PREGNANCY AND MENOPAUSE

2. Explain how and when ovulation occurs

 in normal 28 day cycle in female, ovulation occurs 14 days after onset of menstruation
 follicle swells rapidly -> stigma protrudes like nipple -> viscous fluid evaginate out (carries the ovum
surrounded w/ corona radiata)
 surge of LH is necessary for ovulation
o 2 days before ovulation
 rate of LH secretion (by AP gland) increases markedly
 FSH also increases
o last few days before ovulation
 FSH and LH act synergistically to cause rapid swelling of the follicle
 LH convert granulosa and theca cells into progesterone secreting cells
o 1 day before ovulation
 ↓ estrogen secretion
 Ovulation occurs in an environment of:
o rapid growth of the follicle
o ↓ estrogen secretion (after prolonged phase of excessive estrogen secretion)
o initiation of secretion of progesterone
 INITIATION OF OVULATION:
o LH causes rapid secretion of follicular steroid hormones that contain progesterone
o 2 events needed for ovulation:
 theca externa release proteolytic enzymes from lysosomes -> dissolution of follicular
capsular wall -> weakened wall -> further swelling of entire follicle and degeneration of
the stigma
 rapid growth of new blood vessels into follicle wall and; prostaglandins are secreted into follicular tissues
o the 2 events cause plasma transudation into follicle ->follicle swelling and degeneration of stigma -> follicle rupture -> discharge of ovum
 CORPUS LUTEUM
o After ovulation, secretory cells of the ovulating follicle develop into a corpus luteum
o secrete large quantities of progesterone and estrogen
o after 2 weeks, corpus luteum degenerates
 ↓ estrogen and progesterone
 menstruation begins -> new ovarian cycle
3. Outline the major events and hormonal changes of each phase of the uterine cycle and correlate them with events of the ovarian cycle.
 UTERINE CYCLE OVARIAN CYCLE
- menstrual cycle - describes the development and release of oocyte in the ovary and
- growth and differentiation controlled by estrogen and progesterone changes in follicles
- averages 28 days - average of 28 days
- preparation of endometrium for implantation of fertilized and shedding if
implantation has failed
[ 1st ] Proliferative Phase [ 1st ] Follicular Phase
• Aka follicular or estrogenic phase 
  Gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates
• Coincides with rapid growth of small group ovarian follicles 
 the release of FSH and LH 

 Theca interna secretes estrogen 
  Follicle stimulating hormone (FSH) from the pituitary 

• Estrogen - regeneration of functional layer lost during menstruation o Stimulates the process of follicular growth of a small group of
• Cells of the basal ends of glands proliferate, migrate and form 
new epithelial primordial follicles each month
covering 
  Growth of oocyte - FSH
• Spiral arteries lengthen as functional layer is reestablished 
  primary follicle
• Endometrium is 2-3mm at the end of this phase 
  vesicular/antral follicle
• Proliferative phase = 8 to 10 days 
 o contains the secondary oocyte to be ovulated
o cumulus oophorus
o corona radiate
 mature/ Pre- ovulatory/ Graafian follicle
o forms a bulge at ovary surface
 atretic follicles – primary and antral follicles undergo atresia after dominant
follicle is ovulated
[ 2nd ] Secretory Phase
 (Luteal Phase) [2nd] Luteal Phase
 Starts a result of progesterone secreted by corpus luteum 
  Corpus luteum

 Endometrium reaches its maximum thickness (5mm) during this 
phase
 o Formed by collapse and folding of the granulosa and thecal layers of
o Result of the accumulation of secretions and edema in the 
stroma 
 the follicle’s wall

 IF fertilization occurs, embryo attaches to the uterine 
epithelium o Formation under the influence of LH

o Endometrial thickness and secretory activity are optimal for 
embryonic o For extensive production of progesterone in addition to estrogens

implantation and nutrition 
 o Granulosa lutein cells
o Progesterone inhibits strong contractions of the myometrium 
that  Role in aromatase conversion of androstenedione into
might interfere with embryo implantation 
 estradiol
 Secretory phase = 14 days 
 o Theca lutein cells

 Previously theca interna

 LH causes these cells to produce progesterone and
androstenedione
o Ovulatory LH causes corpus luteum to secrete progesterone (10 to 12
 days) and estrogen

 Without further LH stimulation and in the absence of
pregnancy, cells undergo apoptosis and regression of tissue
 Decrease in progesterone levels: causes

menstruation 

 Decrease in estrogen levels: FSH release resumes

 Stimulates another group of follicles to begin
new 
cycle 

 If pregnancy occurs:

o Trophoblast cells of implanted embryo produce human chorionic
gonadotropin
▪ hCG has similar activity to LH (Maintains corpus
luteum -> Maintains progesterone levels -> No menstruation)

[ 3rd ] Menstrual Phase

 Caused by a decline in progesterone and estrogen levels

o Happens when fertilization does not occur and corpus luteum

degenerates 

 Drop in progesterone
o Causes muscle contraction in the spiral arteries = interrupts normal
blood flow 

o Increased synthesis by arterial cells of prostaglandins = vasoconstriction
and local hypoxia 

 Hypoxic injury cause cells to release cytokines

o Increase permeability and immigration of leukocytes 

o Release collagenase and matrix metalloproteinases (MMPs) that
degrade basement membranes and other ECM components 

 Basal layer of the endometrium is not affected

o Does not depend on progesterone-sensitive spiral arteries 

 Menses

o Major portion of the functional layer detach from the 
endometrium
and slough away 

 Endometrium is reduced to a thin layer ready to begin a new 
cycle after this
phase 

 Menstrual period = 3 to 4 days 

4. Maternal physiologic changes and adaptation to pregnancy.
 weight gain - Due to amniotic fluid, placenta and fetal membrane,  Due to the action of progesterone leads to higher tidal
uterus, breasts, blood, fat accumulation volume

 Metabolism o Enlarging uterus results in increased intra-abdominal pressure
o Increased metabolism due to hormonal changes and increased and elevation of diaphragm
muscle activity (because of weight bearing) 
 o Resting ventilation increases by about 48%
o Basal metabolic rate (BMR) rises by the 4th month 
 o More efficient exchange of gases
o The net effect of maternal fuel adaptations is to increase the  Gastrointestinal changes
use of fat as fuel by the mother and conserve the glucose for o Decreased intestinal motility

the fetus 
  action of progesterone

 Cardiovascular changes  Creates tendency to develop gallstones
o Increase in Cardiac Output
 o Constipation

 Due to increase blood volume  Due to compression of rectum
 Also, higher levels of aldosterone and estrogen leads o Gastric reflux and heart burn

to higher fluid retention which causes the increase in  Due to relaxation of Lower Esophageal Sphincter
blood volume (LES)
o Higher heart rate
  Changes in the skin
o Blood pressure lowers o Hyperpigmentation of nipple areolar complex, linea alba
o Higher RBC production (adaptation to hematoctrit)  Due to increased MSH secretion

o Mild hypertrophy of the heart  Facial melasma

o IVC compression (lower blood flow to RA) o Striae Gravidarum (Pregnancy stretch marks)
o Pelvic vein compression (backflow of blood leads to varicose  Due to abdominal wall stretching
 Leads to pruritus
veins and ankle swelling)  Kidney Function
o Heart is displaced and may lead to a larger cardiac shadow o Rate of urine formation is increased

 Respiratory Adaptation  Due to increased fluid intake and increased load of
o Increase in minute ventilation excretory 
products 

o Higher respiratory rate (RR) o Renal tubules’ (re)absorptive capacity for Na, Cl and water is
o Lower arterial CO2
 increased

 Leads to respiratory alkalosis  Due to increased production of salt and water
o Increased upper respiratory vascularization and capillary retaining 
hormones from the placenta and adrenal
engorgement cortex 

o Relaxation of thoracic cage ligaments
 o Renal blood flow and glomerular filtration rate increase
 Due to renal vasodilation and/or as compensation for
increased tubular reabsorption of Na and water 


 PREGNANCY

AMENORRHEA
 For a female who has not undergone fertilization, the following occurs: 

o Corpus luteum involutes

o No estrogen and progesterone that keep the endometrium 
intact

o Shedding of endometrial lining; thus, menstruation occurs 

 For a female who has undergone fertilization, the following occurs: 

o Formation of Zygote


o Implantation into endometrium as blastocyst

o Trophoblast secretes hCG (Mimics action of LH)

o Corpus luteum still secretes Estrogen and Progesterone
o prevents sloughing off of the endometrium

o No menstruation occurs

HORMONAL CHANGES DURING PREGNANCY

 Human Chorionic Gonadotropin (hCG)
o Primary function: Prevents involution of the corpus luteum at 
the end of the monthly
female cycle, causing it to secrete 
larger quantities of its sex hormones 

o hCG increase prevents sloughing off of the endometrium 
(secreted by the placenta and
the syncytial trophoblast cells) 

o Increase is seen 8 to 9 days after ovulation and rises to 
reach a maximum at about 10 to
12 weeks of pregnancy 

o Decreases back to a lower value by 16 to 20 weeks
 Estrogens 

o Secreted by the syncytial trophoblast cells of the placenta 

o Towards the end of pregnancy, quantity increases to about 
30 times the normal level 

o Estrogen produced by placenta differs from that of the 
ovaries:

 Not synthesized de novo
▪ Formed entirely from androgenic steroid compounds


o Causes enlargement of the mother’s uterus, breast ductal structure, and enlargement of the mother’s female external genitalia

 Relaxes the pelvic ligaments for easier passage of the 
fetus
 Progesterone 

o During early pregnancy, secreted in moderate quantities by 
the corpus luteum 

o Secreted in tremendous amounts in late pregnancy by the 
placenta 

o Causes decidual cells to develop in the uterine endometrium 
(for nutrition of embryo) 

o Decreases the contractility of the pregnant uterus (lowers 
risk for abortion) 

o Helps develop the conceptus even before implantation 
occurs via increasing the secretions of the fallopian tubes 
and uterus (for nutrition) 

o Helps estrogen prepare the mother’s breast for lactation 

 Human Chorionic Somatomammotropin

o Secreted by placenta during the 5th week of pregnancy (increases at this point)
o Increases progressively during the remainder of pregnancy 

o Possible effects: breast development, lactation, formation of proteins similar to GH, decreased insulin sensitivity and decreased utilization of
glucose by mother

CHANGES IN REPRODUCTIVE ORGANS

 Endometrium:
o hCG prevents involution of corpus luteum 

o Prevents menstruation → Cause continuous endometrium 
growth and storage of nutrients rather than being shed in the 
menstruum 

o Glands and blood vessels increase in size and number 

o Vascular spaces fuse to become the placenta 

 Uterus

o Enlargement of the Uterus
o Enlargement is caused by:
 Stretching and marked hypertrophy of muscle cells 
(production of new myocytes is limited) 

 Accumulation of fibrous and elastic tissue especially in the 
external muscle layer 

 Vagina
o Enlargement of the female external genitalia 

o Vaginal walls change:
▪ Increase in mucosal thickness ▪ Loosening of connective tissue ▪ Smooth muscle hypertrophy 

o Papillae of the vaginal epithelium undergo hypertrophy → Hobnailed appearance 

o Pregnancy results in increased elastic fiber degradation and an increase in the proteins necessary for new elastic fiber synthesis → Vaginal wall
prolapse 


 Cervix
 o This rearrangement includes the decrease in collagen and proteoglycan concentrations and increase in water content 

o Uterine glands proliferate, doubling in number compared to 
the non-pregnant female 

o Relax the pelvic ligaments of the mother → sacroiliac joints relatively limber + symphysis pubis becomes elastic → allow easier passage of the
fetus through the birth canal

MENOPAUSE
 ↑ FSH - No more negative feedback mechanism from the estrogen → 
no
inhibition of FSH 

 ↓ Estradiol - Follicle is no longer released → ovulation no longer occurs →
corpus luteum will no longer produce estrogen 

 Types of estrogen:
o E1: Estrone – predominant estrogen during menopause
o E2: Estradiol – predominant estrogen during reproductive
o age
o E3: Estriol – predominant estrogen during pregnancy

HORMONAL CHANGES AND EFFECTS ON REPRODUCTIVE ORGANS

 Uterus
o Shrinks (becomes as small as the uterus during puberty due to reduced level of estrogen)
 No longer enlarges in response to sexual stimulation as it 
once did 

 Sexual stimulation is still possible but takes longer – 
feelings of sexual excitation, orgasm, and fulfillment 
remain 

 Endometrium
o less thickening
 Progesterone promotes the secretory changes in the uterine endometrium during the latter half of the monthly sexual cycle

 Reduced production of progesterone (as in menopause) results to less thickening of the endometrium
 Cervix

o Thinning out
 Cervical glands and cells that line the endocervical canal make mucus in response to the female hormones produced during menstrual
cycle 

 Cessation of these hormones leads to less production of mucus by the glands which leads to thinning of the cervix 

 Vagina

o Dryness due to less lubrication from the decreased mucus 
secretion 

o
SIGNS AND SYMPTOMS OF MENOPAUSE
 Hot flushes

o Mechanism is still not understood
o Believed to be due to fluctuation of estrogen and 
progesterone which impacts the functioning of the hypothalamus (responsible for
controlling body temperature, appetite, sex hormones, and sleep) 

o Not a trouble in the Philippines 

 Mood swings & irritability
o Sleep deprivation

o Horm
o onal imbalance

o Social factors (aging, children are away) 

 Vaginal dryness & itching
o Less lubrication leads to atrophy of cells and contributes to 
itching 

o Desquamated cells lead to decreased lactic acid secretion 
producing an alkaline environment and reducing the 
protective moisture in the
vagina 

 Treatment is usually based on symptoms such as: 

o Use of vaginal lubricants and creams
o Cool environment

o Low-dose antidepressants

o Hormonal replacement 

Case: A female patient was diagnosed with PCOS and she was characterized to Describe the histological changes that happen during the proliferative and
have no ovulation and missed menses. There was also existence of secretory phases of the menstrual cycle
endometrial thickening. What is the most probable sex hormone (Estrogen or ANSWER:
• Proliferative
Progesterone) absent from this patient? Begins during the first day of menstruation
 During this phase, the
ANSWER: endometrium is lined with simple
• A person with PCOS has high amounts of androgens Has male columnar cells
 Regeneration of functional layer lost during menstruation
characteristics (facial and body hair)
 Harder to get pregnant 
 is acted upon by estrogen
 Stromal and epithelial cell proliferation
• Presence of aromatase converts androgens to estrogen 
 ▪ Re-epithelialized after 4-7 days
 Endometrium thickens after a week and a
• Increase in estrogen prematurely inhibits anterior pituitary 
no secretion half
of FSH and LH 
 ▪ Due to the increase in number of the stromal cells and the growth of the
• Lack of FSH and LH leads to no maturation of the follicles 
 No ovulation endometrial glands and new blood vessels
occurs 
 ▪ After this phase, the endometrium is 2-3 mm thick
• TH Note: Follicles will still grow and be filled up with fluid but when 
ovulation Spiral arteries lengthen as functional layer is
do not occur, the follicles simply remain as cysts. Multiple small fluid-filled reestablished 

ovarian cysts and excess androgens present PCOS or POLYCYSTIC OVARIAN Endometrial glands secrete stringy mucus which
Syndrome 
 guide the 
sperm towards the uterus 
• Secretory
 Starts when the
• Since no ovulation occurs, no corpus luteum is formed Corpus luteum is corpus luteum secretes progesterone 
estrogen
 Estrogen causes
responsible for the secretion of 
progesterone
 Leads to no progesterone slight additional cellular proliferation in the 
endometrium

formation 
 Progesterone causes marked swelling and secretory 
development
• Endometrial thickening is still present since estrogen is the hormone of the endometrium
 Blood supply to the endometrium further
responsible for cell proliferation in the endometrium 
 increases in 
proportion to the developing secretory activity

• Menstruation requires an increase in progesterone followed by 
its Progesterone stimulates epithelial cells of the uterine glands 
to
decrease
 No progesterone to begin with -> no menstruation 
 secrete and accumulate glycogen 
▪ Causes them to become
coiled
 Endometrium reaches 5 mm in thickness due to 
accumulation
of secretions and edema of the stroma