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Details Title: Ovarian Aging Pathophysiology Description: 4.18.07 Total Flash Cards: 47 Created: 04/23/2007 05:44:02	To study from this set of flash cards, or to create your own your own study flash cards, register HERE. If you are already a registered user, CLICK HERE.
Cards Term Why is there such a divergence between gonadal aging between the genders? Definition Women’s reproductive capacity has a defined endpoint due to oocyte loss resulting in menopause Spermatogenesis in men occurs throughout their lifetime Term What is the Impact of ovarian aging both normal and aberrant is individual, clinical and societal? Definition 1. Female infertility 2. Human longevity and the length of time that women live post menopause 3. Morbidity associated with age-appropriate and premature menopause --- Cardiovascular disease -Osteoporosis -Urogenital atrophy -Quality of life Term What are 3 prototypic aberrant states of ovarian phys? Definition Turner’s Syndrome , Chemotherapeutic/radiation exposure, Autoimmune premature ovarian failure Term What are 2 basic ovarian functions? Definition 1. Reproductive capacity: -The ovary houses female germ cells – oocyte (Maturation and ovulation one oocyte on a monthly basis ) 2. Steroidogenesis -Responsive primarily to pituitary gonadotropins (FSH, LH) -Cyclic production of estradiol and progesterone -Production of testosterone and peptide hormones Term At week 4, what is going on with ovarian development? Definition Appearance of Primordial Germ Cells in Yolk Sac , Migration of Germ Cells to Genital Ridge , Germ Cell Mitosis Term At week 6, what is going on with ovarian development? Definition Germ Cells Arrive at Genital Ridge , Sex Cord Formation Supports Germ Cells. At this stage, undiff gonads Term Reminder: Definition Reminder: When germ cells arrive at genital ridge reproductive tract is still undifferentiated. The development of uterus, fallopian tubes and upper vagina occurs in the absence of a Y chromosome which would otherwise drive differentiation toward a male pathway. Term At week 8-12, what is going on with ovarian development? Definition Ovarian Differentiation , Reproductive Tract Differentiation , Meiotic Arrest (Prophase I) , Initiation of Meiosis Oogonia become oocytes Term At week 16-20, what is going on with ovarian development? Definition Ovarian Follicular Formation , Max Oocyte Number Achieved: 5-7 million Term which 2 processes occur regarding oocytes that decrease their numbers? Definition oogonia decreases, and oocytes decrease Term Why is the ovary not dormant? Definition The ovary is not dormant despite its prepubescent state : 1. Waves of incomplete follicular development followed by atresia 2. No stimulation of the ovary by pituitary gland 3. Minimal estrogen production No ovulation occurs Term At what time does suppression of gonadotrophin first occur? Definition Suppression of gonadotropin levels usually occurs by one year of age Term what are 2 types of follicular loss? Definition tonic and FSH stimulated Term what is the amount of time required for development from the primordial follicle stage to ovulation to occur? Definition (85 days) Term How is 1 follicle chosen? Definition we don't know...or the amount of follicular atresia that occurs at multiple steps in the process in order for one dominant follicle to emerge and be ovulated. From primordial follicle to antral follicle stages (not hormone dependent) a large cohort of follicles is available at any given time to develop but most do not complete development up to that point. At the antral follicle stage which corresponds with the beginning of the menstrual cycle, a cohort of approximately 20 total follicles is present which are capable of responding to FSH and have the potential to ovulate. Only one dominant follicle of this group will be selected the others will become atretic and undergo programmed cell death. Term Are the majority of oocytes in the human never destined to develop fully or to ovulate? Definition yes Term What happens to most oocytes? Definition Most will undergo atresia due to programmed cell death at some stage of development Overall, for every oocyte that ovulates approximately 1000 will pursue abortive growth periods of variable length Term When does rate of follicular atresia become more rapid? Definition The rate of follicular atresia is not fixed and becomes more rapid approximately 10-15 years prior to menopause This correlates with a total follicle number of approximately 25,000 Term What does loss of follicles correlate with? Definition Loss of follicles has clinical correlates: Reduced odds of pregnancy Fewer follicles grow per cycle as a woman ages Menstrual cycle irregularity becomes more common Term What is the hallmark of perimenopause? Definition Menstrual irregularity with age is one of the hallmarks of the perimenopause Term What is the average age of onset of menopause? Definition Average age of onset is 46 years (39-51 in 95% of women) Term How long is the transition? Definition Average duration 5 years (2-8 years in 95% of women) Term Is abrupt cessation common? Definition Abrupt cessation of menses is unusual but may occur in up to 10% of women Term What is menopause? Definition Menopause is defined by the point in time when permanent cessation of menstruation occurs due to loss of ovarian activity Term When do most women enter menopause? Definition Median age based on cross sectional studies is between 50 and 52 years In the longitudinal Massachusetts Women’s Health Study median age was 51.3 years Fewer than 1% enter menopause at age 40 or less Term Has the age been constant? Definition Age appears to have been stable for many thousands of years Term What are the biomedical changes associated with menopause? Definition Biochemical characteristics: Elevated FSH and LH levels, low estrogen levels Term what are factors related to menopause? Definition Smoking hastens onset of menopause by 1.5 years on average (dose response), Possible familial component, Possible dietary habits (vegetarians earlier than meat eaters), Alcohol consumption might be associated with later menopause. Term what is NOT correlated with menopause? Definition No correlation with: Age of menarche; Oral contraceptive use ; Race; SES; Parity Term what is Premature Ovarian Failure? Definition Cessation of ovarian function at age 40 years or less Incidence is 1% per year Term what are the associated biochemical markers? Definition Biochemical diagnosis Elevated gonadotropins (LH, FSH) in the menopausal range need to be documented on multiple occasions at least one month apart Term can you resume functioning after POF? Definition While most effected individuals never resume ovarian function, rare cases of spontaneous pregnancies have been reported due to temporary resumption of activity Term what may cause POF? Definition Etiology: Chromosomal abnormalities; Autoimmune causes; Metabolic disorders; Infectious (mumps orchitis); Iatrogenic/Exposures; Chemotherapy; Radiation therapy Term What is Turner's Syndrome? Definition Turner’s Syndrome: Abnormality in or absence of one X chromosome resulting in ovarian failure; Most common karyotype 45X but patients can also be mosaics with two cell lines 46XX/45X; Incidence is 1/2500 to 1/5000 live born girls; Actual occurrence is higher but 99% of Turner’s conceptuses abort Term What are the clinical features of Turner's Syndrome? Definition Clinical Features: Premature ovarian failure and delayed puberty; Short stature; Renal anomalies; Cardiovascular abnormalities; Associated autoimmune disorders Term Why does TS cause POF? Definition Both X chromosomes are required to be active in the ovary to ensure normal development and maintenance of oocyte number. In Turner’s Syndrome, excessive rapid atresia of oocytes occurs starting in utero and streak gonads depleted of follicles develop Term What does TS do to the oocyte curve? Definition Oocyte curve is shifted to the left Term what are the effects of radiation TX? Definition Effects of treatment on ovarian function depends on several variables: Age of the patient at time of exposure; Treatment field, dose and fractionation schedule of radiation therapy; Type, dose and duration of chemotherapy Term What occurs with Chemo? Definition Chemotherapy: -Damage to primordial follicles occurs: --Primary target may be early granulosa cells of ovarian follicles --Abundance of multidose chemotherapy regimen makes it difficult to isolate specific drug toxicities --Alkylating agents such as cyclophsophamide are particularly damaging : ---Bind DNA, cross-linking and double strand breaks ---Not cell cycle specific and non-proliferating cells can easily be damaged Term what occurs with radiation? Definition Radiation to the pelvis is most damaging but scatter from treatment to other areas can occur: --Radiation therapy causes free radical production which results in DNA damage and cell death --Treatments are divided into fractions: ---Larger doses per fraction are associated with greater ovarian toxicity ---Extended treatment duration is also detrimental ---The LD50 of human oocytes is less than 4 Gray ---Exposure to doses greater than 6-8 Gray generally results in ovarian failure regardless of age Term What autoimmune dissease causes POF? Definition Ovarian failure has been demonstrated in patients with autoimmune disease: Type I polyglandular autoimmune syndrome ((Addison’s disease, hypoparathyroidism, chronic mucocutaneous candidiasis ) 60% risk of ovarian failure) Type II polyglandular autoimmune syndrome Addison’s disease, autoimmune thyroid disease, type I diabetes Up to 10% risk of ovarian failure Term What is the connection between autoabtibodies and POF? Definition Circulating ovarian autoantibodies are rarely positive Antibodies may be present only during a limited phase of the disease process There may be cross reactivity with autoantibodies directed at other tissues Term What should you think about with POF? Definition Infertility and fertility preservation in those treated for cancer Some women may recover ovarian function after treatment but still have compromised oocyte number and may experience difficulty conceiving For those who do not options include: Adoption In vitro fertilization with oocyte donation Embryo donation Term what fertility methods for people exposed to radiation are effective? Definition Effective: In Vitro Fertilization and embryo cryopreservation; Oophoropexy Term what fertility methods for people exposed to radiation are considered experimental? Definition Experimental: Oocyte cryopreservation; Ovarian cryopreservation and autotransplantation; Lupron administration Term Why is ovarian aging considered a physiological process? Definition Maximum accrual of follicles occurs in utero with variable rates of atresia until menopause occurs Follicular atresia is a very delicate process The determinants of the rate of follicular atresia are incompletely understood Factors that distinguish women with different ages at menopause Factors that drive accelerated follicular attrition in some women Genetic susceptibility Environmental exposures Term Is Premature ovarian failure not just an acceleration of the normal aging process? Definition yes; Several known pathologic causes have been determined some of the subtle underpinnings still to be determined