Menarche, Puberty and menstrual disorders

Question 1

what is the hypothalamic, pituitary, and ovarian axis?

Answer 1

Gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates the follicle stimulating hormone (FSH) and the lutenizing hormone (LH) from the anterior pituitary that stimulate estrogen and progesterone from the ovarian follicle

Question 2

how can the normal ovulatory cycle be divided into?

Answer 2

Follicular phase
-begins with the onset of menstruation and culminates in the preovulatory surge of LH

Luteal phase
-begins with the onset of the preovulatory LH surge and ends with the first day of menses

Question 3

what does the regressing corpus luteum mean for the ovulatory cycle?

Answer 3

Decreasing levels of estradiol and progesterone from regressing corpus luteum of the preceding cycle will initiate an increase in FSH by a negative feed back mechanism which stimulates follicular growth and estradiol secretion

Question 4

what does LH and FSH stimulate in the ovarian follicle?

Answer 4

LH stimulates:
-the theca cells to produce androgens (androstenedione and testosterone)

FSH stimulates:
-the granulosa cells to convert the androgens made by the theca cells to estrogens (E1 estrone and E2 estradiol)

Question 5

what occurs in the luteal phase?

Answer 5

Both the LH and FSH are significantly suppressed through the negative feedback effect of the elevated circulating estradiol and progesterone

If conception does not occur progesterone and estradiol levels decline near the end of the luteal phase as a result of corpus luteal regression

FSH will then rise which initiates new follicular growth for the next cycle

this always occurs 14 days after ovulation

Question 6

characteristics of Gonadotropin releasing hormone?

Answer 6

Decapeptide synthesized in the arcuate nucleus

Responsible for the synthesis and release of LH and FSH
-both LH and FSH are present in 2 different forms (releasable and storage) within the pituitary gonadotrophs

GnRH reaches the anterior pituitary and stimulates the synthesis and release of FSH and LH into the curculation

Estradiol appears to enhance the hypothalamic release of GnRH and induce the midcycle LH surge

Gonadotropins have an inhibitory effect on GnRH release

Question 7

how does estrogen levels behave in the ovarian cycle?

Answer 7

during the the follicular development estradiol levels are low

one week prior to ovulation estradiol (E2) levels begin to increase and will reach a maximium 1 day prior to the midcycle LH surge

after the peak and before ovulation there is a marked and precipitous fall

During the luteal phase, estradiol rises to a maximum 5 to 7 days after ovulation and returns back to baseline when the corpus luteum regresses

Question 8

how does progestins levels behave in the ovarian cycle

Answer 8

During the follicular development the ovary secretes only very small amounts of progesterone
-the bulk of the progesterone comes from the peripheral conversion of the adrenal pregnenolone and pregnenolone sulfate

Prior to ovulation the unruptured luteinizing graafian (mature) follicle begins to produce increasing amounts of progesterone

secretion of progesterone by the corpus luteum reaches a maximum 5-7 days after ovulation and returns to baseline before menstruation

Question 9

what is a graafian follicle?

Answer 9

it is a mature follicle in an adult ovary that is the dominant follicle

the innermost 3-4 layers of multiplying granulosa cells become cuboidal and adherent to the ovum this is known as the cumulus oophorus

A fluid filled antrum forms along the granulosa cells

• will enlarge and the centrally located primary oocyte migrates to the wall of the follicle
• innermost layer of the granulosa cells of the cumulus become elongated and form the corona rdiata
• the corona radiata is released with the oocyte at ovulation

Question 10

what does the preovulatory LH surge initiate?

Answer 10

sequence of biochemical and structural changes that result in ovulation

cells on the follicular wall surface degenerate and a stigma forms, the follicular basement membrane bulges through the stigma

when this ruptures the oocyte is expelled into the peritoneal cavity and ovulation has occured

Question 11

Function of the corpus luteum?

Answer 11

After ovulation the granulosa cells of the ruptured follicle undergo luteinization

The luteinized granulosa cells, theca cells, capillaries and connective tissue form the corpus luteum

Corpus luteum produces copious amounts of progesterone and some estradiol that functions for 9-10 days

if pregnancy does not occur, menses ensues and the corpus luteum is gradually replaced by an avascular scar called the corpus albicans

Question 12

what are the two zones of the endometrium?

Answer 12

Endometrium is responsive to circulating progestins, androgens, and estrogens

Outer portion or Functionalis:

• this layer undergoes cyclic changes in morphology during the menstrual cycle and is sloughed off at menstruation
• contains spiral arteries

Inner portion of basalis

• this layer remains relatively unchanged during each cycle and after menstruation provides stem cells for the renewal of the functionalis layer
• contains basal arteries

Question 13

endometrial changes in the menstrual cycle?

Answer 13

only portion of the cycle that is visualized externally

the first day of menstruation is known as cycle day 1

• Disruption and disintegration of the endometrial glands and stroma, leukocyte infiltration and red blood cell extravasion
• sloughing of the functionalis layer and compression of the basalis layer

Question 14

Endometrial changes in the proliferative phase

Answer 14

Characterized by endometrial growth/proliferation secondary to estrogenic stimulation

increase in the length of the spiral arteries and numerous mitoses can be seen in these tissues

Question 15

endometrial changes in the secretory phase

Answer 15

Following ovulation, progesterone secretion by the corpus luteum stimulates the glandular cells to secrete mucus, glycogen and other substances

glands become tortuous and lumen are dilated and filled with these substances

stroma becomes edematous

mitosis is rare

Spiral arteries continue to extend into superficial layer of the endometrium and become convoluted

endometrial lining reaches its maximal thickness

if conception does not occur by day 23 the corpus luteum begins to regress, secretion of progesterone and estradiol declines, and the endometrium undergoes involution

Question 16

what medications can affect the coagulation pathway that would affect menstruation?

Answer 16

Warfarin, Aspirin, Clopidogrel can impair coagulation system and be associated with heavy bleeding

Question 17

What occurs in an initial reproductive health visit?

Answer 17

occurs between the ages of 13-15 years

• important for building trust between physician and patient
• provide preventative health care services
• informational and guidance rather than problem focused

age appropriate discussion of:

• pubertal development
• normal menses
• timing of visits
• STIs
• Pregnancy prevention
• sexual orientation and gender identitiy
• rape prevention

a general exam, visual exam, and external pelvic exam may be indicated

Question 18

when is the first pap test recommended?

Answer 18

recommended by ACOG at the age of 21 years

Question 19

what is an importan vaccine that women and men should get to prevent cervical cancer?

Answer 19

at the ages of 9-26 they should look into the human papillomavirus vaccine

offers protection against cervical cancer, cervical dysplasia, vulvar or vaginal dysplasia, and genital warts associated with:

• Gardasil HPV genotypes 6,11,16, and 18
• Gardasil 9 genotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58

Question 20

when does menarche begin?

Answer 20

Median age of menarche is 12.43 years

• 10% at 11.11
• 90% at 13.75

occurs within 2-3 years after thelarche (breast budding) at tanner stage IV and is rare before tanner stage III

Question 21

what is primary amenorrhea

Answer 21

absence of menarche by age 13 years without secondary sexual development or by the age of 15 with secondary sexual development

Question 22

Cycle length and ovulation?most cycles are 21-35 days which is typical of adults

Answer 22

Menstrual cycles are often irregular throughout adolescents especially from the first to the second cycle

median first cycle is 34 days and bleed 2-7 days

Most normal cycles frange from 21-45 days even in first gynecologic year

by the third year

Question 23

Normal mestrual cycles in:
Menarche median age
mean cycle interval
menstrual cycle interval
Menstrual flow length
menstrual product use

Answer 23

Menarche median age: 12.43years
mean cycle interval: 32 days in first gynecologic year
menstrual cycle interval: typically 21-45 days
Menstrual flow length: 7 days or less
menstrual product use: 3-6 tampons per day

Question 24

what is secondary amenorrhea? and what are some possible causes

Answer 24

absence of menstruation for 6 months

it is rare for girls and adolescents to remain amenorrheic for more than 3 months
-need to rule out pregnancy

causes:

• Pregnancy
• Endocrine causes: DM, Polycystic Ovary syndrome, CD, Thyroid dysfunction, premature ovarian failure, adrenal hyperplasia
• Aquired conditions: stress related hypothalamic dysfunction, medications, exercise induced, eating disorder
• Tumors: ovarian or adrenal tumor, prolactinomas

Question 25

what is considered excessive menstrual flow?

Answer 25

Mean blood loss per menstrual period is 30cc -most report changing pad 3-6 times a day Greater than 80cc has been associated with anemia -cheanging a pad every 1-2 hours is considered excessive especially if bleeding is lasting longer than 7 days this is considered Menorrhagia or hyerpmenorrhea

Question 26

what is the PALM-COEIN classification system for abnormal bleeding?

Answer 26

PALM = structural causes: - Polyp (AUB-P) - Adenomyosis (AUB-A) - Leiomyoma (AUB-L) can be submucosal (sm) or other(o) - Malignancy and hyperplasia (AUB-M) COEIN = Nonstructural causes - Coagulopathy (AUB-C) - Ovulatory dysfunction (AUB-O) - Endometrial (AUB-E) - Iatrogenic (AUB-I) - Not yet classified (AUB-N)

Question 27

``` Abnormal bleeding definitions: Primary amenorrhea Secondary amenorrhea Polymenorrhea Metrorrhagia Menometrorrhagia Intermenstrual bleeding Oligomenorrhea ```

Answer 27

Primary amenorrhea: no menstruation has occured by the age of 13 without sceondary sexual development or by the age 15 with secondary sexual development Secondary amenorrhea: the absence of menses for 6 months or more Polymenorrhea: abnormal frequent menses at intervals less than 21 days Metrorrhagia: irregular episodes of uterine bleeding Menometrorrhagia: heavy and irregular uterine bleeding Intermenstrual bleeding: scant bleeding at ovulation for 1-2 days Oligomenorrhea: menstrual cycles greater than 35 day cycles

Question 28

What are endometrial polyps?

Answer 28

AUB-P Endometrial polyps form from endometrium to create soft friable protrusion into the endometrial cavity can cause menorrhagia and spontaneous or post menopausal bleedings may reveal focal thickening of the endometrial stripe -saline hysterosonography and hysteroscopy allows for better detection most polyps are benign but need to remove with hysteroscopy since endometrial hyperplasia and carcinoma may also present as polyps

Question 29

what are adenomyosis

Answer 29

AUB-A Defined as the extension of endometrial glands and stroma into the uterine musculature -greater than 2.5 mm beneath the basalis layer 15 percent of patients with adenomyosis have endometriosis these islands of adenomyosis do not participate in the proliferative and secretory cycles symptoms: - can be asymptomatic - severe secondary dysmenorrhea and menorrhagia - can be associated with dyspareunia with deep penetration

Question 30

what are uterine Leiomyomas?

Answer 30

AUB-L also known as fibroids Benign tumors derived from smooth muscle cells of the myometrium - most common neoplasm of the uterus - greater than 45% of women in 5th decade will have them - rarely malignant - most are asymptomatic Symptoms fibrinoids can cause: - excessive uterine bleeding, pelvic pressure, pelvic pain, and infertillity - most common indication for a hysterectomy Risk factors for developing fibroids: - increasing age - African american at higher risk - nulliparity - family history

Question 31

what are possible locations of fibroids?

Answer 31

submucosal at the side of the uterus intersitial in myometrium subserosal at top of uterus cervical in the cervix

Question 32

Characteristics and symptoms of Leiomyomas

Answer 32

Fibroids AUB-L rarely form before menarche or enlarge after menopause - estrogen stimulates the proliferation of smooth mm cells - enlarges during pregnancy Usually spherical, well circumscribed, white firm lesions with a whorled apperance on cut sections may cause pain and degenerate and may calcify in post menopausal patients Symptoms: - most asymptomatic - pelvic or lower back pain - frequent urination - severe pain not common unless inflammed - prolonged or heavy bleeding - increased incidence of infertillity

Question 33

what is endometrial hyperplasia? and the 2 types

Answer 33

AUB-M Represents an overabundance growth of the endometrial lining usually as a result of persistent unopposed estrogens - PCOS - Granulosa theca cell tumors (estrogen producing) - Obesity via peripheral conversion of androgens to estrogens via fat cells - exogenous estrogens without progestins - Tamoxifen precursor to endometrial cancer Hyperplasia: - simple without atypia - complex without atypia - simple with atypia - complex with atypia can be type 1 = endometrial adenocarcinoma type 2 = clear cell and papillary serous presentation: - Postmenopause bleeding is most common] - irregular uterine bleeding during premenopause

Question 34

Coagulopathies

Answer 34

AUB-C associated with heavy flow -Von willebrand disease

Question 35

Ovulatory dysfunction

Answer 35

AUB-O Associated with unpredictable menses with variable flow -polycystic ovarian syndrome

Question 36

Endometrial causes

Answer 36

AUB-E infection

Question 37

Iatrogenic

Answer 37

AUB-I IUD, IUS, exogenous hormones

Question 38

Not yet classified abnormal uterine bleeding

Answer 38

AUB-N reserved for entities that are poorly defined and or not well examined -arteriovenous malformation

Question 39

what are some laboratory and available diagnostic tests to run when evaluating abnormal uterine bleeding?

Answer 39

Labratory tests: - Pregnancy test - CBC - Targeted screening for bleeding disorder (PT, PTT) - TSH - Chlymadia trachomatis Diagnostic or imaging tests - transvaginal ultrasonography - saline infusion sonography - MRI - Hysteroscopy

Question 40

Indications for a in office endometrial biopsy and contradictions

Answer 40

Abnormal uterine bleeding - postmenopausal women that have spotting or bleeding or have endometrial lining greater than 4 mm - age 45 to menopause that have any AUB - less than 45: any bleeding that occurs in the setting of unopposed estrogen exposure Cervical cytology results indicated positive glandular cells on cervical cytology Contradictions: - absolute pregnancy - relative bleeding diathesis

Question 41

what are AUB treatments with medication?

Answer 41

Normalize prostaglandins -NSAIDS prior to and during menses Antifibrinolytic therapy -tranexamic acid Coordinate endometrial sloughing - Medoroxyprogesterone MPA - Combined oral contraceptives Endometrial suppression: - Progesterone daily - continuous OCP - intrauterine system

Question 42

AUB treatment with surgical options

Answer 42

``` Polypectomy Myomectomy Dilation and currettage uterine endometrial ablation hystorectomy ```

Question 43

Diagnostic and suction D and C

Answer 43

Dilation and Currettage Diagnostic D and C: -performed for irregular menstrual bleeding or postmenopausal bleeding to rule out endometrial hyperplasia or cancer Therapeutic D and C -performed for endometrial structural abnormalities (Polyps, small pedunculated submucosal fibroids)

Question 44

Endometrial ablation

Answer 44

Uses radiofrequency to the bupolar mesh electrode while at the same time applying suction perforation safety mechanism ablation time 90 seconds

Question 45

What are the 4 different routes for Historectomys?

Answer 45

Total abdominal hysterectomy (TAH) -incision above the abdomen ``` Vaginal hysterectomy (TVH) -vaginal incision ``` Laparoscopic assisted vaginal hysterectomy (LAVH) -small abdominal incisions and vaginal incisions da Vinci assisted hysterectomy: -small abdominal incisions and vaginal incisions

Question 46

when is puberty, how long is it, and what are some factors affecting when it starts?

Answer 46

Encompasses the development of secondary sexual characteristics and the acquisition of reproductive capabillity duration is 4-5 years Usually occurs between 10-16 years old and mean is 12 onset determined by: - genetic factors (hispanic and AA girls earlier - geographic location (metropolitian or at altitudes/sea level earlier) - Nutrition (obese have earlier, malnourished is later)

Question 47

how does childhood keep pubery suppressed

Answer 47

HPO is suppressed between ages of 4-10 years low levels of gonadotropins and sex steroids during prepubertal period are due to 2 functions: - gonadostat sensitivity to the negative feedback of low circulating estradiol - intrinsic central nervous system inhibition of the hypothalamic gonadotropin releasing hormone (GnRH)

Question 48

what occurs in late childhood that leads to start of puberty?

Answer 48

between ages of 8-11 there is an increase in serum concentrations of dehydroepiandrosterone (DHEA and dehydroepiandrosterone sulfate (DHEA-S) and androstenedione rise in adrenal androgens causes growth of axillary and pubic hair at age 11 -gradual loss of sensitivity by the gonadostat to the negative feedback of sex steroids and loss of inhibition of GnRH these increase in GnRH lead to production of ovarian follicular maturation and sex steroid production to develop the secondary sexual characteristics by late puberty the positive feedback mechanism of estradiol on LH release from the anterior pituitary gland is complete and ovulatory cycles are established

Question 49

what are the stages of normal pubertal development?

Answer 49

Thelarche (breast development - first sign of puberty - unilateral development and tenderness in first 6 months not uncommon - requires estrogen Pubarche/adrenarche - pubic hair and axillary hair development - requires androgens Maximal growth or peak height velocity - occurs 2 years earlier in girls - occurs 1 year before menses Menarche - onset of menses - requires pulsatile GnRH, FSH, and LH from pituitary, estrogen and progesterone from ovaries

Question 50

5 stages of Tanner staging for breast development

Answer 50

Stage 1: preadolescent elevation of the papilla only stage 2: breast bud stage; elevation of the breast and papilla as a small mound with enlargement of the areolar region stage 3: furthur enlargement of breast and areola without separation of their contours stage 4: projection of areola and papilla to form a secondary mound above the level of the breast stage 5: mature stage; projection of papilla only resulting from recession of the areola to the general contour of the breast

Question 51

5 stages of Tanner staging for pubic hair

Answer 51

Stage 1: preadolescent absence of pubic hair stage 2: sparse hair along the labia; hair downy with slight pigment stage 3: hair spreads sparsely over the junction of the pubes; hair is darker and coarser stage 4: adult type hair; there is no spread to the medial surface of the thighs stage 5: Adult type hair with spread to the medial thighs assuming an inverted triangle pattern