SEARCH RESULTS FOR: Menopause

Menopause contraindications to hormone replacement therapy

Uterine-Fibroids

Uterine Fibroids (Leiomyomas): Pathogenesis and clinical findings Early Menarche (onset of period) ↑ estrogen exposure in Obesity ↑ adipose tissue ↑ conversion of androgens into estrogen Ethnicity (African) ↑ amount of aromatase enzymes Family History Complex chromosomal rearrangements Myometrial Injury Hypoxia of myometrial cells Low Parity Lack of protective pregnancy-induced remodeling to myometrium Note: Approximately three-quarters of women have fibroids. Of these, only about one-quarter become symptomatic. Fibroids generally decrease in size after menopause and symptoms improve. Intracavitary Fibroid projects into uterine cavity ↑ Endometrial Surface Area ↑ endometrium to proliferate and lose during menstruation Age 40-50 lifetime Estrogen stimulates proliferation of uterine smooth muscle cells Benign proliferation of monoclonal myometrial (uterine wall/muscle) cells into discrete masses Uterine Fibroids (Leiomyomas) Benign tumours originating in and consisting of uterine muscle tissue Fibroids can be located in different areas of the uterus, including the following locations Authors: Emilee Anderson Reviewers: Danielle Chang Crystal Liu Yan Yu* Aysah Amath* * MD at time of publication Subserosal Fibroid grows adjacent to perimetrium into uterine muscle Enlarged uterus or pelvic mass on bimanual exam Irregularities in uterine cavity Transformation of normal myocytes into abnormal myocytes Submucosal Fibroid grows adjacent to endometrium into uterine muscle Intramural Fibroid is within the thickness of the myometrium Pedunculated Fibroid extends into pelvic cavity or uterine cavity on a stalk Spherical mass on ultrasound Fibroid ↑ intra-abdominal pressure and puts pressure on adjacent organs Enlarged Uterine/Pelvic Mass Repeat shedding over time Iron Deficiency Anemia Pelvic Pain Compression of stomach Fibroid takes up space Enlarged Abdomen Fibroid puts pressure on the cervix Dyspareunia Fibroid compress the bladder Urinary incontinence Fibroid compress the bladder outlet Difficulty with voiding Fibroid compress rectum Constipation Embryo cannot implant Infertility and/or recurrent pregnancy loss Menorrhagia Dysmenorrhea Sensation of abdominal fullness Early Satiety Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 5, 2020 on www.thecalgaryguide.com

abnormal-uterine-bleeding-aub-pathogenesis-and-clinical-findings

Abnormal Uterine Bleeding: Pathogenesis and clinical findings Authors: Joshua Yu, Karen Paik Reviewers: Ayaa Alkhaleefa, Parker Lieb, Hypothyroidism Hypothalamus senses ↓ serum thyroxine ↑Thyrotropin releasing hormone (TRH) release from hypothalamus ↑Prolactin (see Feedback Loop: Prolactin) Exogenous estrogen (e.g. estrogen-only birth control) ↑ Peripheral adipose tissue ↑ Aromatase (enzyme present in adipose tissue) ↑ Conversion of androgens to estrogens (aromatization) Excessive stress, exercise, low body mass (mechanism unclear) ↓ Hypothalamic gonadotropin releasing hormone secretion ↓Luteinizing hormone and follicle stimulating hormone release from pituitary ↑ Estrogen Heavier bleeding Angiogenesis in tumour tissue Polycystic ovarian syndrome (see slide) Pelvic inflammatory disease Immature hypothalamic- pituitary-ovarian axis (an immature axis is transient in most females) ↓ Positive feedback of estrogen in late follicular stage No LH surge Adenomyosis (endometrial tissue grows into uterus muscular wall) Endometrial polyps Retained products of contraception Infection Inflammation of endometrium Endometrium is more fragile Anovulatory Bleeding Leiomyoma (benign tumour in myometrium) Tara Shannon, Hannah Yaphe, Dr. Sarah Glaze* * MD at time of publication Ovarian Scarring Foreign bodies Intrauterine device perforation Physical trauma Impaired follicle maturation Anovulation Corpus luteum does not form No ovarian progesterone production ↑ Estrogen to progesterone ratio Proliferative effect of estrogen unopposed Endometrial proliferation No progesterone to organize growing endometrium Disorganized endometrium overgrows and sloughs off Irregular bleeding Menopause Premature ovarian insufficiency Intermittent congestion of polyp blood supply Transient ischemia and slight polyp necrosis Altered growth factor production Vascular dysregulation and leakier vessels Coagulopathies (e.g. von Willebrand disease) Impaired hemostasis Invasion of normal tissue ↓ Estrogen (hypoestrogenism) Atrophy of endometrium and vulvovaginal tissue Dry endometrial surfaces (↓ fluid to prevent friction) Endometrial carcinoma Micro- erosions of epithelium Inflammation Evidence unclear Heavier and more irregular bleeding Spotting Heavier and more irregular bleeding Light bleeding and spotting Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 2, 2022 on www.thecalgaryguide.com

epithelial-ovarian-cancer-subtypes-molecular-alterations-risk-factors

Epithelial Ovarian Cancer: Subtypes, Molecular Alterations & Risk Factors Risk factors associated with developing specific subtypes of epithelial ovarian cancer Authors: Brian Yu Chieh Cheng Reviewers: Ayaa Alkhaleefa, Parker Lieb, Tara Shannon, Sarah Glaze* * MD at time of publication No known subtype specific risk factors Smoking Introduction of carcinogenic material ↑Rate of cancer causing genetic mutations 2) Mucinous carcinoma Ovarian endometriosis (implantation of endometrial tissue on the ovaries) ↑ Chance of endometrioma (cyst comprised of endometrial tissue) formation in ovaries See Endometriosis Slide Familial BRCA1 or BRCA2 mutation Impaired double strand DNA repair mechanism results in accumulation of DNA damage 5) High grade serous carcinoma Lynch syndrome (autosomal dominant mutations in DNA repair genes) Impaired DNA mismatch repair mechanismà accumulation of DNA damage 1) Low grade serous carcinoma 3) Clear cell carcinoma 4) Endometrioid carcinoma Either clear cell, endometrioid carcinomas, or a mix of both subtypes General risk factors for developing all epithelial ovarian cancer (unknown pathogenesis) 1. Old age 2. Family history of breast or ovarian cancer 3. Post-menopausal hormone replacement therapy 4. Irregular age of menarche & menopause 5. High number of lifetime ovulation events / nulliparity Alteration in genes like KRAS, NRAS, BRAF, ERBB2 & CDKN2A Alteration in genes like ARID1A, PIK3CA & ERBB2 Alteration in genes like POLE & TP53 Molecular alterations in genes like TP53 and/or CCNE1 Molecular alterations commonly associated with specific epithelial ovarian cancer subtypes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Findings Complications Published August 30, 2022 on www.thecalgaryguide.com

Menopause

Menopause: Pathogenesis and Clinical Findings Perimenopause/Menopausal Transition: Phase preceding last menstrual period in which the first symptoms may occur. Many clinical findings of menopause can occur in perimenopause. 1-2 million primordial follicles first appear in fetal ovaries in the end of the first trimester of the mother’s pregnancy Typically beginning in adolescence, puberty triggers physiological and anatomical changes Menarche (commencement of menstrual cycles) See relevant slide: Menstrual Cycle Physiology: Ovarian Cycle – Brief Overview Each cycle involves ovulation, during which an oocyte is released from the ovary’s dominant follicle into the Fallopian tube Some non-dominant follicles degenerate in a process known as atresia Menstrual cycle stops Menopause marks 1 year since last menstrual cycle ↓ Fluid transudatio n from blood vessels of vaginal wall ↓ Vaginal lubrication Vaginal tissue becomes thinner and more easily irritated Over time, fewer follicles remain in the ovary Some cycles become anovulatory (no oocyte is released from ovary) ↓ Ovulation causes prevents thickening of the endometrial lining ↓ regularity and frequency of periods Ovaries eventually stop releasing oocytes ↑ Oxidative stress- induced apoptosis of dermal fibroblasts Remaining non-dominant follicles become less sensitive to LH and FSH Since follicular cells are responsible for estrogen production, less follicles result in reduced estrogen production ↓ Expression of serotonin receptors in the CNS ↓ LDL receptor expression and ↑HMG- CoA reductase activity ↓ Regulation of the production and clearance of LDL ↑ LDL Cholesterol levels Author: Sunawer Aujla Reviewers: Ashar Memon Yan Yu* * MD at time of publication ↓ Serotonin activity ↓ Density of ↓ Healthy vaginal flora ↑ pH of vaginal fluid ↑ Spread of bacteria otherwise unable to survive in low pH environment Recurrent urinary tract infections ↓ Calcitonin ↑ Sensitivity of bone mass to Parathyroid Hormone ↑ Activation of osteoclasts Mechanism is likely multifactorial and the subjective symptoms of menopause may contribute Depression 5HT receptors in thermoregulatory region of hypothalamus ↑ Inhibition of sexual responses initiated in prefrontal cortex ↓ Libido 2A ↓ Collagen, elastin, and hyaluronic acid ↓ Proliferation of smooth muscle fibers ↓ Inhibition of osteoclasts Narrower thermoregulatory zone Injury to epithelial tissue in multiple areas of the body Atrophy of bladder and urethra epithelium Urinary incontinence More bone resorption than formation Osteoporosis See relevant slide: Osteoporosis: Pathogenesis and risk factors Sometimes, for unknown reasons, core body temperature increases above upper threshold of narrowed thermoregulatory zone Hot Flashes Sudden, temporary onset of body warmth, flushing, and sweating Sometimes, for unknown reasons, core body temperature decreases below lower threshold of narrowed thermoregulatory zone Chills Sudden, temporary onset of shivering, tingling, cold feeling Atrophy of vaginal epithelium Dyspareunia Pain during sexual intercourse ↓ Integrity of of blood vessels Atherosclerosis ↑ Risk for cardiovascular disease Genitourinary Syndrome of Menopause Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published June 7, 2023 on www.thecalgaryguide.com

Cystocele

Cystocele: Pathogenesis & Clinical Findings Authors: Emily Cox Reviewers: Riya Prajapati Michelle J. Chen Dr. Rebecca Manion* * MD at time of publication Obesity Pregnancy Chronic constipation Chronic cough Vaginal childbirth Vacuum-assisted or forceps-assisted vaginal birth Pelvic surgeries (e.g. hysterectomy) Connective tissue disorders (e.g. Marfans, Ehlers- Danlos Syndrome) Genetic susceptibility (e.g. Type III collagen gene abnormality Menopause Visceral fat places pressure on pelvic floor structures Growing fetus places pressure on pelvic floor structures Straining and bearing down on pelvic floor Muscle tearing and damage Disruption of nerves, loss of bladder structural support, and disruption of fascia and muscles Collagen impairment Depletion of ovarian follicles leading to ↓ in estrogen production ↑ Intra-abdominal pressure Transfer of intra- abdominal pressure to pelvic floor Pelvic floor muscles and pelvic floor fascia become weakened Pelvic tissue and muscular atrophy Loss of tissue function and structure support that collagen provided ↓ Stimulation of collagen production ↓ Estrogen levels Pelvic Organ Prolapse Quantification (POP-Q) System: Grade 1: Bladder descends 1 cm above the hymen Grade 2: Bladder descends to ≤ 1 cm above or below hymen Grade 3: Bladder descends past the hymen but 2 cm less than total vaginal length Grade 4: Complete vaginal prolapse Mechanical obstruction of bladder and urethra Urinary retention Descended bladder creates pressure in vagina Pressure/bulging sensation Symptoms of voiding dysfunction (e.g. incomplete emptying/frequency/ urgency/nocturia) Vaginal intercourse puts pressure on descended bladder Activates pain receptors Dyspareunia (painful sex) for some patients Cystocele Descent of bladder through anterior vaginal wall Hydronephrosis/ hydroureter Recurrent UTI Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 5, 2024 on www.thecalgaryguide.com

Ankle Fracture

Ankle fracture: Pathogenesis and clinical findings High mechanical force to ankle Risk factors Age Post-menopause ↓ Osteoblast activity Twisting force (e.g. sports injury) Crushing force (e.g. limb Loading force entrapment beneath heavy object) (e.g. fall) Force exceeds mechanical strength of bone Ankle eversion or inversion Osteoporosis Compromised bone scaffolding & repair impairs the structural integrity of bone. Force required for fracture is lowered Ankle Fracture (Fracture of the talus and/or the distal 6 cm of the tibia and/or fibula) Fractured bone is displaced through the dermal layers Open Fracture Compromised dermal layers create an opportunity for pathogens to enter the wound site Infection Multiple malleoli are fractured within the ring of the ankle Lack of ligamentous & bone support makes ankle joint unstable Displacement of bone from fracture site Misalignment of bone segments prevents regeneration & union Malunion of unreduced fracture Ligamentous injury occurs concurrently from excessive tensile force Fractured bone disrupts surrounding vasculature Hyaline cartilage of the articulating surface is damaged Trauma induces synovitis, chondrocyte apoptosis, & necrosis Fractured bone disrupts surrounding peripheral nerves Numbness Localized Pain Pain is induced when the patient attempts to weight bear Inability to weight bear Authors: Ethan Smith Reviewers: Nojan Mannani Michelle J. Chen Dr. Gerhard Kiefer* * MD at time of publication Platelets are exposed to the extravascular environment, thereby releasing platelet derived factors & complement factors Plasma coagulation cascade is activated Chondrocyte dysfunction in proliferation Reduced synovial functioning ↑Vascular permeability from inflammatory cytokines Protective hematoma forms in the joint space Hyaline cartilage loss Lost cartilage over time degrades proper articulation & causes joint narrowing, osteophytes, subchondral sclerosis Post traumatic osteoarthritis Edema Fluid in the joint space changes position of bony articulations Bruising Restricted range of movement Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 30, 2024 on www.thecalgaryguide.com

Genital Prolapse

Instrument-assisted vaginal deliveries (especially forceps) ↑ risk of levator muscle avulsion Pelvis widens during Valsalva maneuver (straining downwards to ↑ intra-abdominal pressure) ↑ Support needed to hold pelvic organs, which may eventually fail Genital Prolapse: Pathogenesis, clinical findings, & complications Pregnancy Levator ani muscle is injured or denervated due to overstretching & or compression during labour Levator ani muscle loses tone Genital hiatus opening enlarges Pelvic diaphragm descends & forms a funnel shape Ligamentous & connective tissue (e.g., arcus tendineus fascia pelvis, arcus tendineus levator ani, uterosacral ligaments) bear the ↑ abdominal pressure load Ligamentous & connective tissue stretch & may eventually fail with time ↑ Internal pressure from pelvic organ tissues pushes against pelvic muscles Hysterectomy Disruption to pelvic structural supports (particularly uterosacral ligament), pelvic blood supply, & or innervation during operation ↓ Pelvic organ support, which may fail with time Authors: Sara Cho Reviewers: Michelle J. Chen Jessica Revington Rachel Wang* * MD at time of publication Unclear mechanism Pelvic & or low back pain Dyspareunia (pain during intercourse) Legend: Pathophysiology Mechanism Conditions with impaired collagen quality (e.g. Ehlers-Danlos syndrome, Marfan syndrome) Alterations in collagen & elastin synthesis Dysfunction of pelvic connective tissue Aging/menopause ↓ Systemic estrogen concentrations ↓ Smooth muscle cell proliferation & collagen synthesis in tissues with estrogen receptors (e.g., endopelvic fascia, arcus tendineus, levator ani, uterosacral ligament) Chronic cough Frequent contraction of abdominal & pelvic muscles Chronic constipation Patient constantly bears down, contracting abdominal & pelvic muscles Genetic factors (e.g., family history of prolapse, urinary incontinence, abdominal or inguinal hernia) Obesity Surrounding adipose tissue ↑ intra-abdominal pressure ↑ Stress on pelvic supporting structures Repeated ↑ in intra- abdominal pressure Combination of risk factors that contribute to, predispose, promote, or worsen prolapse Sign/Symptom/Lab Finding ↓ Pelvic organ support, which may fail with time Genital Prolapse Vaginal or uterine descent through the introitus (genital opening) Rectum pushes against the vaginal wall & widens the anorectal angle (angle between anal canal & rectum) Fecal incontinence Published Aug 25, 2025 on www.thecalgaryguide.com Weakened pelvic floor muscles provide ↓ structural support & ↑ hypermobility of the urethra & bladder neck Urinary incontinence Complications

Endometriosis

Endometriosis: Pathogenesis, clinical findings, & complications Risk factors Theories of endometrial tissue migration Genetic causes (family history & specific gene loci) Transfer of endometrial tissue away from the uterus during pelvic surgery, vaginal delivery, or cesarean section Sampson’s theory: Retrograde flow of endometrial tissue through fallopian tubes Long menstrual flows (↑ retrograde menstruation) Coelomic metaplasia theory: Undifferentiated mesothelial cells from the peritoneal cavity differentiate into endometrial cells during fetal development. May also occur in patients with testes Implantation theory: Menstrual endometrium implants onto pelvic structures ↓ Cellular antioxidant capacity (↑ cell damage) Alcohol use (mechanism unclear) Early menarche (↑ estrogen exposure) Stem cell theory: Endometrial stem/ Embryonic rest theory: Residual progenitor cells from menstrual embryonic cells from Müllerian Dissemination theory: Endometrial blood or neonatal uterine bleeding or Wolffian ducts are misplaced tissue transported through bloodstream implant in the pelvic cavity during organogenesis or lymphatics to extrauterine structures (e.g., brain, pericardium) Cells differentiate into endometrial-like tissue Ovary releases estrogen & progesterone Endometriosis Endometrial glands & stroma (structural support tissue) found outside the uterus Ectopic endometrial-like tissue on bladder Ectopic endometrial-like tissue in posterior cul-de-sac Monthly proliferation (by estrogen) and stabilization (by progesterone) of endometrial tissue Chronic inflammation of surrounding tissues & fibrosis/adhesion formation Tissue inflammation & fibrosis/adhesions push on & displace pelvic organs Ectopic tissue abnormally activates nerve signaling pathways responsible for bladder contraction Bladder wall contractions activate nociceptors (pain sensors) Penetrative intercourse involving the posterior vagina applies ↑ pressure to tethered & immobile pelvic structures Feces moves down colon into rectum & applies pressure to the tethered rectum Monthly progesterone withdrawal Dyspareunia (pain with deep intercourse) Dyschezia (pain with bowel movements) ↑ Urinary frequency & urgency Pain with micturition (urination) Endometrial tissue sloughs off from a basal tissue layer (menstruation**) Extra-uterine endometrial- like tissue cannot evacuate the implantation site Retrograde menstruation in ovary ↑ the presence of ectopic endometrial-like tissue & blood (mechanism poorly understood) Old blood fills endometrial-like tissue on ovary Endometrioma (chocolate cyst) Chronic cyclical local inflammation (release of pro-inflammatory chemicals) Nociceptors near ectopic endometrial-like tissue activate Pain signals & release of inflammatory mediators subsides over time Cyclic dysmenorrhea (menstrual pain) Repair of inflammation Ectopic endometrial-like tissue becomes fibrotic (scarred) Significant ↑ scar tissue Nodule formation ↓ Hormone levels post-menopause Accumulation of inflammatory fluid within scar tissue ↑ Risk of scar tissue obstructing or kinking fallopian tubes Endometrial tissue stops proliferating Hormone-dependent symptoms (e.g., dysmenorrhea) cease Cyst formation Embryos unable to pass through fallopian tube to uterus Author: Joshua Seto Kayla Nelson Reviewers: Yan Yu Sean Spence Jessica Revington Infertility Colin Birch*, Rachel Wang* * MD at time of publication **See corresponding Calgary Guide slide Legend: Published December 20, 2013, revised September 24, 2025 on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications