Reprod Syst Female & Menopause 2006, Concise

8/10/2019 Reprod Syst Female & Menopause 2006, Concise

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ENDOCRINOLOGY OFENDOCRINOLOGY OF

THE REPRODUCTIVE SYSTEMTHE REPRODUCTIVE SYSTEM

M. Djauhari WidjajakusumahM. Djauhari Widjajakusumah


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THE FEMLETHE FEMLE

REPRODUCTIVE SYSTEMREPRODUCTIVE SYSTEM


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Ovarian CycleOvarian Cycle

Follicle Development - Follicular PhaseFollicle Development - Follicular Phase



Primordial folliclePrimordial follicle

formed during fetal life (3rd - 7th month)formed during fetal life (3rd - 7th month)

contains a primary oocyte surrounded by a single layer of granulosacontains a primary oocyte surrounded by a single layer of granulosa

cellscells

more than 2000.000 in each ovary at birthmore than 2000.000 in each ovary at birth

Primary folliclePrimary follicle

consists of a primary oocyte surounded by multiple layers of granulosaconsists of a primary oocyte surounded by multiple layers of granulosa

cells and a layer of theca cellscells and a layer of theca cells

developed from several primordial follicles each month starting atdeveloped from several primordial follicles each month starting at

puberty (10-1 yrs)puberty (10-1 yrs)


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!econdary follicle!econdary follicle

developed from primary follicles at the beginning of eachdeveloped from primary follicles at the beginning of each

cyclecycle

in response to the rising levels of "!#in response to the rising levels of "!# granulosa cells continue to proliferate$ secrete a fluid$granulosa cells continue to proliferate$ secrete a fluid$

forming a fluid-filled cavity% antrumforming a fluid-filled cavity% antrum


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&esicular ' raafian ' ature follicle&esicular ' raafian ' ature follicle

only one secondary follicle (dominant follicle) completelyonly one secondary follicle (dominant follicle) completely

maturesmatures raafian follicle* other secondary folliclesraafian follicle* other secondary follicles

disintegrate ' atresia (atretic follicles)disintegrate ' atresia (atretic follicles)

raafian follicle rupturesraafian follicle ruptures ovulation (at about the 1thovulation (at about the 1th

day of the cycle)day of the cycle) secondary oocyte e+ected into thesecondary oocyte e+ected into the

open end of "allopian tubeopen end of "allopian tube


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Follicular AtresiaFollicular AtresiaFollicular AtresiaFollicular Atresia

, n mammals$ ./ of all the follicles (oocytes) die by atresia.n mammals$ ./ of all the follicles (oocytes) die by atresia.

nlynly 00 reach ovulatory stage00 reach ovulatory stage

, fundamental property of atresia is the activation of apoptosis fundamental property of atresia is the activation of apoptosisin the oocyte and granulosa cells. poptosis is a complein the oocyte and granulosa cells. poptosis is a comple

process involving ligand signaling path4ays that are coupled toprocess involving ligand signaling path4ays that are coupled tocell death.cell death.

, 5he importance of "!# in preventing apoptosis has led to the5he importance of "!# in preventing apoptosis has led to theconcept that "!# is a follicle survival factorconcept that "!# is a follicle survival factor

, 5he physiological mechanisms governing atresia remain poorly5he physiological mechanisms governing atresia remain poorlyunderstood.understood.


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THE MENSTRUAL CYCLETHE MENSTRUAL CYCLE

6egular cyclic changes of the reproductive system of6egular cyclic changes of the reproductive system of4omen4omen

6egarded as periodic preparation for fertiliation and6egarded as periodic preparation for fertiliation and

pregnancypregnancy

Periodic vaginal bleeding that occurs 4ith the shedding ofPeriodic vaginal bleeding that occurs 4ith the shedding of

the uterine mucosa (menstruation)the uterine mucosa (menstruation)

8ength of the cycle is variable* average figure is 29 days8ength of the cycle is variable* average figure is 29 days

varian cycle and uterine cyclevarian cycle and uterine cycle


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ParturitionParturitionParturitionParturition

, :strogens increase the number of oytocin receptors in:strogens increase the number of oytocin receptors inmyometrium ; 100 during pregnancymyometrium ; 100 during pregnancy

, 6eaches its pea< during early labor6eaches its pea< during early labor

, =terine distention late in pregnancy may also increase the=terine distention late in pregnancy may also increase thenumber of oytocin receptorsnumber of oytocin receptors

, ncreased number of oytocin receptors causes uterus toncreased number of oytocin receptors causes uterus torespond to normal plasma oytocin concentration in therespond to normal plasma oytocin concentration in theearly labor stageearly labor stage


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:strogens:strogens ncreased oytocin receptorsncreased oytocin receptors =terine distention=terine distention

ProstaglandinProstaglandin

=terine contractions=terine contractions

>ilatation of cervi and distention of vagina>ilatation of cervi and distention of vagina

!timuli from cervi and vagina!timuli from cervi and vagina

ncreased secretion of oytocinncreased secretion of oytocin


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ytocin increases unterine contractins in t4o 4ays%ytocin increases unterine contractins in t4o 4ays%

1.1. cts directly on myometrium$ uterine smooth musclescts directly on myometrium$ uterine smooth muscles

contractcontract

2.2. !timulates prostaglandins formation in the decidua.!timulates prostaglandins formation in the decidua.

Prostaglandins enhance the oytocin-induced contractionsProstaglandins enhance the oytocin-induced contractions

!pinal reflees and voluntary contractions of abdominal!pinal reflees and voluntary contractions of abdominal

muscles also aid in deliverymuscles also aid in delivery


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MENOPAUSEMENOPAUSE

enopause is the time in a 4oman?s life 4hen the function of theenopause is the time in a 4oman?s life 4hen the function of the

ovaries ceases.ovaries ceases.

enopause is defined as absence of menstrual periods for 12enopause is defined as absence of menstrual periods for 12

months.months.

5he menopausal transition starts 4ith varying menstrual cycle length5he menopausal transition starts 4ith varying menstrual cycle length

and ends 4ith the final menstrual period.and ends 4ith the final menstrual period.

Perimenopause means @around the time of menopause.APerimenopause means @around the time of menopause.A

Postmenopause is the entire period of time that comes after the lastPostmenopause is the entire period of time that comes after the last

menstrual period.menstrual period.


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MENOPAUSEMENOPAUSE

Bet4een the ages of C - CC yearBet4een the ages of C - CC year

may occur as earlier as the 30s or 0s or may not occur until amay occur as earlier as the 30s or 0s or may not occur until a

4oman reaches her D0s.4oman reaches her D0s.

=nresponsiveness of human ovaries to gonadotropin 4ith advancing=nresponsiveness of human ovaries to gonadotropin 4ith advancing

ageage

>eclining function of the ovaries --; seual cycles disappear>eclining function of the ovaries --; seual cycles disappear

(menopause)(menopause)

>eclining number of primordial follicle>eclining number of primordial follicle

Eo appreciable Fuantities of ovarian progesterone and estradiolEo appreciable Fuantities of ovarian progesterone and estradiol

trophic uterus and vaginatrophic uterus and vagina

ncreased "!# and 8#ncreased "!# and 8#


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THE PERIMENOPAUSAL AND MENSTRUAL CYCLICITYTHE PERIMENOPAUSAL AND MENSTRUAL CYCLICITY

P:6:EP=!:P:6:EP=!:

"ollicle pool"ollicle pool

inhibininhibin "!# "!# cceleration of "ollicularcceleration of "ollicularaturationaturation

!horter Gycle!horter Gycle"ollicle Pool"ollicle Pool

:stradiol >elayed () feedbac< 8onger Gycle:stradiol >elayed () feedbac< 8onger Gycle

:EP=!::EP=!: "ollicle Pool"ollicle Pool

:stradiol:stradiol 8#8# "!# Gycle rrest"!# Gycle rrest


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MENOPAUSEMENOPAUSE

Gommon !ymptomsGommon !ymptoms

#ot flashes ' hot flushes (7C/)% 4armth sensation spreading#ot flashes ' hot flushes (7C/)% 4armth sensation spreadingfrom trun< to facefrom trun< to face

prevented by estrogen treatmentprevented by estrogen treatment

un


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MENOPAUSEMENOPAUSE


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MENOPAUSEMENOPAUSE

Vaginal symptomsVaginal symptoms

I result of the lining tissues of the vagina becoming thinner$ dryer$ result of the lining tissues of the vagina becoming thinner$ dryer$

and less elastic as estrogen levels fall.and less elastic as estrogen levels fall.

I !ymptoms may include vaginal dryness$ itching$ or irritation!ymptoms may include vaginal dryness$ itching$ or irritation

and'or pain 4ith seual intercourse (dyspareunia).and'or pain 4ith seual intercourse (dyspareunia).

I 5he vaginal changes also lead to an increased ris< of vaginal5he vaginal changes also lead to an increased ris< of vaginal

infections.infections.

Vaginal symptomsVaginal symptoms

I result of the lining tissues of the vagina becoming thinner$ dryer$ result of the lining tissues of the vagina becoming thinner$ dryer$

and less elastic as estrogen levels fall.and less elastic as estrogen levels fall.

I !ymptoms may include vaginal dryness$ itching$ or irritation!ymptoms may include vaginal dryness$ itching$ or irritation

and'or pain 4ith seual intercourse (dyspareunia).and'or pain 4ith seual intercourse (dyspareunia).

I 5he vaginal changes also lead to an increased ris< of vaginal5he vaginal changes also lead to an increased ris< of vaginal

infections.infections.


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MENOPAUSEMENOPAUSE

Urinary symptomsUrinary symptoms

I 5he lining of the urethra undergoes changes similar to the tissues5he lining of the urethra undergoes changes similar to the tissues

of the vagina$ becomes dryer$ thinner$ and less elastic 4ithof the vagina$ becomes dryer$ thinner$ and less elastic 4ith

declining estrogen levels.declining estrogen levels.

I Gan lead to an increased ris< of urinary tract infection$ feeling theGan lead to an increased ris< of urinary tract infection$ feeling the

need to urinate more freFuently$ or lea


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MENOPAUSEMENOPAUSE

Emotional and cognitive symptomsEmotional and cognitive symptoms

I Jomen in perimenopause often report a variety of cognitiveJomen in perimenopause often report a variety of cognitive

(thinifficult to determine 4hich behavioral symptoms are due directly>ifficult to determine 4hich behavioral symptoms are due directly

to the hormonal changes of menopauseto the hormonal changes of menopause

I Eight s4eats that can also contribute to feelings of tiredness andEight s4eats that can also contribute to feelings of tiredness and

fatigue$ 4hich can have an effect on mood and cognitivefatigue$ 4hich can have an effect on mood and cognitiveperformanceperformance

I any 4omen may be eperiencing other life changes during theany 4omen may be eperiencing other life changes during the

time of perimenopause or after menopause$ such as stressful lifetime of perimenopause or after menopause$ such as stressful life

events$ that may also cause emotional symptoms.events$ that may also cause emotional symptoms.

Emotional and cognitive symptomsEmotional and cognitive symptoms

I Jomen in perimenopause often report a variety of cognitiveJomen in perimenopause often report a variety of cognitive

(thinifficult to determine 4hich behavioral symptoms are due directly>ifficult to determine 4hich behavioral symptoms are due directly

to the hormonal changes of menopauseto the hormonal changes of menopause

I Eight s4eats that can also contribute to feelings of tiredness andEight s4eats that can also contribute to feelings of tiredness and

fatigue$ 4hich can have an effect on mood and cognitivefatigue$ 4hich can have an effect on mood and cognitiveperformanceperformance

I any 4omen may be eperiencing other life changes during theany 4omen may be eperiencing other life changes during the

time of perimenopause or after menopause$ such as stressful lifetime of perimenopause or after menopause$ such as stressful life

events$ that may also cause emotional symptoms.events$ that may also cause emotional symptoms.


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MENOPAUSEMENOPAUSE

OsteoporosisOsteoporosisI steoporosis is the deterioration of the Fuantity and Fuality ofsteoporosis is the deterioration of the Fuantity and Fuality of

bone that causes an increased ris< of fracture.bone that causes an increased ris< of fracture.

I 5he density of the bone (bone mineral density) normally begins to5he density of the bone (bone mineral density) normally begins to

decrease in 4omen during the fourth decade of life.decrease in 4omen during the fourth decade of life.I Eormal decline in bone density is accelerated during theEormal decline in bone density is accelerated during the

menopausal transition.menopausal transition.

I ge and the hormonal changes due to the menopause transitionge and the hormonal changes due to the menopause transition

act together to cause osteoporosis.act together to cause osteoporosis.

I 5he process leading to osteoporosis can operate silently for5he process leading to osteoporosis can operate silently fordecades. Jomen may not be a4are of their osteoporosis untildecades. Jomen may not be a4are of their osteoporosis untilsuffering a painful fracture.suffering a painful fracture.

OsteoporosisOsteoporosisI steoporosis is the deterioration of the Fuantity and Fuality ofsteoporosis is the deterioration of the Fuantity and Fuality of

bone that causes an increased ris< of fracture.bone that causes an increased ris< of fracture.

I 5he density of the bone (bone mineral density) normally begins to5he density of the bone (bone mineral density) normally begins to

decrease in 4omen during the fourth decade of life.decrease in 4omen during the fourth decade of life.I Eormal decline in bone density is accelerated during theEormal decline in bone density is accelerated during the

menopausal transition.menopausal transition.

I ge and the hormonal changes due to the menopause transitionge and the hormonal changes due to the menopause transition

act together to cause osteoporosis.act together to cause osteoporosis.I 5he process leading to osteoporosis can operate silently for5he process leading to osteoporosis can operate silently for

decades. Jomen may not be a4are of their osteoporosis untildecades. Jomen may not be a4are of their osteoporosis untilsuffering a painful fracture.suffering a painful fracture.

OSTEOBLASTOGENESS OSTEOCLASTOGENESSOSTEOBLASTOGENESS OSTEOCLASTOGENESS


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OSTEOBLASTOGENESS - OSTEOCLASTOGENESSOSTEOBLASTOGENESS - OSTEOCLASTOGENESS

Bone arro4 GultureBone arro4 Gulture

"ibroblast Golony- ranulocyte-acrophag"ibroblast Golony- ranulocyte-acrophag"orming =nit Golony "orming =nit"orming =nit Golony "orming =nit

(steoprogenitor cells) (#ematopoetic cells)(steoprogenitor cells) (#ematopoetic cells)steoblast$ "ibroblast steoclast$ onocytessteoblast$ "ibroblast steoclast$ onocytesGhondrocytes$ dipocytes acrophage ProgenitorsGhondrocytes$ dipocytes acrophage Progenitors ProgenitorsProgenitors

PT!PT!

CalcitriolCalcitriol 6EK-86EK-8"-# "-#steoblastic :arly pre-osteoclaststeoblastic :arly pre-osteoclast

precursor cellsprecursor cells ()()

8ate pre-osteoclast8ate pre-osteoclast Estro$enEstro$en

()() ()() An%ro$enAn%ro$en ()() steoblaststeoblast steoclaststeoclast

"-1"-1 Bone 6esorptionBone 6esorption

Bone "ormingBone "orming (RANK: receptor activator of nc!ear factor "appa #$ %(RANK: receptor activator of nc!ear factor "appa #$ %(OD&: o'teoc!a't ifferentiation factor$(OD&: o'teoc!a't ifferentiation factor$


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Osteo&last ' Osteoclast CommunicationOsteo&last ' Osteoclast CommunicationOsteo&last ' Osteoclast CommunicationOsteo&last ' Osteoclast Communication

osteoblast (L osteoblast precursors)osteoblast (L osteoblast precursors)

estrogensestrogens -- glucocorticoidsglucocorticoids -- estrogensestrogens

P5#P5#

osteoprotegerin (P) P-ligandosteoprotegerin (P) P-ligand

free-floating decoy receptorfree-floating decoy receptor (6EK ligand) (6EK ligand)

osteoclast precursors osteoclastosteoclast precursors osteoclast

6EK receptor6EK receptor 6EK receptor6EK receptor

osteoclast activityosteoclast activity

6EK ligand6EK ligand bone resorptionbone resorption

(osteoblast)(osteoblast)

P5#$ >#G (vit >P5#$ >#G (vit >33)$ 8 1- - D-11-17$ 5E"-alfa)$ 8 1- - D-11-17$ 5E"-alfa

osteoblast (L osteoblast precursors)osteoblast (L osteoblast precursors)

estrogensestrogens -- glucocorticoidsglucocorticoids -- estrogensestrogens

P5#P5#

osteoprotegerin (P) P-ligandosteoprotegerin (P) P-ligand

free-floating decoy receptorfree-floating decoy receptor (6EK ligand) (6EK ligand)

osteoclast precursors osteoclastosteoclast precursors osteoclast

6EK receptor6EK receptor 6EK receptor6EK receptor

osteoclast activityosteoclast activity

6EK ligand6EK ligand bone resorptionbone resorption

(osteoblast)(osteoblast)

P5#$ >#G (vit >P5#$ >#G (vit >33)$ 8 1- - D-11-17$ 5E"-alfa)$ 8 1- - D-11-17$ 5E"-alfa


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MENOPAUSEMENOPAUSE

Cardiovascular diseaseCardiovascular diseaseI Prior to menopause$ 4omen have a decreased ris< of heartPrior to menopause$ 4omen have a decreased ris< of heart

disease and stro


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MENOPAUSEMENOPAUSE

Hormone therapyHormone therapyI :strogen and progesterone therapy:strogen and progesterone therapy

I ral contraceptive pillsral contraceptive pills

I Plant estrogens (phytoestrogens$ isoflavones)Plant estrogens (phytoestrogens$ isoflavones)I 8ocal (vaginal) hormone treatments8ocal (vaginal) hormone treatments

Antidepressant medicationsAntidepressant medications

Lifestyle factors in controlling the symptoms andLifestyle factors in controlling the symptoms andcomplications of menopausecomplications of menopause

Hormone therapyHormone therapyI :strogen and progesterone therapy:strogen and progesterone therapy

I ral contraceptive pillsral contraceptive pills

IPlant estrogens (phytoestrogens$ isoflavones)Plant estrogens (phytoestrogens$ isoflavones)

I 8ocal (vaginal) hormone treatments8ocal (vaginal) hormone treatments




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MENOPAUSEMENOPAUSE


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MENOPAUSEMENOPAUSE

Hormone therapyHormone therapy8ocal (vaginal) hormone treatments8ocal (vaginal) hormone treatments

, &aginal hormonal treatments for the symptoms of vaginal&aginal hormonal treatments for the symptoms of vaginalestrogen deficiency.estrogen deficiency.

, nclude the vaginal estrogen ring$ vaginal estrogen cream$ ornclude the vaginal estrogen ring$ vaginal estrogen cream$ orvaginal estrogen tablets.vaginal estrogen tablets.

, 8ocal and oral estrogen treatments are sometimes combined.8ocal and oral estrogen treatments are sometimes combined.

Hormone therapyHormone therapy8ocal (vaginal) hormone treatments8ocal (vaginal) hormone treatments

, &aginal hormonal treatments for the symptoms of vaginal&aginal hormonal treatments for the symptoms of vaginalestrogen deficiency.estrogen deficiency.

, nclude the vaginal estrogen ring$ vaginal estrogen cream$ ornclude the vaginal estrogen ring$ vaginal estrogen cream$ orvaginal estrogen tablets.vaginal estrogen tablets.

, 8ocal and oral estrogen treatments are sometimes combined.8ocal and oral estrogen treatments are sometimes combined.

MENOPAUSEMENOPAUSE


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MENOPAUSEMENOPAUSE


I :ffective in controlling the symptoms of hot flashes in up to D0/ of:ffective in controlling the symptoms of hot flashes in up to D0/ of4omen.4omen.

I ay be associated 4ith side effects$ including decreased libido oray be associated 4ith side effects$ including decreased libido orseual dysfunction.seual dysfunction.


I :ffective in controlling the symptoms of hot flashes in up to D0/ of:ffective in controlling the symptoms of hot flashes in up to D0/ of4omen.4omen.

I ay be associated 4ith side effects$ including decreased libido oray be associated 4ith side effects$ including decreased libido or

seual dysfunction.seual dysfunction.

MENOPAUSEMENOPAUSE


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MENOPAUSEMENOPAUSE


I any of the symptoms of menopause and the medicalany of the symptoms of menopause and the medicalcomplications that may develop in postmenopausal 4omen cancomplications that may develop in postmenopausal 4omen can

be lessened or even avoided by ta


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Mammary Gland andMammary Gland andLactationLactation

>evelopment of 5he Breasts>evelopment of 5he Breasts

>evelopment of 5he Breasts>evelopment of 5he Breasts


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>evelopment of 5he Breasts>evelopment of 5he Breasts>evelopment of 5he Breasts>evelopment of 5he Breasts

, :strogens are primarily responsible for proliferation of mammary ducts:strogens are primarily responsible for proliferation of mammary ducts

, Progesterone are primarily responsible for the development of theProgesterone are primarily responsible for the development of thelobuleslobules

,Prolactin in humans may also be needed for mammary glandsProlactin in humans may also be needed for mammary glands

development at pubertydevelopment at puberty

, ncreased prolactin levels$ and high levels of estrogens andncreased prolactin levels$ and high levels of estrogens andprogesterone (and possibly hG) cause full breast lobulo-alveolarprogesterone (and possibly hG) cause full breast lobulo-alveolar

development during pregnancydevelopment during pregnancy

, Gortisol$ insulin$ and gro4th hormone are necessary for mammaryGortisol$ insulin$ and gro4th hormone are necessary for mammarydevelopmentdevelopment


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8actation !ecretion and :+ection of il


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8actation I !ecretion and :+ection of il


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y

, Produced by the lactotrophs cells of the anterior pituitary glandProduced by the lactotrophs cells of the anterior pituitary gland

, =nder stimulatory control of thyroid releasing hormone (56#)=nder stimulatory control of thyroid releasing hormone (56#)

, ncreased release at nightncreased release at night

, n females - increased release during pubertyn females - increased release during puberty

, Prolactin levels are high during pregnancy - oestrogen causes anProlactin levels are high during pregnancy - oestrogen causes anincrease in numbers of lactotrophsincrease in numbers of lactotrophs

, >uring lactation$ sucuring lactation$ suc


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P l ti 8 lP l ti 8 l


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Prolactin 8evelsProlactin 8evels

, #igh during pregnancy$ drifts do4n to its normal level after the baby is#igh during pregnancy$ drifts do4n to its normal level after the baby isbornborn

, By the end of the first 4ee< after birth$ prolactin is do4n to C0 percent ofBy the end of the first 4ee< after birth$ prolactin is do4n to C0 percent ofits normal level$ after three or four months$ it is the same as it 4as beforeits normal level$ after three or four months$ it is the same as it 4as beforepregnancypregnancy

, :very time the baby suc


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Gontraceptive effect ofGontraceptive effect of high levels ofhigh levels ofprolactinprolactin


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, n non breast-feeding 4omenn non breast-feeding 4omen

"!# levels Fuicuring lactational amenorrhoea (2C-30 4ee


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, Ee4borns are nourished from their mother?s mil< or from aEe4borns are nourished from their mother?s mil< or from abottle because they can only s4allo4 liFuids.bottle because they can only s4allo4 liFuids.

, !ince ne4borns can only digest about 30 milliliters of mother?s!ince ne4borns can only digest about 30 milliliters of mother?smil< or formula at a time$ they must be fed often$ usually aboutmil< or formula at a time$ they must be fed often$ usually about

every hours.every hours.

, 5hey can lose as much as 10/ of their body 4eights in the first5hey can lose as much as 10/ of their body 4eights in the firstfe4 days after birth because they need more food than they canfe4 days after birth because they need more food than they can

consume. t about the tenth day of life$ the ne4born regainsconsume. t about the tenth day of life$ the ne4born regains

the lost 4eight and starts to gain about 29 grams per day.the lost 4eight and starts to gain about 29 grams per day.


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Tha!k

"#u

Reprod Syst Female & Menopause 2006, Concise

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