Amenorrhea, abnormal uterine bleeding pattern, inflammation/infection of the female reproductive tract, benign growth/aberrant tissue of the female reproductive tract, cancer of the female genital structures, diethylstilbestrol

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Colorado State University
Biomedical Science
BMS 460
D.Rao Veeramachaneni

11 December Exposure to chemicals that target preantral to ovulatory follicles may impair steroid production and thereby block ovulation, leading to infertility that may be reverted upon removal of exposure PAHs, pesticides, plasticizers, metals, solvents and a variety of endocrine-disrupting chemicals → impaired steroidogenesis, impaired ovulation, abnormal cyclicity → infertility until the exposure is ceased StAR → cholesterol → pregnenolone via CYP45011a1 Progesterone via 3βHSD → androstenedione via CYP45017α DHEA via CYP45017α → androstenedione via 3βHSD Androstenedione → testosterone via 17βHSD → E via 2YP45019 A Survey of Causes of Amenorrhea Primary Absence of menses in a phenotypic female by 16 years of age Hypothalamus Anorexia nervosa Strenuous exercise Isolated GnRH deficiency Congenital defects Tumor Pituitary Prolactinoma Hyperprolactinemia Hypopituitarism Thyroid Hypothyroidism Adrenal Congenital adrenal hyperplasia Adenomas/carcinoma Ovarian Ovarian failure Polycystic ovary disease 17-Hydroxylase deficiency Vaginal Vaginal agenesis Transverse vaginal septum Imperforate hymen Testicular feminization Secondary Absence of menses for 3 or more years in a previously menstruating woman Hypothalamus Anorexia nervosa Weight loss Strenuous exercise Pseudocyesis Systemic disease Post-pill amenorrhea Tumor Pituitary Prolactinoma Hyperprolactinemia Thyroid Hypothyroidism Hyperthyroidism Adrenal Congenital adrenal hyperplasia Adenomas/carcinoma Cushing’s disease Ectopic ACTH Ovarian Ovarian failure Resistant ovary syndrome Tumors Extrauterine Ectopic pregnancy Uterine Intrauterine pregnancy Trophoblastic disease Uterine synechiae Abnormal Uterine Bleeding Patterns Metorrhagia Bleeding between menstrual periods Hypomenorrhea Deficient amount of menstrual flow Oligomenorrhea Infrequent menstruation Polymenorrhea Increased frequency of menstruation Menorrhagia Debilitating increase in the amount and duration of menstruation Endometrial polyps, adenomyosis, or leiomyomas Dysmenorrhea Primary Not related to any identifiable pathologic condition Excessive production of prostaglandins Promote uterine contractions and ischemia of endometrial capillaries resulting in cramping pain Treat by targeting the pathways for the synthesis of eicosanoids Anti-inflammatory steroids (e.g., cortisol) inhibit phospholipa2e A Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase Secondary Associated with disorders such as leiomyomas, pelvic adhesions, or endometriosis Prostaglandins produced by the endometrium in response to decrease in plasma P and E (consequent to CL regression) cause vasoconstriction and uterine contractions Synthesis of arachidonic acid and its derivatives can be inhibited by several drugs – steroids (target phospholipase A ), NSAIDs (e.g., aspirin; target COXs), and specific cox- 2 inhibitors Action at different levels targeting different enzymes Inflammation and Infection of the Female Reproductive Tract Pelvic inflammatory disease The female reproductive system is extremely prone to infections Ascending infections; STD Descending infections; systemic If the infection is recurrent, as in chronic PID, PID is a major cause of pain and suffering When underlying connective tissue is also involved, PID is called parametritis Sequelae Tubal block: infertility Inflamed mucosa: tubal/ectopic pregnancy Other health problems; e.g., peritonitis ~1 million women are treated for PID each year in USA Vulvovaginitis Fungal infections (Candida albicans) account for ~50% Estrogen supplementation is a risk factor (by increasing glycogen content in vaginal epithelium) Benign Growth and Aberrant Tissue of the Female Reproductive Tract Uterine leiomyoma Most common form of uterine tumors Those that persist beyond menopause may lose smooth muscle cells and contain only stroma – fibroids The tumors may be subserosal, intramural, or submucosal Subserosal and submucosal tumors may be pedunculated
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