insulin resistance. Nevertheless, the
increased insulin levels can stimulate ovarian stromal cells
proliferation, luteinization, secretion of androgens, and their
aromatization in EC tissue.106–111
Post-menopausal women regardless of EC have elevated
androgen levels.84,92–95,100–102
These elevated levels come from
a secretion from adrenals as well as ovaries, both of which are
stimulated by LH.72,103,104
The androgens are then converted to
estrogens in adipose and endometrial tissues.111–114
This
conversion is increased in post-menopausal women who
develop EC, as compared to those who do not develop the
disease.109,112
These increases likely come from LH and insulin
stimulation because their levels are elevated during EC
pathogenesis64,106
and the tissues themselves contain their
receptors.64,105–107,110,115,116
In fact, insulin can regulate
aromatase in endometrial and adipose tissues.105,111
Whether
LH is also involved is not known. But it is not a far-fetched
possibility. Estrogens formed from androgens result in only a
small increase in circulation, perhaps due to differences in
metabolic clearance rates, conversions to other steroids and the
level and binding capacity of sex steroid binding globulin
(SHBG).92
The increased aromatization in EC tissue and potential
further stimulation by LH and/or insulin could result in a
high local estrogen concentration in the tumor microenviron-
ment. The role of these estrogens is not known, but they are not
likely to induce type 2 EC because the tumors do not contain
ER.1–3
What roles do these estrogens play, remains to be
investigated.
Fig. 1 presents the proposed model on how LH can induce type
2 EC in elderly women. Future research will undoubtedly bring
several modifications to this model.
C.V. Rao / Journal of Reproductive Health and Medicine xxx (2016) xxx–xxx2
G Model
JRHM-33; No. of Pages 7
Please cite this article in press as: Rao CV. Luteinizing hormone is a primary culprit in the endometrial carcinoma development in
elderly women, J Reprod Health Med. (2016), http://dx.doi.org/10.1016/j.jrhm.2016.06.001
3. 5. Estrogens versus LH
Estrogens are believed to be culprits in type I EC development
through the mitogenic actions.117,118
These actions are antago-
nized by progesterone, which promotes the differentiation of
endometrial epithelial cells.119
Thus, women who regularly
ovulate and produce progesterone rarely get EC.119
When the
cyclicity ceases and the balance tips in favor of estrogens, then
endometrial cells can continue to proliferate unabated, leading to
EC.119
This tipping can also happen in women who take only
estrogen containing birth control pills.120
The antagonism can also
explain why progesterone therapy works for type 1 ECs.119
Estrogens are not likely to be the culprits in type 2 EC
development because their circulating levels are very low and
there are no ER in the tumor. Conversely, LH are not likely to be the
culprits in type I EC development, because its levels are low, except
during a brief periovulatory period. However, LH/hCG receptors,
which are functionally coupled to physiological responses that are
required for pregnancy initiation and maintenance, are present in
endometrium.39,42–44,46,49–52,54–62,65,66
It is only when LH levels
are chronically elevated, followed by some type of dysregulation
which results in the receptor overexpression and perhaps post-
receptor changes, then the LH actions become relevant in type 2 EC
development. The molecular details of this dysregulation remain to
be investigated.
Pre-menopausal women with polycystic ovarian syndrome
(PCOS) have a 3-fold increase in EC risk, which is impacted by
the degree of obesity.121–128
These women have a higher total/
bioactive LH and androgen levels, increased insulin resistance
and low circulating estrogens, especially if they are not
ovulating.129–132
ECs arise from complex or atypical endometrial
hyperplasias in these women.28,123
Both simple and complex
hyperplasias contain higher LH/hCG receptors levels than
normal endometrium and the levels further increase from
simple to atypical hyperplasias.28
It is entirely possible,
therefore, that LH could also be a culprit in the EC development
in PCOS women.
There are two other hyperandrogenic conditions in which EC
risk also increases. One is hyperthecosis and the other is androgen
producing ovarian tumors.133,134
Insulin levels are elevated and
insulin resistance increases in these women.135
Even though ECs of
these women have not been investigated for the presence of LH/
hCG receptors, it is within the realm of possibility that LH could
also be a culprit in EC development in these pre-menopausal
women.
Even though hCG levels, surrogate for LH, are elevated during
pregnancy, they are not likely to cause EC. Quite to the contrary,
the life-time EC risk decreases with each pregnancy.136
This
pregnancy induced protection comes from progesterone, which
induces cell differentiation. Its levels are rather high to begin with
and they keep increasing to even higher levels during the second
half of pregnancy.
Setiwan et al. have suggested that the classification of ECs
requires a change due to a considerable overlap in risk factors for
type 1 and type 2 diseases.137
Moreover, not every women will
have exactly the same time course of hormonal changes as they
approach menopause and beyond. Therefore, we recommend
reclassification based on LH dependency. In the reclassification,
type 1 ECs are LH independent and type 2 ECs are LH dependent.
Estrogens will have different roles in both the diseases. In LH
independent disease, estrogens can initiate the disease through
their mitogenic effects. In LH dependent disease, estrogens have a
secondary role of increasing LH release from anterior pituitary
gland. In addition, elevation of free estrogens, due to a decrease in
SHBG in post-menopausal obese woman, can serve as a further
powerful stimulus for bioactive LH release.138
The same scenario
applies to pre-menopausal obese women with polycystic ovarian
disease.129
In both cases, obesity will be the primary trigger in
inducing the cascade of hormonal changes that are ultimately
responsible for EC development. Obesity is an important health
concern that costs the U.S. economy approximately $69 billion a
year.139
It increases an individual’s risk for many diseases,
including EC and several other forms of cancer.15,139
However,
not all post-menopausal obese women are likely to develop EC, due
Hypothalamus
Anterior
OvariesAdipose
Ɵssue
PancreasAdrenals
Endometrial
carcinoma
GnRH
LH
LH
LH
LH
Androgens Androgens
AndrogensAndrogens Estrogens Insulin
Insulin
LH
Fig. 1. Proposed model of LH induced type 2 endometrial carcinoma in elderly women. In this model, LH is a primary instigator. Besides direct actions in the endometrial
carcinoma tissue, its works through a number of other organ systems and all of which bear down on EC to drive the disease process. The molecular details of many of these
steps are unknown.
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elderly women, J Reprod Health Med. (2016), http://dx.doi.org/10.1016/j.jrhm.2016.06.001
4. to a lack of strong co-existing genetic predisposition and other
inherent risk factors. On the other hand, some post-menopausal
lean women may develop EC, because of the presence of a strong
genetic predisposition and/or the presence of other inherent risk
factors. Therefore, obesity and consequent elevation of LH levels
are important and can only predispose women to develop EC, when
genetic, environmental, life style and reproductive risk factors co-
exist. This reasoning should neither come as a surprise nor solely
applicable to EC. It is also important to point out that non-
hysterectomized post-menopausal women, regardless of obesity,
who take estrogen replacement therapy for the control of their
menopausal symptoms, are at an increased risk to develop EC, due
to incessant stimulation.118,120
6. Mechanism of LH actions in EC
The following mechanisms of action can be envisioned from the
known LH actions in EC, normal endometrial epithelial and in other
cells.36–63
1. LH binds to its cell surface receptors to activate them.
2. The activation results in the generation of second messengers
such as, cAMP/PKA, PKC, MAPK, b catenin/Wnt, and a cross talk
between them.
3. The second messengers can then regulate cyclins, cyclin
dependent protein kinases, b1 integrin receptors, active
metalloproteinase-2 secretion, pro and anti-inflammatory,
and apoptotic molecules, etc.
4. The receptor activation may also lead to other changes such as
the secretion of cytokines, growth factors, and eicosanoids.
5. LH may also modulate the immunity by regulating the immune
cells trafficking and their cytokines secretion in ECs.
All LH actions can be classified into non-genomic as well as
genomic. In both cases, initial cell surface receptor binding of LH is
necessary. After the binding, the non-genomic actions such as,
second messengers’ generation, activation/inactivation of kinases,
phosphorylation/dephosphorylation of proteins, ion flux changes,
etc. will commence. The non-genomic actions will be rapid and
may be required for sustaining the slow genomic actions. Non-
genomic changes can help in the genomic actions of LH, through
phosphorylation/dephosphorylation of transcription factors, their
nuclear import, subsequent binding to cis-acting elements, etc. The
genomic actions can involve up or down regulation of many genes
in the families of cell cycle, cell invasion, growth factors,
oncogenes, tumor suppressors, apoptosis inhibitory, and multitude
of others, whose identity remains unknown.
7. Need for further research
There is an obvious need for a great deal of further research for a
better understanding of the LH actions in type 2 EC development.
This research could focus on answering the following interrelated
questions.
1. What are the triggering factors for the LH/hCG receptor
overexpression in ECs?
2. What are the cellular, genetic and biochemical mechanisms that
LH uses to increase the cell proliferation, invasion, etc. in ECs?
3. Can LH induce EC pathogenesis in the absence of aromatizable
androgens from ovaries and adrenals or their aromatization in
fat and EC tissues?
4. Does LH upregulate aromatase and/or its catalytic activity in
adipose and EC tissues?
5. Can LH also increase the insulin resistance in obese EC patients?
6. How important are the insulin actions in ovarian stroma and in
EC for the disease development?
7. Can LH regulate immune cells migration and their secretion of
cytokines, chemokines, etc. in ECs?
The answers will enrich our understanding of complex basic
cellular, molecular, biochemical and genetic mechanisms that LH
employs to induce EC development. Such an understanding could
provide discovery path for novel therapeutic targets in ECs.
8. Therapeutic possibilities
When an elevated circulatory LH levels are the culprits in type
2 EC development, then the obvious treatment approach will be to
reduce the levels, which can be accomplished by treatment with
gonadotropin releasing hormone analogs (GnRHa). There are a
number of conflicting reports, however, on the success of GnRHa
treatment.140–148
The reported treatment failures could come from
the advanced disease stage, incomplete EC dependence on LH, low
LH/hCG receptor expression, etc. Complicating the interpretation
of the results are the findings that ECs contain GnRH receptors,
which could mediate the direct inhibitory effect of GnRH in
ECs.149–152
However, there is a report showing that GnRH induced
growth inhibition of EC cells does not require its receptors.146
ECs
seem to produce small amounts of hCG and how this production
impacts the EC development and/or its response to GnRHa
treatment remains unknown.34,153
Future therapies worth explor-
ing include, local delivery of pharmacologic LH/hCG receptor
inhibitors, receptor gene silencers, etc.
Conflicts of interest
The author has none to declare.
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