Reproduction L06 Menstrual_Cycle

Front 1

What is polymenorrhea?

Back 1

Polymenorrhea: menstrual interval of less than 21 days

Front 2

What is the median age of menopause?

Back 2

51.3 years old

Front 3

At what age is end of menses considered ovarian failure NOT menopause?

Back 3

≤ 40 y/o

Front 4

What can cause menstrual disorders?

Back 4

Menstrual disorder can arise from any disturbance in the body systems… usually they act by influencing GnRH episodic secretion

Front 5

T/F: adrenal steroids and prolactin can cause menstrual disorders

Back 5

True, both adrenal steroids and prolactin can cause menstrual disorders

Front 6

What is the first step in ruling out menstrual disorders?

Back 6

first rule out pregnancy in diagnosing menstrual disorder

Front 7

Which two age groups do you often see menstrual abnormalities?

Back 7

Menstrual abnormalities at: early ost pubertal and within 5 years of menopause

Front 8

what is the cause of menstrual abnormalites during Early Post Pubertal age?

Back 8

First two years of puberty: Due to hypothalamic immaturity menstuation occurs at irregular intervals (2-12 months apart) and may take several years to establish regular intervals

Front 9

what is the cause of menstrual abnormalites within 5 years of menopause??

Back 9

within 5 years of menopause: failing ovarian follicular apparatus --> menstual abnormalities

Front 10

When should one check for abnormalities in a women 20-40 years old?

Back 10

evaluate menstrual abnormalites lasting longer than 6 months in women 20-40 y/o

Front 11

What are the 5 major (common) causes of menstrual abnormalities?

Back 11

5 major catagories of causes of Menstrual Abnormalities: (1) Energy related, (2) Outside environmental/psychologic influences, (3) Medical illness, (4) Pituitary-Ovarian Axis, (5) Hormonal Inferences

Front 12

Whatt are the 4 subcatagories of energy related menstrual abnormalities?

Back 12

Energy Related Menstrual Abnormalities: (1) Weight loss (2) Anorexia, (3) Obesity, (4) Exercise

Front 13

What happens during anorexia?

Back 13

resumption of dirunal variation of gonadortopins and with further weight loss a decrease in gonadotropins to prepubertal levels

Front 14

What effects can obesity have on Menstruation?

Back 14

Obesity can cause oligomenorrhea or amenorrhea

Front 15

What 3 clincial finding are seen with obesity-caused amenorrhea?

Back 15

Obesity-amenorrhea clinical finding: (1) i. Low or low normal goadotropin levels (2) Short luteal phase w/ infertility (3) ↑ hirsutism (male pattern baldness) w/ PCOS-like picture

Front 16

What is the etiology behind Exercise-induced amenorrhea?

Back 16

"Exercise related amenorrhea: (1) Energy requirements OR (2) excess ß endorphins → ↓ GnRH production

Front 17

What types of menstrual abnormalities are seen with Outside Environment or Psychologic Influences?

Back 17

Amenorrhea or oligomenorrhea are seen with Outside Environment or Psychologic Influences.

Front 18

What is the mechanism by which B. Outside Environment or Psychologic Influences occurs?

Back 18

Outside Environment or Psychologic Influences --> Hypothalamic Amenorrhea: where CNS input has an effect on the hypothalamic centers controlling GnRH… (perhaps due to a change in sensitivity to negative feedback)

Front 19

In Outside Environment or Psychologic Influences caused amenorrhea/oligomenorrhea, what are the levels of LH, FSH, Androgens, and prolactin?

Back 19

In Outside Environment or Psychologic Influences caused amenorrhea/oligomenorrhea, the levels of LH, FSH, Androgens, and prolactin are all NORMAL

Front 20

What effect do TB and DM have on menstruation?

Back 20

TB and DM both can cause amenorrhea

Front 21

What is the mechanism by which DM causes amenorrhea?

Back 21

Pathogenesis of amenorrhea in DM: DM → Hypoglycemia intracelluarly in adrenals →Excess androgens → amenorrhea

Front 22

How can you correct DM-related amenorrhea?

Back 22

Correction of hyperglycemia is corrective of DM-related amenorrhea

Front 23

Which 3 types of menstruation abnormalities are associated with Iron Deficiency Anemia? What is the Rx?

Back 23

Menstruation abnormalities associated with Iron Deficiency Anemia: Anovulation, Menorrhagia, Amenorrhea… Rx: iron supplements

Front 24

What type of menstruation abnormality is associated with hepatic failure? Why?

Back 24

Hepatic failure --> low gonadotropin production --> amenorrhea

Front 25

What 3 things can cause amenorrhea that are associated with the Pituitary-ovarian axis?

Back 25

These 3 pituritary-ovarian axis dysfunction can cause amenorrhea: (1) Pituitary tumor (craniopharyngioma) w/ low LH/FSH, (2) decreased TSH release, and (3) porlactinomas

Front 26

What is the etiology behind LH-FSH destroying pituitary lesion that cause amenorrhea?

Back 26

The etiology behind LH-FSH destroying pituitary lesion that cause amenorrhea = LOW GONADOTROPIN AMENORRHEA

Front 27

What is the etiology behind prolacitmeas that cause amenorrhea?

Back 27

The etiology behind prolacitmeas that cause amenorrhea is = ↑ PRL → GnRH shut off (not compression or destruction of pituitary)

Front 28

What is the treatment of prolactinoma induced amenorrhea? What should be measured with every case amenorrhea? What should be ruled out when an increase in prolacin is seen?

Back 28

(1) What is the treatment of prolactinoma induced amenorrhea? Dopamine agonist - "bromocriptine" (2) What should be measured with every case amenorrhea? Prolactin… (3) What should be ruled out when an increase in prolacin is seen? Pregnancy

Front 29

At what age are ovarian related amenorrhea seen?

Back 29

> 40 y/o

Front 30

When do you see ovarian related causes of amenorrhea in young people?

Back 30

When do you see ovarian related causes of amenorrhea in young people? Due to genetic or autoimmune disorder that lead to amenorrhea

Front 31

How do you diagnose ovarian related amenorrhea? What is the Rx for ovarian related amenorrhea?

Back 31

A diagnosis of ovarian related amenorrhea is made with ↑ FSH (> 40 IU/L)… (2) Rx: replace missing hormones: E2 and progesterone

Front 32

What 2 types of mensturation abnormality are related to the uterus?

Back 32

Uterus: Primary amenorrhea (absence) and disease related amenorrhea

Front 33

Which diseass associated with amenorrhea are seen in the uterus?

Back 33

Which diseass associated with amenorrhea are seen in the uterus? SCAR TISSUE and INFECTION (e.g., TB of the uterus)

Front 34

How do you diagnose uterus related amenorrhea?

Back 34

How do you diagnose uterus related amenorrhea? Administer E and Progesteron: if slouging occurs --> normal… If no bleeding --> abnormal

Front 35

What is PCOS caused by?

Back 35

PCOS is caused by excess steroidal secretion by the ovaries or the adrenal glands.

Front 36

What is the effect of excess steroid production in the ovaries or adrenal glands?

Back 36

What is the effect of excess steroid production in the ovaries or adrenal glands? Both have a Neg FB effect on the HP axis… e.g., estrogen excess by the adrenals would effect the entire cycle.

Front 37

Give and example of the effects of (1) E production by the adrenals and (2) androgens made by the ovaries or adrenals in menstrual abnormalities.

Back 37

"Give and example of the effects of (1) E production by the adrenals --> estrogen excess by the adrenals would effect the entire cycle…. (2) androgens made by the ovaries or adrenals in menstrual abnormalities.e. Androgens made by ovaries or adrenal --> A→ E in fat cells → E results in cycle abnormalities

Front 38

What effect does prolactin have on gonadotropins?

Back 38

Elevate PRL interferes with gonadotropins

Front 39

What is the normal range of menstrual cycle? Days of bleeding? Age of onset of menarch?

Back 39

What is the normal range of menstrual cycle? 21-35 days…(2) Days of bleeding? 5-7 days… (3) Age of onset of menarch? 9-18 y/o

Front 40

What effect do CRH, opioids and dopamine have on the pulse generator?

Back 40

What effect do CRH, opioids and dopamine have on the pulse generator? INHIBITORY effect on the pulse generator

Front 41

what is the etiologic effect of TSH and prolactin on the release of FSH and LH from the pituitary?

Back 41

what is the etiologic effect of TSH and prolactin on the release of FSH and LH from the pituitary? inhibition of the GnRH pulse

Front 42

Ignore

Back 42

Ignore

Front 43

Scenarario: [A 21 y/o girls w/ no onset of menses, no major illness, no extreme exercise, no drug use. She's 5'8" with little axillary hair… her Tanner stages: Breasts=1… pubic hair=4… small uterus and normal gonads] Labs: [T3 normal, PRL normal, FSH/LH low, E2 low, Androgens normal, normal (yet prepubertal) uterus, normal ovaries] GIVE A DIAGNOSIS

Back 43

Hypothalamic Amenorrhea… aka, special case of Hypogonadotropic hypogonadims

Front 44

What is the general etiology of Hypothalamic amenorrhea?

Back 44

(1) Too few GnRH pulses, (2) OR -Extreme example: Kallmann's syndrome

Front 45

What is the mechanism of Kallmann's syndrome-induced hypothalamic amenorrhea? (5 items… hint genetic)

Back 45

(1) Congenital, (2) no GnRH neurons in hypothalamus, (3) associated w/ anosmia/hyposmia, (4) absent olfactory sulci in rhinencephalon (failure of olfactory and GnRH neuronal migraiont from olfactory placoid in nose), (5) X-linked --> kal1--> anosmin

Front 46

What is the Rx for Hypothalamic amenorrhea? And the effect of the Rx?

Back 46

Rx: estrogen and progesterone --> breast dev, stops growth, maintain bone density, increases uterine size, stimulates endometrium (menses)

Front 47

How do you induce ovulation in hypothalamic amenorrhea?

Back 47

(1) GnRH pump, (2) exogenous FSH/LH

Front 48

"NARROW THIS DOWN: Anorexia nervosa–Chronic illness–Constitutional delay– Endocrinopathies–-Cushing’s syndrome–-DM-GH deficiency–-Hyperprolactemia–

Back 48

"NARROW THIS DOWN: Anorexia nervosa–Chronic illness–Constitutional delay– Endocrinopathies–-Cushing’s syndrome–-DM-GH deficiency–-Hyperprolactemia–

Front 49

What are the 6 key points of Hypothalamic amenorrhea?

Back 49

(1) low or normal gonadotropins (FSH/LH) (2) Low E, (3) normal karyotype, (4) absent GnRH pulse, (5) often associated w/ stress, eating, exercise, (6) ovaries still function

Front 50

SCENARIO: [ 18 y/o girl with no onset of menses, ht=4'7", some axillary hair, tanner: breast 1, pubic hair2, Pelvis: small uterus, gonads not palpable, web neck, low hairline, high arched palate, cubitis valgus, shield chest, short 4th metacarpel.] LABS: high FSH/LH, low estrodiol, androgens normal, no gonads w/ normal uterus] GIVE DIAGNOSIS

Back 50

Hypergodanotropic hypogonadism

Front 51

What are the eitiologies of hypergondotropin hypogonadism?

Back 51

"Idiopathic - Autoimmune - Galactosemia - Gonadal agenesis/dysgenesis - Genetic - “Resistant ovaries” - Chemotherapy (eg: alkylating agents) - Radiation (>800 rads, >15 years old) - Infection (mumps) - Surgery - Sickle cell disease - Trauma - StAR defect (congenital lipoid adrenal hyperplasia)[ p450c17, 17-ketosteroid, reductase]

Front 52

What is the kayrotype of Turners syndrome?

Back 52

45 X

Front 53

What disorders are associated with Turner's syndrome?

Back 53

renal, hearing, autoimune (10% hypothryroidism), CV (bicuspid aortic valve, coarctation of aorta, arotic aneurisms

Front 54

What is the Rx for Turner's syndrome?

Back 54

(2) Provide Estrogen/progesterone for breast dev, maintain bone density, increase uterus size, stimulate endometrium. (2) Fertility: Egg donation, adoption

Front 55

What are the 4 key points of hypergonadotropic hypogonadism?

Back 55

(1) high FSH/LH (2) low estrogen, (3) often abnormal karyotype, (4) Ovarian failure (no more eggs, no hormone production)

Front 56

SCENARIO: [25 y/o girl w/ irregular menses and exces hair growht , no major medical problems, menarche at age 11, with onset of abdominal and facil hair, menses every 2-4 months w/ last period 4 months ago]PE: [ Normal height, hirsuit, normal ovaries and uterus], FAMILY Hx: [ father DM, mother hirsuitims], LABS:[high androgens (T, androstenedione, DHEA, DHEAS 17-hydroxyprogesterone, LH:FSH=3:1 ratio, low progesterone (0.5 ng/mL), Basal body temp chart (monophasic/anovulatory)... ultrasound = multiple peripheral cysts] GIVE DIAGNOSIS

Back 56

Hypergonadotropic hypogonadism --> w/ multiple cysts -->hyperandrogenic Anovulation (aka, PCOS)

Front 57

Which 5 hormonal factors affect hypothalmic-pituitary-ovarian axis in PCOS?

Back 57

(1) androgens converted to estrogens in fat (2) more fat --> more conversion, (3) increased estroge --> increased LH, (4) increased LH --> increased ovarian androgens… cycles

Front 58

what role does insulinemia play in increased androgens?

Back 58

insulin increase --> increaed LH --> increased ovarian androgens

Front 59

What is SHBG? And what does a drop in SHBG cause?

Back 59

SHGB: sex hormone binding protein (for androgens)… a decrease in SHBG causes in increase in androgens

Front 60

What is the primary effect of FSH in the menstrual cycle

Back 60

FSH (mainly) → ↑ follicle growth

Front 61

What is the primary effect of LH in the menstrual cycle

Back 61

LH (mainly) → ↑ gonadal steroid synth

Front 62

What are the three main components in regulating follicular development and ovulation?

Back 62

gonadotrophins + E2 + progesterone --> associated with follicular development and ovulation

Front 63

What is the Pituitary Tubero-infindublular Neuron System?

Back 63

Blood supply… components: median eminence --> and hypothalamic-pituitary portal system

Front 64

What regulates feedback control of GnRH?

Back 64

E2 and progesterone plasma concentration… FB control

Front 65

When is LH and FSH released in greatest quantity?

Back 65

LH and FSH are released in high quantity during EARLY FOLLICULAR PHASE

Front 66

What causes the release of LH and FSH during the Early Follicular Phase

Back 66

↓E2 &↓P → GnRH → LH & FSH release

Front 67

What happens to FSH and LH levels in the Mid-Late Folicular Phase? (2) Give the mechanism for this.

Back 67

FSH: Maturing follicles → ↑ E2 → ↓ FSH… (b) Pre-ovulatory surge in (↑)E2 → ↑ LH (⊕ FB response)

Front 68

What two things arise out of the Mid-Late Follicular phase increase in LH?

Back 68

Pre-ovulatory surge in (↑)E2 → ↑ LH (⊕ FB response) --> OVULATION and CORPUS LUTEUM FUNCTION

Front 69

What happens during post ovulation & Dev of Corpus Luteum (w/o pregnancy)

Back 69

During post ovulation & Dev of Corpus Luteum (w/o pregnancy)… ↑ E2 + ↑ P→ ↓ FSH ↓LH

Front 70

Which 2 things regulates the hypothalamus-pituitary release of GnRH?

Back 70

CNS and STEROID HORMONE RELEASE

Front 71

What is behind the mechanism of the dysfunctionally constant GnRH release?

Back 71

Constant GnRH --> Internalization of GnRH-® on pituitary → Complete absence of LH & FSH→ No follicle development→ No Steroid Hormone Synthesis

Front 72

Where is the LHRH (GnRH) pulse generation initiated?

Back 72

Arcuate Nucleus (AN): Location of Pulse Generation

Front 73

What are the effects of NE and Dopamine at the Acruate Nucleus of the hypothalamus?

Back 73

Dopamine @ AN → ↓ GnRH pulse activity AND NE @ AN → ↑ GnRH pulse activity

Front 74

What effect do dopamine and NE have on the GnRH pulse frequency?

What are Dopamine and LH modified by?

Back 74

What effect do dopamine and NE have on the GnRH pulse frequency?

NE --> stimulate
Dopamine --> inhibits

Both Dopamine & NE are modulated by ß endorphins and catecholestrogens

Front 75

Give the pathway for the Ultra-short, short, and long loops.

Back 75

Long Loop FB: E2 and P → ↓ GnRH… Short Loop FB: ↑FSH ↑LH → ↓ GnRH… Ultrashort Loop FB: ↑↑ GnRH → ↓ GnRH (autoregulation)

Front 76

Which pituitary cells relesae LH and FSH?

Back 76

Basal Chromophobic Gonadotropin cells → LH & FS

Front 77

What modifies the release of LH and FSH?

Back 77

LH and FSH release is modified by E2 and progesterone

Front 78

T/F: FSH and LH are amino acids with alpha specificity

Back 78

False: FSH and LH are glycoproteins, with common ∂ subunit and ß specificity

Front 79

What are the 2 functioning pools of pituitary gonadotropins? What is the "functionl capacity"?

Back 79

(1) (a) acutely releasable: LH & FSH (b) reserve: releasable after repeated GnRH stimulation… (2) Functional capacity: Acute pool + reserve

Front 80

When during the menstrual cycle do you see negative feedback? And when do you see positive feedback?

Back 80

Negative FB: follicular & Luteal phases… Positive FB: pre-ovulation E2 surge.

Front 81

What causes Negative FB and which gonadotrophin is being inhibited?

Back 81

Neg FB: In follicular and luteal phases Progesterone and E2 inhibit FSH and LH

Front 82

What causes Positive and which gonadotrophin is being stimulated?

Back 82

Pos FB: During Pre-ovulation a surge ↑↑↑E2 above threshold → ↑LH

Front 83

During the onset of menstration what effect does decreased E2 have on FSH?

Back 83

Onset of Menstration: ↓ E2 → ↑ FSH

Front 84

In the second half of follicular phase, what effect on FSH does a surge in E2 have?

Back 84

Second half of follicular phase: ↑↑ E2 → ↓ FSH

Front 85

When is the rate of follicular release greater, follicular or luteal phse?

Back 85

follicular phase pulse = 1/60-90 min… luteal phase pulse = 1/100-160 min

Front 86

What are the two functions of the ovaries?

Back 86

Gametogenesis and steroidgenesis

Front 87

What is synthesized during steroidogenesis?

Back 87

E2, progesterone, and androstenedione

Front 88

In gametogenesis: what must mature for ovulation to occur?

Back 88

Gametogenesis: Maturation of follicles → ovulation

Front 89

Give the pathway and location for the secretion of androgens.

Back 89

Androgens made in theca cells: (2) In theca cells: LH → Induces enzyme @ theca cells → causes the conversion of Cholesterol → to androstenedione & T

* note: stroma cells are precursors to theca cells

Front 90

Give the pathway and location for the secretion of estradiol.

Back 90

(1) Gramulosa Cells → Secrete E2: (2) In Granulosa cells: (b) FSH → induction of enzyme @ granulosa cells: Androstenedione → estrone… (b): FSH induces T → E2 (aromatization)

Front 91

What 3 effect does E2 have on granulosa cells?

Back 91

↑ E2 by granulosa cells --> (1) ↑ FSH-® on granulosa cells (2) Granulosa cell mitosis creating more granulosa cells (3) ↑ Follicular fluid E2... thus E2 sort of positively feeds back

Front 92

Where is progesterone made?

Back 92

Corpus luteum is where progesterone is made

Front 93

At what time (in days) during the menstrual cycle is the dominant follicle selected from its cohort and what is the mechanism?

Back 93

Time: Day 5-7 of M-cycle… (2) Dominant follicle selected from cohort Mechanism: ↑ FSH-® on dominant follicle → thus ↑ FSH stimulation on dominant follicle

Front 94

In terms of the granulosa cells, what is the difference between the Primordial follicle and the Primary follicle?

Back 94

Primordial follicle has 1-layer of granulosa cells… the Primary follicle has multiple layers of granulosa cells.

Front 95

where on the follicle do you find theca cells, what differentiate into theca cells?

Back 95

Stroma of the ovary differentiates into → theca cells surround the follicle

Front 96

What causes the LH surge and what results from this. What is the time frame?

Back 96

(1) Serum [↑↑↑↑E2 ] + progesterone → LH surge (2) LH surge results from ⊕ FB of ↑↑↑E2 @ pituitary (3) LH surge –(36 hours later..)→ Ovulation (~16 hr span after LH peak????)

Front 97

What causes the follicle rupture leading to the release of the ovum?

Back 97

↑PGE-2 + proteolytic enzymes + plasminogen activator → follicle rupture

Front 98

When is the corpus luteum formed (2) what is converted to the corpus luteum? (3) What is involved in the conversion?

Back 98

(1) When is the corpus luteum formed: Follows extrusion of ovum (2) what is converted to the corpus luteum? 2. Granulosa cells → undergo luteinization … (3) What is involved in the conversion? Vascularization and progesterone production begins

Front 99

What finally produces a negative feedback on LH?

Back 99

Due to continued LH stimulation →↑ progesterone (midluteal) @ corpus luteum → now Combined E2 & P production in serum →↓FSH ↓LH @ pituitary

Front 100

What the 2-possible outcomes for the corpus luteum?

Back 100

(1) Luteolysis: degeneration & lysis (2) Pregnancy: hCG from trophoblasts → Corpus Luteum stimulation → production of P for first 7-8 weeks of pregnancy

Front 101

Match the following definition to the disorder (primary amenorrhea, secondary amenorrhea, oligomenorrhea, hypomenorrhea, menorrhagia, metroorrhagia): menses occurs 2 months apart/ or greater than 35 days - more than once…

Back 101

Oligomenorrhea: menses occur 2 months apart / or greater than 35 days (more than once)

Front 102

Match the following definition to the disorder (primary amenorrhea, secondary amenorrhea, oligomenorrhea, hypomenorrhea, menorrhagia, metroorrhagia): decreased blood flow during menses

Back 102

Hypomenorrhea: decreased blood flow during menses

Front 103

Match the following definition to the disorder (primary amenorrhea, secondary amenorrhea, oligomenorrhea, hypomenorrhea, menorrhagia, metroorrhagia): absense of menses, previously had

Back 103

Secondary Amenorrhea: absense of menses, previously had

Front 104

Match the following definition to the disorder (primary amenorrhea, secondary amenorrhea, oligomenorrhea, hypomenorrhea, menorrhagia, metroorrhagia): bleeding in between – out of normal times, w/ irregular intervals

Back 104

Metrorrhagia: bleeding in between – out of normal times… w/ irregular intervals

Front 105

Match the following definition to the disorder (primary amenorrhea, secondary amenorrhea, oligomenorrhea, hypomenorrhea, menorrhagia, metroorrhagia): absence of mense ever

Back 105

Primary Amenorrhea: absence of mense ever

Front 106

Match the following definition to the disorder (primary amenorrhea, secondary amenorrhea, oligomenorrhea, hypomenorrhea, menorrhagia, metroorrhagia): excess flow at mensus w/ normal interval

Back 106

Menorrhagia: excess flow at mensus w/ normal interval

Front 107

How do you diagnose primary and secondary amenorrhea?

Back 107

Primary Amenorrhea: a) no menses by 14 w/o evidence of secondary sexual characteristics… b) non menses by 16 w/ evidence of sexual characteristics… (2) Secondary Amenorrhea: no menses for 3-6 months

Front 108

What are the etiologies of Hypothalamic Amenorrhea

Back 108

NARROW THIS DOWN:

Front 109

What is plymenorrhea?

Back 109

Polymenorrhea: menstrual interval of less than 21 days