Female Reproductive Endocrinology IV Flashcards
Exerts a stimulatory effect on the medullary respiratory drive center
-accounts for increased VT during pregnancy
Progesterone
During pregnancy functional residual capacity and expiratory reserve volume decrease approximately
20%
This 20% decrese in FRC and ERV is because of the
Elevated diaphragm and decrease in chest wall compliance seen in pregnancy
Remember from pulmonary function that a PaO2 of 60% represents about
90% Saturation of Hb with O2
Defined as PaO2 less than 60% or Saturation less than 90%
Hypoxemia
Fetal oxygenation will be maintained so long as maternal PaO2 remains
At or above 60%
Realize that the demands of a growing fetus dramatically increase maternal metabolism; this causes an increase in
-Helps drive increased minute ventilation
CO2 production
A couple of things result from the reduced PaCO2. First, lower PaCO2 creates a pressure gradient that is favorable for the offloading of
Fetal CO2
Second, low PaCO2 results in reduced PACO2, allowing for increased
PAO2
Therefore, the alveolar-to-arterial O2 gradient is favorable for the diffusion of O2 from
Alveoli to blood
During the first trimester, this increases PaO2 to as much as
-facilitates maternal to fetal O2 transfer
106-108 mmHg
Recall that reduced PaCO2 due to increased ventilation is defined as respiratory alkalosis. This is compensated by the renal excretion of HCO3-, such that maternal HCO3- is around
18-21 meq/L
So, the maternal acid-base condition is either
- ) Compensated chronic respiratory alkalosis
2. ) Chronic respiratory alkalosis w/ compensatory metabolic acidosis
During pregnancy, O2 carrying capacity is increased due to
Elevated Hb
The fetal Hb-O2 dissociation curve is shifted to the left due to lower levels of
2,3-DPG
Recall that a leftward shift in the curve causes increased affinity of Hb for O2; thus enabling maximal extraction of O2 from
Maternal Blood
Full term birth is considered to be delivery anywhere between
37 and 42 Weeks
Approximately 5-15% of pregnancies result in preterm birth. This accounts for approximately
70& of neonatal mortality
Secreted from the corpus luteum to soften the pelvic ligaments in preparation for parturition
Relaxin
Serum concentrations of relaxin begin to rise during the
Third trimester
Changes in the levels of CHR, progesterone receptor activity, and production of prostaglandins mediate
Initiation of labor
As term nears. an inflammatory process occurs within the fetal membranes. This is known as
Fetal membrane activation
Within the chorion and amnion this process results in the cessation of production of inhibitors of
Prostaglandin production
Prostaglandins are involved in which two hallmark events during the onset of labor?
Cervical ripening (softening) and myometrial contraction
Cervical softening is also promoted by the actions of an inflammatory infiltrate which results in the release of
Matrix metalloproteases
These metalloproteases degrade cervical
Collagen
In order for labor contractions to occur, there must be synergy and permissive actions between estrogens, prostaglandins, and
Oxytocin
Steadily increases and peaks during delivery
CHR
Stimulates cortisol secretion and cortisol induces the production of surfactant
CRH
In addition to its effects on fetal/neonatal pulmonary function, some surfactant is released into the amniotic fluid where it is believed to exert the inflammatory actions within the myometrium and cervix that promote
Labor
A typical myometrial contraction manifests a slow rise and fall of tension over approximately
1 minute duration
Also dependent on the changing role of estrogens during pregnancy
Myometrial activation
Initially induces uterine growth, but this effect terminates toward term
Estrogen
Although the uterus stops growing, the fetus continues a remarkable rate of growth; this results in tension against the uterine wall. Like most other smooth muscle organs, stretch stimulates
Contraction
In women who breastfeed, there is a special neuroendocrine/hormone system activated.This system is mediated by
Prolactin (PRL) and oxytocin
The processes that enable lactation are established during pregnancy when estrogen stimulates the proliferation of
Mammary ductal epithelial cells
At the same time, mammary alveoli growth is stimulated by
Progesterone
Secreted from anterior pituitary lactotrophs and is under control of numerous factors
PRL
Inhibits PRL secretion via activation of D2 receptors
Dopamine
What are three positive regulators of PRL secretion
E2, Oxytocin, and prolactin-releasing peptide
Within the mammary gland, PRL upregulates
Milk production (lactation)
Milk letdown (the secretion of milk) is prevented during pregnancy due to the combined elevation in maternal serum concentrations of
Estrogens and Progesterone
Maternal estrogen and progesterone levels fall following parturition; this frees the suckling induced neuroendocrine mechanisms which cause
Milk let-down
Suckling activated neural tracts which lead to the inhibition of
Dopamine Secretion
Thus suckling prevents dopamine induced
Inhibition of PRL
Suckling also induces the secretion of oxytocin from the
Posterior pituitary
Maintain milk production and induce milk let-down, respectively
PRL and oxytocin
Another component of the suckling reflex blocks activity within the preoptic nucleus. Recall that this is the site for
GnRH production
Therefore, suckling also disrupts the secretion of
FSH and LH (thus disrupting reproductive cycle)
In addition, PRL can directly suppress
Gonadotropin secretion
A pathologic condition most commonly due to a prolactinoma
Hyperprolactinemia
Symptoms of hyperprolactinemia include
Galactorrhea and reproductive dysfunction
In women, this condition can manifest as amenorrhea, oligomenorrhea, menorrhagia, or regular menses with infertility (attributable to a shortened luteal phase)
Hyperprolactinemia
Can result in loss of libido, erectile dysfunction, premature ejaculation, and impaired spermatogenesis
Hyperprolactinemia in men
As described above, the decline in female fertility begins around age 30-35 years due to less
Follicular recruitment
The peri-menopausal transition generally begins in the mid-late 4th decade and lasts for approximately
3-4 Years
During this transition, the menstrual cycle becomes irregular with periods of
Amenorrhea
Characterized by 12 months of amenorrhea
Menopause
Menopause prior to age 40 is abnormal and is classified as
Primary ovarian insufficiency
The onset of ovarian failure occurs in the presence of increased plasma
FSH
The menopausal transition encompasses approximately 4 years in most women, and during this time frame, we see the greatest rate of change in the pattern of plasma
FSH and E2 levels
Beginning around 2 years preceding the last menstrual period (LMP), FSH begins to rise, and plasma FSH increases steadily until about
2 years after LMP
These changes in FSH and E2 production are due to the severely depleted
Follicles
Evidence shows that inhibin B levels are reduced in
Perimenopausal women
Recall that inhibin B is secreted by GC and suppresses
FSH secretion
Therefore, without the normal influence of inhibin B, FSH secretion is relatively unimpeded. In the presence of elevated FSH, more follicular growth could occur during each cycle, but still only one follicle will be
Selected to ovulate
Secreted from the GC within small growing follicles and suppresses recruitment and reduces sensitivity of young follicles to FSH
AMH
Since the overall number of follicles is depleted, we see a decrease in the levels of
AMH
From a functional viewpoint, the loss of the counter-modulatory effect of AMH on recruitment may free-up the entry of some more of what few follicles remain into the growing cohorts, exacerbating
Follicular depletion
Undetectable by the time a woman enters the menopausal transition
AMH
Has been identified as a marker to predict the onset of Menopausal transition
AMH
Women in their 40s (and possibly early 50s) can undergo menses; however, oocyte viability is
Drastically compromised
In addition to the increased risk of fetal genetic abnormalities (e.g., aneuploidies), maternal complications during pregnancy, and fetal/neonatal death are significantly elevated in
Reproductively aged women
With less follicular development comes a lower level of
E2 and testosterone production
The disruption in ovarian steroidogenesis leads to menstrual irregularities due to a
Prolonged follicular phase
During menopause, the follicular reserve has been severely depleted and normal menstruation does not occur. The normal FSH:LH ratio is increased and we see a precipitous decline in
E2 production
Other postmenopausal occurrences can include an increase in the ratio of serum LDL:HDL, and atherosclerosis; markers of increased
Cardiovascular risk
Although not life-threatening, the loss of E2 production can also cause the psychologically disturbing problems of
Urinary incontinence, hot flashes, and night sweats
Hormone therapy can promote a favorable serum lipid profile in some women, but there are no data showing a beneficial effect of HT on reducing the risk of
Coronary heart disease
A general rule of thumb for administering hormone therapy to women who are candidates is
- ) with uterus: estrogen and progesterone
2. ) Without uterus: estrogen only
It has been reported that it is appropriate to recommend HT to women who are not at elevated risk for breast cancer and with normal
Venous thromboembolitic and CV disease risk
Current evidence does not support the use of estrogen + progesterone or estrogen alone for long-term prevention of
Chronic disease
How much testosterone do the ovaries produce per day?
approximately 300 ug
The overwhelming majority of testosterone secreted by the ovaries is converted to
E2
An androgen deficiency can occur in post menopausal women, and this lack of testosterone has been associated with decreased
Libido
Anything that disrupts the normal production of FSH and LH will cause disorders of the
Reproductive system
Normally, the circadian rhythm for GnRH secretion occurs in a pulsatile manner; defined by temporal changes in the amplitude and frequency of
GnRH release
Sustained elevation of GnRH will down-regulate the secretion of
FSH and LH
Sustained use of exogenous androgens, such as anabolic androgenic steroids will impair the neuroendocrine system in a similar fashion, and cause
Infertility in women and men
Affects approximately 6-20% of reproductive age women. As such, it represents the most common endocrine disorder affecting women of reproductive age
Polycystic Ovary Syndrome (PCOS)
Clinically defined by infertility resulting from oligomenorrhea (less than 9 cycles per year) and or amenorrhea
PCOS
Diagnosed by:
1) history of irregular menses and anovulation, with onset at puberty;
2) chemically measurable hyperandrogenemia (ovarian androgens including free and total testosterone; presence of hirsutism); and
3) exclusion of other hormonal pathologies which have similar clinical features
PCOS
Was historically named due to the presence of large follicular cysts within the ovaries
PCOS
Is the presence of follicular cysts required for the diagnosis of PCOS?
No
PCOS is now classified as a
Metabolic disease
What are the four different sets of criteria that can be applied for diagnosing PCOS?
1) Hyperandrogenism with chronic anovulation
2) Hyperandrogenism plus polycystic ovaries with ovulation
3) Chronic anovulation plus polycystic ovaries w/out hyperandrogenism
4) Chronic anovulation plus hyperandrogenism with polycystic ovaries
For our purposes, please recognize PCOS that is (arguably) most commonly a condition of
Hyperandrogenic anovulation
When present, the cystic follicles are in some undefined arrested stage of folliculogenesis, and as such, do not
Ovulate an oocyte
Women with PCOS are more often than not
Overweight w/ android distribution
Are hyperandrogenemic (elevated serum androgens: testosterone, DHT, and/or DHEA-S) and/or present with hyperandrogenism
Women with PCOS
