Female reproductive system II Enas Omar Notes are in green · H-P-O axis 1.Positive feedback Sex...

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Female reproductive system II Enas Omar Notes are in green

Transcript of Female reproductive system II Enas Omar Notes are in green · H-P-O axis 1.Positive feedback Sex...

Page 1: Female reproductive system II Enas Omar Notes are in green · H-P-O axis 1.Positive feedback Sex hormones (E)↑ → GnRH or LH/FSH↑ E peak (≥200pg/ml) → LH/FSH peak → During

Female reproductive system II Enas Omar Notes are in green

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Copyright © 2011 by Saunders, an imprint of Elsevier I

C.Luteal phase

nc.

a. Interval between ovulation and menstrual flow (15th - 28th day.(

b. Duration is κ: 14±2 d (t½ = corpus luteum.(

c. Day of ovulation = Length of the menstrual cycle - 14d

d. Predominant Hormone: Progesterone

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Corpus luteum

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• Provides necessary hormones for implantation of blastocyst and maintenance of zygote until placenta can take over

Corpus luteum is composed mainly of

granulosa cells

80 % granulosa cells, 20% thecal cells

If not fertilization, will regress in about 14 d

Avascular scar = corpus albicans

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.

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4 14 28

ovulation

Endometrial 1

Cycle: menstrual proliferative

phase (11 d)

secretory phase (12d)

Ovarian

Cycle: follicular phase luteal phase

(FORMAT FOR NEXT

FEW SLIDES)

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ovulation LH

surge

Ovarian

Cycle:follicular phase FSH and LH in the

Follicular phase

LH surge lasts 48 h

secretory phase (12d) 28 proliferative phase

(11 d)

FSH

LH

1 4 14

Endometrial

Cycle: menstrual

Inc

GnRH

bursts

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1 4 14

ovulation

LH

surge

Proliferative

phase Endometrial

Cycle:

estradiol

feedback--G

nRH

Secretory phase (12d) 28

neg

Ovarian

Cycle: follicular phase

Increase in estradiol to stimulate

LH surge. Then estradiol has

negative feedback on GnRH to

reduce LH, FSH.

FSH

LLHH

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1 4 14

ovulation

Proliferative phase Endometrial

Cycle: menstrual

Ovarian

Cycle: follicular phase

activin

inhibin

Secretor

y phase

(12d)28

_

FSH

Granulosa cells

Activin inhibin

+

Changes in activin and inhibin in

follicular phase.

FSH

activin

inhibin

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Inhibin : a hormone secreted by sertoli cells in the male & the granulosa cells in the female . It inhibits the production of FSH by the ant pituitary . Activin :if there is no formation of ovum .. It’s secreted to enhance FSH secretion.

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4 14

ovulation

Proliferative phase

(11 d(

1

Endometrial

Cycle:menstrual

Ovarian

Cycle: follicular phase

progesterone

activin

inhibin

28

Changes in progesterone

in follicular phase.

progesterone

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The uterine cycle and normal menstruation:

Because of the monthly cyclic production of estrogens and progesterone, the endometrial lining of the uterus passes into three phases. They are; Proliferative phase, Secretory (or luteal phase), and menstrual phase . These changes are mainly to prepare the uterus for implantation

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At the beginning of each monthly cycle most of the endometrium has been desquamated by menstruation , after that only a thin layer of stroma remains & proliferate under the influence of estrogen . Then endometrial changes occur to produce a highly secretory endometrium to provide appropriate conditions for implantation of a fertilized ovum

You can see that the thickness in the beginning is completely different from that of the end

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1-Proliferative phase

• It is about 9-11 days in duration. • Estrogen secreted in increasing quantities by the

developing follicle causes proliferation of the epithelial cells left after endometrial desquamation.

• Endothelial re-epithelialization occurs within 4-7 days after the beginning of menstruation (when bleeding ceases.)

• The next 7-10 days the endometrial thickness increases greatly to about 3-5 mm (formation of new endometrial glands and blood vessels.)

• The mucus strings secreted by the endometrial glands (especially these of the cervix), align in the cervical canal, forming channels that guide sperm in the proper direction from vagina into the uterus.

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• The length of this phase is remarkably constant at about 14 days.

• Occurs after ovulation (the second half of the cycle.) • Estrogens cause slight additional cellular proliferation, whereas

progesterone causes marked swelling and secretory development with further increase in blood supply to the endometrium. Both blood vessels and glands become highly tortuous.

• Lipid and glycogen deposit greatly in the stromal cells. • The peak of the secretory phase is about 1 week after ovulation.

At this time, the endometrial thickness reaches to 5-6 mm. • During the secretory phase, the endometrium provides appropriate conditions for implantation of a fertilized ovum.

• The fertilized ovum needs 3-4 days to enter the uterine cavity from fallopian tube and another 4-5 days for implantation. During this intervals uterine secretions (uterine milk) provide nutrition for the early dividing ovum.

• Once the ovum implants, trophoblastic cells of the blastocyst begin to digest the endometrium.

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Phase 1 : estrogen Phase 2 : progesterone

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3. Normal menstruation

• Occurs when fertilization fails to occur during the secretory phase (involution of corpus luteum.)

• The usual duration of the menstrual flow is 3-5 days (1-8 days range). Blood loss reaches up to 80 ml (average 30-40 ml). Bleeding can increase because of medications and diseases that affect the clotting mechanism. Formation of a clot indicates abnormality

• 24 hours before menstruation blood vessels leading to the mucosal layers become vasospastic, presumably because of vasoconstrictor types of prostaglandins.

• The vasospasm + ↓ nutrients + ↓ hormonal stimulation

endometrial necrosis Hemorrhage + Sloughing of outer layers of the

endometrium

• Prostaglandins and desquamated tissues initiate uterine contractions that expel the uterine contents.( necrotic substances ) • The menstrual fluid is normally non-clotting because of released fibrinolysin.

Clots presence may indicate uterine pathology. • Menstrual flow is rich in leukocytes. This outflow of leukocytes may explain

the resistance of uterus to infection during menstruation despite the denuded endothelial surface.( a protective mechanism)

• Two imp things to remember : 1-manstrual fluid has no clots 2- it is rich in leukocytes.

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Normal menstruation

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The standard classification

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for patterns of abnormal bleeding

(1)Menorrhagia (hypermenorrhea) is heavy or prolonged menstrual flow during regular period. The presence of clots may not be abnormal but may signify excessive bleeding.

(2)Hypomenorrhea (cryptomenorrhea) is unusually light menstrual flow, sometimes only spotting, during regular period. An obstruction such as hymenal or cervical stenosis may be the cause.

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(3) Metrorrhagia

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(intermenstrual bleeding) is bleeding that occurs

at any time between Not prolonged period but frequent

menstrual periods.

(4) Polymenorrhea describes periods that occur too frequently, usually associated with anovulation and rarely with a

phase in the menstrual Is associated with a disease

shortened luteal cycle. Mostly bleeding

(5)Oligomenorrhea describes menstrual periods that occur more than 35 days apart. Bleeding usually is decreased in amount and associated with anovulation, either from endocrine causes (eg, pregnancy, pituitary-hypothalamic causes, menopause) or systemic causes (eg, excessive weight loss.)

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Cyclic changes in Cervix, vagina & breasts:

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1- Cervix 2- Vagina 3- Breasts

Estrogen:make mucus

Thinner,more alkaline If spread on slide dries in fern like manner

Progesterone:make mucus thick,tenaciuous,more cellular,If spread on slide

doesn’t fern

Estrogen:cornification of vaginal epithelium

Progesterone:thick mucus secretion,proliferation of vaginal epithelium and leucocytes infiltration

Estrogen:Proliferation of breasts ducts

Progesterone:growth of breast lobules & alveoli

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Copyright ©

2011 by Saunders, an imprint of Elsevier Inc.

This diagram shows the relationship b/w hypothalamus , ant pituitary & the ovary Gnrh secreted by the hypothalamus will stimulate the ant pituitary to release LH & FSH and these hormones will stimulate the ovaries to secrete progesterone & estrogen. Estrogens and progestin exert both positive & negative feedback effects on ant pituitary & hypothalamus depending on the stage of the ovarian cycle . Inhibin which is secreted by granulosa cells has a negative feedback effect on the ant pituitary

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H-P-O axis

1.Positive feedback

Sex hormones (E)↑ → GnRH or LH/FSH↑ E peak (≥200pg/ml) → LH/FSH

peak →

During ovulation only.

2.Negative feedback

Sex hormones (E)↑ → GnRH or LH/FSH↓ Follicular phase: E↑ → FSH↓

Luteal phase: E↑P↑ → LH/FSH↓(formation)

E↓P↓ → LH/FSH↑(regres Co

spyrig

iht

o© 201

n1 by Sa

)unders, an

Page 21: Female reproductive system II Enas Omar Notes are in green · H-P-O axis 1.Positive feedback Sex hormones (E)↑ → GnRH or LH/FSH↑ E peak (≥200pg/ml) → LH/FSH peak → During

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28

FSH

ovulation

4 14

Proliferative phase

(11 d(

1

Endometrial

Cycle: menstrual

Secretory phase (12d)

Ovarian

Cycle:

inhibin

activin

_

FSH

Granulosa cells a

Activin inhibin

+

+

Corpus albicans

Luteal phase

The cells that surround the ovum

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1 4 14 28

FSH

ovulation

proliferative phase Endometrial

Cycle:

secretory phase

Ovarian

Cycle:

inhibin

_

FSH +

Luteal phase +

Granulosa cells

Activin inhibin

estradiol

Levels of estradiol in luteal phase

Corpus albicans

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14 28

proliferative phase Endometrial

Cycle:

secretory phase

Ovarian

Cycle: follicular phase

progesterone

Corpus luteum ovulation

Corpus albicans

+

+

_

estradiol

1 4 mens

Produces inhib

GnRH _

Luteal phase

Changes in estradiol

And progesterone

in luteal phase.

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Functions of estradiol

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Fat deposition: more subcutaneous fat in women than men

Estrogens: hips and thighs fat deposition

(prior to menopause) then more abdominal

(Men: androgens: abdominal fat deposition (

Skin: increase vascularization of skin, smooth and soft.

Bones: estrogen inhibits osteoclastic activity, so height

increases after puberty,but epiphyses and shafts of

bones unite early and growth stops

So the more the testosterone & estrogen , the less the tall

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Functions of estradiol

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External female sex organs: at puberty, increase in size of fallopian

tubes, uterus and vagina, external genitalia deposition of fat in mons

pubis , labia majora & labia minora

change vaginal epithelia from cuboidal to stratified type endometrium:

proliferation of cells and endometrial glands

(important in nutrition of fertilized ovum(

Breasts: fat deposition, development of stromal cells, ducts

(progesterone, prolactin important in milk production(

Estrogen affect the size of the breast ,deposition of fat , development

of the stromal tissue &growth of the ductile system .

Progesterone & prolactin complete the job in converting the breasts

into milk-producing organs.

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This diagram shows the relationship b/w Estrogen secretion & the age: From birth till puberty very little amount of estrogen is secreted . Then levels of estrogen secretion increase at puberty. You can notice cyclical variation during the monthly sexual cycle . During the first few years of reproductive life , further increase in estrogen secretion is shown . Then a progressive decrease in estrogen secretion toward the end of reproductive life & finally almost no estrogen secretion beyond menopause.

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When estrogen production fall below critical value , the estrogen the estrogen can no longer inhibit the production of gonadotropins FSH & LH instead they are produced in large & continuous quantities.

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Functions of estrogen and Progesterone:

Estrogen Progesterone

1- Facilitate growth of follicles 1- Causes secretory phase of menstrual cycle

2- growth of ovaries, fallopian tubes, uterus, vagina and female external genitalia,breasts duct system and deposit of fat in the breast.

2- Stimulate developmentof breast lobules & alveoli

3- Produce female 2ry sex characters,body configuration,fat distribution & increase libido

3- Essentia for maitenance of pregnancy and increase secretion of fallopian tubes essential for nutient of fertilized ovum.

4- Produce proliferative phase of

Menstrual cycle,++uterine blood flow,musculature and make it more sensitive to oxytocin

4- Decrease sensitivity of uterus to oxytocin

5- produce cyclic changes in cervix & vagina 5- Produce cyclic changes in cervix & vagina

6- Control FSH&LH secretion & causes the LH surge at midcycle

6- Inhibit LH secretion during pregnancy (producing amenorrhea)

7- Has metabolic anabolic effects, cause epiphyseal closure of bones(also ++bone density),decrease serum cholesterol level,++angiotensinogen secretion from liver,increase HDL,--LDL(Cardioprotective)

Produce salt & water retention. Increase metabolism and fat deposition , slight increase protein deposition.

7- Thermogenic effect(++body temperature by 0.5 C at ovulation)

++respiratory rate ---alveolar CO2

Produce natriuresis

No anabolic functions

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Female sexual act

1-Stimulation of female sexual act : Thinking

lead to sexual desire and this desire change

during the cycle reaching the peak near

ovulation because of high estrogen. Physical

stimulation as in male ( perineal region). Same

nerve signals.

2-Female erection and lubrication (clitoris): as

the penis control by parasympathetic nerves,

same mechanism as in male

3-Female orgasm (female climax):Analog to

emission and ejaculation in male . There is no

ejaculation in females

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Female sexual response

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-- process is similar in males and females:

1)Excitement phase:caused by psychological or physical

stimulation; engorgement and erection of clitoris, vaginal

congestion -- due to NO, secreted by parasympathetic nerves

2)Plateau phase:intensification of these responses, increased

HR, BP, respiratory rate, muscle tension

3)Orgasmic phase:culmination of sexual excitement, intense

physical pleasure

4)Resolution phase:returns genitalia and body systems to

pre-arousal state

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Male and female sexual response

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Differences:

Women don’t require refractory time before beginning

excitation again

No ejaculation in the female

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Female sexual dysfunction

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may be as high as 45% in women aged 16-50 yrs

mechanisms:

psychological illness unknown

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Menopause

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Defn:obsolescence of ovaries, no estradiol production, ova

only occasional secondary follicle, few primary follicles

Occurs at 51.4 yr of age (average(

Due to reduction in estrogen, low levels of inhibin,

no negative feedback of LH and FSH; therefore, high levels

LH and FSH because there is no estrogen &

progesterone

Can occur naturally, due to surgery or as a result of

chemotherapy

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Women’s Health Initiative

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• Increased risk of CHD, stroke, pulm embolis (3x (,

breast cancer

• “HRT regimen should not be initiated or continued for primary prevention of CHD”

• الدكتور علق عالنقطة الثانية بس ما سمعت منيح اللي عنده فكرة عن pinned postالموضوع يحطها بال

JAMA 2002

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ppPP

Physiological changes in the body during menopause 1-Hot flushes 2-Irritability 3-Anxiety 4- Fatigue 5- Psychic dyspnea 6-Decrease strength of the bones 7-Vaginal dryness 8-Gradual atrophy of genital organs Small dose of estrogen reverse these symptoms Some of these symptoms can develop in men when they reach the age of reduced sexual activity

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Polycystic ovary syndrome

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Affects 10% of reproductive age women

Characteristics: hyperandrogenemia

oligomenorrhea obesity

hirsutism

Infertility this is the main problem

enlarged cystic ovaries

Rx: metformin, anti-androgens?

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Abnormal secretion of the ovaries:

1-Hypogonadism reduce secretion

A- Before puberty cause infantile sexual

organs, no secondary sexual character and

tall female

B- After puberty cause infantile sexual organs

include the uterus, small vagina, breast

atrophy

C-Irregularity of menses and amenorrhea.

2-hypersecretion rare (granulosa cell tumor)

and mainly cause irregular bleeding.

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Female fertility: 1-Fertile period of each cycle (4-5 days), before

ovulation

2-Rhythm method for contraceptive (the successful rate75%).one of the commonly

practiced methods of contraceptive is to avoid intercourse near the time of ovulation at least

2 days before & 2 days after the ovulation . This is a physiological contraceptive .

3- Hormonal suppression of fertility (the pills) : use

of estrogen or progesterone in the first half of the

cycle prevent ovulation by prevent preovulatory

surge of LH secretion by pituitary gland (successful rate90%).

4- Female sterility :

A-Failure of ovulation mainly reduce gonadotropin

hormone mainly

B-Endometriosis , salpingitis( inflammation of fallopian tube , this cause fibrosis

,thereby occluding the tubes & preventing sperms from reaching the ovum .)

A student asked : what is the cause of ovulation failure ?

Answer : ovulation is gonadotropin dependent so any thing that affect the availability of

gonadotropins during ovulation period can affect this process .