Presentation on theme: "Today: 4/24/06 Female Reproductive System Aging"— Presentation transcript:
1 Today: 4/24/06 Female Reproductive System Aging Hormone Replacement Therapy
2 Terminology Menopause Permanent Cessation of Menstruation Permanent Loss of Ovarian FunctionNo reproductionFunctional consequences of low estrogens/progesteronePerimenopause1 year before until 1 year after menopausePostmenopauseFrom menopuase until deathPremenopauseBefore menopause
4 Ovary Characteristics OvariesContain germinal cellsContain endocrine producing cellsThecalGranulosaDetermine secondary structures and sexual characteristics
5 Cells in hypothalamus secrete GnRH (gonadotropin releasing hormone) which reaches through the portal blood system the anterior pituitary where it stimulates the secretion of gonadotropins FSH & LHFSH stimulates ovary to produce estrogensLH stimulates release of the ovum in oviduct and production of estrogen and progesterone
6 Endocrinology GnRH: Gonadotropin Releasing Hormone PeptideHypothalamusFSH, LH: Follicle Stimulating Hormone and Luteinizing HormonePeptidesAnterior pituitary gonadotrope cellsE, P: Estrogens and ProgesteroneSteroidsE from follicle cells and corpus luteumP from corpus luteum
8 Hormonal Changes From Aging Ovarian Steroidal HormonesEstrone levels early in the cycle in older ovulatory womenPossible due to LH/FSH alterationsEventually, H-P-G axis is unable to generate LH surge needed for ovulationGonadotropins:LHChange to pulsatile pattern:Duration, FrequencyFSH“Monotropic FSH ”1st Noticed prior to any change in cycle length
9 Fertility Changes and Perimenopause Fertility and Fecundity DecreaseOvulatory cycle continues after onset of perimenopauseCycle length becomes more variableShortening of follicular phaseNo change in luteal phasePeak fecundity occurs at 24, with a gradual decrease to 35, and a rapid decrease after 35
10 Ovarian Structural Changes Abnormalities in Older OocyteChange in microtubule and chromosome placement at the second metaphase of meiosisMay be linked to increased aneuploidy (unbalanced chromosomes) seen in offspring of older womenDeclining Follicular Reserve2 Million Primordial Follicles during fetal developmentDeclines to 1 million at birth and 250,000 by pubertyPrimordial Follicles develop to primary and secondary follicles independent of hormone statusIn the absence of LH/FSH, follicles undergo atresiaOnce follicles are depleted, ovarian hormone production declines
11 Menopause Symptoms Hot Flashes Symptoms Most common reported symptom: % of women report signs of hot flashesAsian women have much lower rate10-25 % ReportedPossibly due to genetics, diet, lack of reportingSymptomsSweatingIncreased Skin ConductanceIncreased Core Body TemperatureIncreased Metabolic RateIncreased Skin TemperatureHot flashes appear to be the result of noradrenergic control independent of estrogen regulationERT alleviates the symptoms of hot flashesAdrenergic receptor agonists also show promise for treatment
12 Menopause Effects on the Reproductive Tract Reproductive targets for steroidal hormones experience atrophy following menopauseIn addition, these more specific changes are seen:VaginaDrynessDecreased VascularityDecreased SecretionsIncreased Risk of InfectionsOvariesBecome more fibrotic as follicles diminishUterusLoses Weight and Volume
13 Effects on Non-Reproductive Steroidal Targets SkinThinning of epidermisAtrophy of sebaceous glandsIncreased sensitivity to temperature, humidity, and traumaBladderGeneral AtrophyResults in urinary incontinenceHairBody hair undergoes redistribution
14 Menopause and Non-reproductive Targets Skeletal SystemOsteoporosisDecreased bone mass following menopause that appears to be the result of declining estrogen levelCentral Nervous SystemPsychologicalAnxiety/DepressionCognition/MemoryCardiovascular SystemPossibly due to role of estrogen in lipid metabolism
15 Osteoporosis Cell Types: Osteoblasts: form new bone (build) Osteoclasts: resorption of old bone (chew)Osteocytes: mature bone cells that maintain the bone matrixOsteogensis is the formation of new bone
16 Why Menopause? Life span of a species and survivability of offspring Women have survived to an age where natural selection is no longer favored as the maintenance of the reproductive systemMenopause may be a pleiotropic effect of genes that had value earlier in lifeMenopause may carry advantage for survival of speciesNon-reproducing species members to care for young“Surrogate Mothers”
17 Questions What are the major female reproductive changes with aging? What is menopause?What are some of the non-reproductive effects of menopause?What are the reproductive hormones in the female reproductive tract and how are they controlled?
19 Anatomy of the Male Reproductive Tract In humans the principal reproductive organ is the brainIn addition to the brain, the male reproductive system consists of the:TESTISPrimary sex organ suspended outside of the body inthe scrotumSecondary male sex organs include:EPIDIDYMIS,VAS DEFERENS,EJACULATORY DUCTSwhich carry sperm to the urethraSEMINAL VESISCLES, PROSTATE, & BULBOURETHRAL GLANDSwhich secrete seminal fluidPENIS with URETHRAthrough which flow both urine and semen
20 A simplified version of the male reproductive endocrinology: The hypothalamus releases GnRH into the circulatory system and, through blood, directly into the pituitary.GnRH triggers the release of the pituitary LH and FSH that stimulate the testes to testosterone secretion and sperm production.
21 The testis, the male primary reproductive organ, contains three types of cells, allnecessary for reproduction:the GERM CELLS or GAMETES,involved in fertilization.the INTERSTITIAL CELLS of LEYDIGthat secrete testosterone, the major androgenthe SERTOLI CELLS with secretory and reproductive functions
23 With Age:On the average, the male reproductive function remains normal (or only slightly diminished in some individuals) until advanced old age (80+ years) when it decreasesSubtle changes include:GnRHSensitivity of androgen secretion to LHSensitivity of negative feedback between GnRH and LH
24 Serum LH concentration Young OlderYoung OlderSerum LH concentrationWith aging, loss of high-amplitude LH pulses despite normal or increased pituitary LH storesSerum testosterone concentrationWith aging, decreased responsiveness of testis androgen secretion to LH
26 The Prostate and Testosterone Table 19-12The Prostate and TestosteroneThe healthy prostate is dependent on androgens for growthIn the prostate: testosterone dihydrotestosterone (DHT)The enzyme catalyzing this reaction is 5--reductaseDHT stimulates growth of the prostate
27 Normal Aging of the Prostate Table 19-13Normal Aging of the ProstateAfter age 40:Outer regions:Atrophy of smooth muscle and proliferation of connective tissueFlattening of secretory epitheliumInner region:Increase in the number of cells present (hyperplasia)After age 60:Slower, but more uniform atrophy of the prostateAccumulation of prostate concretions
30 Treatment of Prostate Cancer Depends onLife expectancyOverall health statusPersonal preferencesSize of the prostateState of diseaseTreatments include:Watchful waitingSurgeryRadiation TherapyHormonal TherapyCryotherapy**PSA controversy pp. 353, 354**
31 Questions What are the male reproductive changes with aging? What are the changes in the prostate with aging?What are the hormones involved in the male reproductive tract and how is their release controlled?
33 Hormone Replacement Therapy Involves the attempt to replace, or substitute, the lost constituent with a similar exogenous substance with comparable properties and actionsDose, duration, metabolism, target cells, and side effects
34 Replacement Therapy Problems in Aging Complexity of endocrine systemLoss or insufficiency of endogenous hormonesTarget cells for hormones are themselves aging and this may effect their responsivenessChanges in hormones and their targets due to disease and degenerative processes
35 Hormone Replacement Strategies Adrenal Sex Steroids and DHEAGrowth HormoneInsulin (as in Laura Epstein’s lecture 4/14)Reproductive Hormones
36 Dihydroepiandrosterone (DHEA) DHEA is the principal adrenal androgen*Note-Does not bind androgen receptorDHEA(S) concentrations change throughout the human lifeDHEA(S) levels are lower in women than menIncreased mortality is associated in men with a lower DHEA(S) baseline, but not in women
37 DHEA and Aging DHEA Replacement beneficial in: Epidemiological Evidence (DHEA low levels)cardiovascular mortalityFound in:Autoimmune diseasesDementiaBreast cancerDHEA(S) levels may be indicative of a severe disease or predictive of a future diseaseDHEA Replacement beneficial in:Adrenal InsufficiencyHealthy Elderly?No increase in well being, cognition, nor sexualityElderly withimpaired mood,cognition andsexualfunction?
38 Growth Hormone and Aging Study in 1990 demonstrated in small group of elderly men that GH and IGF I levels were reduced:12 out of 21 men injected with hGH over a 6 month period showed small increases in muscle mass and bone density (10-14%)Suggests that GH might be responsible in part for decreased muscle and bone in elderly
39 Role of GH in AgingGH and IGF-I serum levels decrease in some elderly and nocturnal peak is lower or absentPossibly due to:Decreased GHRHIncreased GHIH (somatostatin)Stress
40 Effects of GH Treatment 1998 study of ICU patients found:Mortality increased from 19% to 44% in patients having GH therapy for 7-14 daysLength of hospital stay was prolonged by GH therapyAttributed to:Decreased immune functionIncreased insulin resistanceMulti-Organ Failure
41 Types of Hormones Used in Post-Menopause EstrogensAlone or with progestinTypes and route of administrationOptimal dose is the lowest dose to treat symptoms over the shortest durationProgestinsWith Estrogen to reduce risk of endometrial cancerCardiovascular risks outweigh benefitsOther products for osteoporosis treatment
42 Risks of HT Estrogen + Progestin Increases Risk of: Decreased Risk of: Breast CancerHeart DiseaseStrokeBlood ClotsDementiaDecreased Risk of:Hip Fractures (Osteoporosis)Colon Cancer
43 Benefits of HRT Relieves Short-Term Symptoms of Menopause: Hot FlashesSweatsDisturbed SleepMay also help prevent colon cancer and age-related vision loss
44 Alternatives to Hormone Therapy? (Recommendations from the Mayo Clinic) Maintain a Healthy Heart:Don't smoke.Be physically active.Eat a low-fat, high-fiber diet, plentiful in fresh fruits and vegetables.Maintain a healthy weight.Manage high blood pressure.Keep cholesterol and triglyceride levels in check.Control diabetes.Avoid excess alcohol.Healthy BonesCalcium and vitamin D. Make sure you're getting enough of these nutrients in your diet to keep your bones strong.Exercise. Regular physical activity — especially weight-bearing exercises such as walking or dancing — can help keep your bones strong and healthy.
45 QuestionsWhat are the risks and benefits of post-menopausal hormone replacement therapy?What are some of the challenges of hormone replacement therapy?