Hypothalamic pituitary

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Adrenal

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Ovarian

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Uterine outflow tract

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Menstruation

When does menarche typically occur?

When does perimenopause occur?

When does menarche typically occur? 12.4

When does perimenopause occur? 51.4

·   Interrupted  by pregnancy, lactation, illness, birth control pills, gynecologic disorders, exogenous factors, any mechanism containing hormones

3 components

1.       Beginning: Menstruation and follicular phase

2.       Ovulation: release of egg

3.       Luteal phase: under influence of corpus luteum

What phase does this describe:

begins on the day of the LH surge and ends with the onset of menses

Take number of days of cycle-14=when they ovulate

23-14=Day 9

30 day cycle- when do you ovulate?

30-14= ovulate around day 16

What are hormones?

Are all hormones the same?

·   Hormones are substances produced in a special tissue, where it is released into the bloodstream, and travels to distant responsive cells in which the hormone exerts its characteristic effects

·   Hormones can be viewed as chemical regulatory and signaling agents

All hormones are NOT the same

What is

HYPOTHALAMIC PITUITARY-OVARIAN AXIS?

What is released by each area?

•       Refers to the interactions between the hypothalamus, pituitary, and ovaries that regulate the reproductive cycle

Hypothalamic: GnRH

Pituitary: FSH and LH

Ovaries: Estrogen and progesterone

hypothalamus is a pulse generator (like the heart; called the arcuate nucleus; this reaches pituitary via blood and releases FSH and LH; CANNOT MEASURE GnRH because in the middle of the brain, but we CAN measure LH

NOPE

have to measure LH and FSH to check the function of the hypothalamus

Who does the hypothalamus "talk"directly to?

how do they talk (whats the means?)

ANT pituitary

via the hypo-thalamic-pituitary portal vascular system

·   Ovarian function requires the pulsatile secretion of GnRH in a specific pattern ranging from 60 minutes to 4 hours

·   Because of the location of its release and very short life of only 2-4 minutes,  direct measurement of GnRH secretion is not possible, instead measurement of LH  pulses are used to indicate GnRH pulsatile secretion

low estrogen causes _________ feedback

steady estrogen causes __________ feedback

low estrogen causes positive feedback

steady estrogen causes negative feedback

Steady state of estrogen; sending neg inhibition to brain

Follicle: basement membrane is a barrier, inside granulose, stroma has cells called theca cells; under right stimulus granulose cells produce estrogen; outer cells in stroma or theca produces androgens. Ovary doesn’t want androgens bc with enough androgens we stop ovulation; OVARY WANTS ESTROGEN! Lets do something so androgens can cross basement membrane and get into granulose and add chemicals and convert androgens to chemicals= called two cell theory of estrogen production in the follicular cell of ovary

LH causes androgens to cross basement membrane where it converts to androstendione to estrogen and goes to blood

glycoproteins

secreted by ant pituitary

•       Magnitude and rates of secretion are determined by the levels of ovarian hormones estrogen and progesterone and other factors such as inhibin and activin 

What is the role of activin? Who does it work on?

What does it inhibit?

enhances production of FSH

And inhibits release of prolactin; increases FSH binding/ activates cycle and tries to get everything going; increases receptors, increases FSH; plays a role in changing two cell process

Inhibin: inhibits FSH and GnRH from the start; the more FSH, the more FSH~no effect on LH

Estrogen is going up and FSH is stimulating follicle; everything is going nice, estrogen is growing, why inhibin? Why inhibit FSH? Bc only want one egg! If not, if everyone was getting stimulated you would litters

Inhibin is the way to put body in check

two cell theory:

•   Immature follicle is encircled by a single layer of _______followed by a thin basement membrane that separates the follicle form the the surrounding stroma

•   Stroma cells differentiate into _____

•   Granulosa cells produce _______, including________ and _______

•   Theca cells produce _______which serve as the precursors required for granulosa cell estrogen production.

•   ________enter the granulosa cells by diffusion and are converted to estrogen.

•   Immature follicle is encircled by a single layer of granulosa cells followed by a thin basement membrane that separates the follicle form the the surrounding stroma

•   Stroma cells differentiate into theca cells

•   Granulosa cells produce estrogens, including estrone and estradiol

•   Theca cells produce androgens which serve as the precursors required for granulosa cell estrogen production.

•   Androgens (androstenedione and testosterone) enter the granulosa cells by diffusion and are converted to estrogen.

LH stimulates theca cells to produce __________

What is this process called:

Increased androgen production leads to increased estrogen production

Who makes activin?

what does it increase? what does it inhibit?

gonads and pituitary

increases FSh

inhibits prolactin

True or False

Activin participates in androgen synthesis, enhancing LH action in the ovary.

What does this describe?

 Inhibits FSH production and GnRH release from the hypothalamus

True or false.

Inhibin inhibits both FSH and LH

FALSE

no effect on LH

ovulation

•  Ovulation results in the dominant ovarian follicle releasing its oocyte and transitions to a progesterone-secreting ovarian cyst, the corpus luteum

Rising estrogen; estradiol (dominant estrogen); instead of having inhibitory action it turns to pos action-if it goes up quickly or above 400 picograms goes into stimulatory effect and tells brain to push forward so you get more estrogen AND get midcyle surge of LH- this causes follicle to pop! Activates prostaglandins CALLED OVULATION!

progesterone

follicle changes names and becomes corpus luteum and starts making an additional hormone called progesterone (estrogen is still made)

•  LH surge _______ ovulation by 34-36 hours

•  Mid-cycle LH surge  stimulates these receptors and converts enzymatic machinery of these cells to produce progesterone, this process is called luteinization

•  Corpus luteum also produces _________ in pattern that parallels progesterone production

Life expectancy of corpus luteum is 11 days; reason why second half of cycle is about 14 days. If conception does not occur- corpus luteum breaks down bc progesterone drops sharply; as progesterone starts to fall, inhibin starts to go down too; so what happens? Lose negative feedback—so FSH which has been suppressed/menstruation has not begun, but FSH starts to rise; if conception does not occur during 10 days; as progesterone starts to fall, so take away inhibitory mechanism and get machine to work again; turn off inhibin and get activin going and turn on FSH to get ready for another cycle and pick another follicle.

releases FSH from negative feedback

•  FSH begins to rise before menstruation

How do you know if ovulatory or anvoulatory?

Period: Non clotting blood and contain endometrium tissue- sloughing epithelial layer of tissue 

PGs cause spasm/contracture of muscles and causes ischemia 

Cramping: as progesterone is dropping- PGs are released, endometrium getting ischemic this is prodromal cramping preceding menstruation 

Day 1 of period: estradiol starts to rise; estrogen In early follicular phase, reason bleeding stops bc estrogen has healing effect to bleeding

menstruation:

how much blood loss?

describe blood-- contents

•  Rising ________ levels in the early follicular phase induce endometrial healing leading to cessation of menstruation

At the end of the luteal phase,

what type of levels do you see of

serum estradiol, progesterone and LH?

What is the criteria for being the dominant follicle used during mensturation?

(3)

Pregnancy

•  Fertilized oocyte becomes a zygote which secretes human chorionic gonadotropin

What can cause a miscarriage during weeks 6 or 7?

how can YOU help?

luteal phase defect

give pt progesterone to help

What areas are influences by hormones?

5

endometrium

       endocervix

       breasts

       vagina

       hypothalamus

•  During menstruation the entire endometrium is expelled and only the basal layer remains

•  During the follicular phase, estrogen stimulates endometrial cell growth

•  Stroma thickens and cells elongate to form proliferative endometrium

•  Endometrium reaches maximal thickness at time of ovulation-why? Ready for implantation

What happens to the endometrium during luteal phase?

what becomes the predominant hormone?

•  Predominant hormone shifts from estrogen to progesterone

•  Endometrial changes occur daily

•  Proliferative endometrium  changes to secretory endometrium

•  Endometrial stroma become loose and edematous, white blood vessels entering the endometrium become thickened and twisted

•  Endometrial glands which were straight and tubular during the proliferative phase become tortuous and contain secretory material within the lumen

If woman doesn’t ovulate, she doesn’t make progesterone- what happens?

What happens to lining of uterus- lining will grow and outgrow support and will have acyclic non-predictable bleeding- could be spotting to hemorrhaging (like an iceberg that grows and loses its support so then sloughs off) what’s tx? Give progesterone

Why is it important for cervix to produce mucous?

What hormone helps with this process?

Cervix: estrogen will make mucous clear, water, very imp! Helps catch sperm; activates sperm, helps with fertilization of egg;

What hormone allows for pubertal breast development?

What hormone is responsible for reproductive changes?

What hormone allows for pubertal breast development?

 estrogen

What hormone is responsible for reproductive changes?

progesterone

What is this called:

increased production of androgens in the adrenals, begins at age 6-8

Adrenarche:

involves production of what?

What are some of the stages that take place in pubertal development?

What is important to remember about this process?

- accelerated growth

   - breast development (thelarche)

   - pubic hair development (pubarche)

   - maximum growth rate

   - menarche

   - ovulation

NEEDS  TO BE IN ORDERLY PREDICTABLE SEQUENCE

Put these in the right order

Thelarch: breast development

Menarche: menstruation

Pubarche: pubic hair

Thelarch: breast development

Pubarche: pubic hair

Menarche: menstruation

If obese: earlier menarche, early development: bc of peripheral conversion of androgen (androdenstione-part of adrenal secretions-converted to estrogen)

Athletic→ slightly delayed menarche bc less body fat

•       Precocious puberty

•       Primary amenorrhea

•       Delayed sexual maturity

•       Incomplete sexual maturation

What is this:

the onset of secondary sexual characteristics prior to age 6 in black girls and age 7 in white girls

What causes precocious puberty?

What do you measure?

•   Precocious puberty is caused either by GnRH-dependent or GnRH independent sex hormone production

•   Measure pituitary FSH and LH to distinguish between a hypothalamic-pituitary from a gonadal etiology

If a test revealed Elevated 17-hydroxyprogesterone

what are you thinking?

pathognomonic of 21-hydroxylase deficiency

Adrenal Causes of Precocious Puberty

Adrenal tumors-rare

Enzyme-secreting defects

•   congenital adrenal hyperplasia (CAH)

•   21-hydroxylase deficiency  is the most common form of CAH

•   presents at birth with ambiguous genitalia

•    adrenal glands unable to produce adequate amount of cortisol because of a partial block in the conversion of 17-hydroxyprogesterone to deoxycortisol

•   results in shunting away from production of cortisol  towards the production of of androgens  (testosterone and estradiol) which results in precocious puberty

•   Snydrome characterized by premature menarche, often the first sign, multiple bone fractures, café-au-lait spots and precocious puberty

Thought to result from a mutation whereby the ovary can produce estrogen without FSH stimulation

•   Puberty is considered delayed when secondary sex characteristics have not appeared by age 13,  there is no evidence of menarche by age 15-16, or when menses have not begun 5 years after thelarche

Hypergonadotropic Hypogonadism (FSH >30mIU/mL)

•       Gonadal dysgenesis (Turners syndrome)

 Hypogonadotropic Hypogonadism      

        (FSH & LH <10mIU/ml)

•        Constitutional (physiologic) delay

•       Kallmann syndrome

•       Anorexia/Extreme exercise

•       Pituitary tumors/ pituitary disorders

•       Drug use

 Anatomic Causes

Mullerian agenesis

Pt presents with amenorrhea, short stature, webbed neck, shield chest with widely spaced nipples, increased carrying angle of the elbows.

What could it be?

•   Estrogen administration should be initiated at the normal time of initiation of puberty

•   Growth hormone should be initiated early and aggressively, often before estrogen therapy to normalize adult height

•   Low-dose estrogen therapy is started to initiate sexual maturation and is increased once breast budding begins

•   If large dosages of estrogen are given initially epiphyseal closure may begin resulting in short stature adults

•   Delay of estrogen therapy may result in teenage osteoporosis

Progesterone should not be added until Tanner stage IV, because premature progesterone administration may prevent complete development of the breast

Most common: physiologic/constitutional delay

Other causes are: Kallmann syndrome, anorexia, exercise, stress, pituitary tumors, pituitary disorders, hyperprolactemia and drug use

•       Arcuate nucleus does not secrete GnRH and the olfactory tracts are hypoplastic

•       Women have little or no sense of smell and lack breast development

Prognosis for treatment and restoration of sexual maturation and reproduction is excellent with the use of exogenous hormones or pulsatile GnRH

•   Weight loss

•   Strenuous exercise (ballet, long-distance running)

•   Anorexia nervosa or bulimia

•   Stress

Craniopharyngioma-most common tumor associated with delayed puberty. Tumor develops in the pituitary stalk.

pt presents with pain in the area of the uterus and bulging, bluish appearing vagina.

What is it?

Primary Amenorrhea: Imperforate Hymen

•   Simplest genital tract anomaly to treat

•   Lower vagina and mid-portion of the vagina form from canalization of the genital plate

•   Imperforate hymen results from incomplete canalization and hymen is closed

Mullerian ducts develop and fuse in the female fetus to form the upper reproductive tract (fallopian tubes, uterus, and upper vagina-NOT VAGINA)

Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser syndrome is the most common cause of primary amenorrhea in women with normal breast development

Syndrome associated with congenital absence of the vagina, and often the uterus and fallopian tubes

Ovarian function is normal so all secondary sexual characteristics of puberty occur at appropriate time

Renal anomalies occur in 40%-50% of patients

What does this describe?

Phenotypically- develop beautifully like women

Genetically they are XY: males