Week 3 - “Breaking The Cycle” Flashcards
(286 cards)
1
Q
What is menopause?
Physiology
A
The permanent cessation of menstrual cycles following loss of ovarian follicular activity
2
Q
How is menopause confirmed?
Physiology
A
FSH levels > 25 IU/L
3
Q
What is a menopausal transition?
Physiology
A
Time between onset of irregular menses and permanent cessation of menstrual
4
Q
What is perimenopause?
Physiology
A
Also known as climacteric; period surrounding menopause characterised by fluctuating hormone levels, irregular menstrual cycles & symptom onset
5
Q
What is premature menopause?
Physiology
A
Cessation of menses prior to the age of 40, <40 primary ovarian insufficiency, 40 to 45: early menopause
6
Q
What is premature menopause associated with?
Physiology
A
Reduced risk of breast and ovarian cancers, but higher risk of CV disease and osteoporosis
7
Q
What is post menopause?
Physiology
A
All years following final menstrual period
8
Q
What are the types of menopause?
Physiology
A
Physiological/natural menopause
Iatrogenic (secondary) menopause
Primary Ovarian Insufficiency
9
Q
What are the different types of ioatrogenic menopauses?
Physiology
A
Removal of both ovaries (surgical)
Ovarian failure due to chemotherapy or radiotherapy, infection or rumor
10
Q
When does the menopausal transition begin?
Physiology
A
4 to 8 years before the final menstrual period
11
Q
What should women expect during the menopausal transition?
Physiology
A
Irregular menstrual cycles
Marked hormonal fluctuations
Hot flashes, sleep disturbances, mood symptoms and vaginal dryness
12
Q
What causes menopause?
Physiology
A
Exact cause is unknown but it may be due to combined dysfunction of the ovaries and the hypothalamus
13
Q
What is the ovarian dysfunction cause of menopause?
Physiology
A
Degeneration of granulosa and theca cells
Failure to react to endogenous gonadotropins
Decrease in estrogen
Increased in FSH & LH
14
Q
What are the neuroendocrine events that cause menopause?
Physiology
A
- Dysfunction in hypothalamic neurochemical signals involved in activating GnRH neurons
- This causes progressive impairement in timing of pre-ovulatory LH surge
- This adds to poor ovrain responsiveness
15
Q
What are the GnRH levels like in childhood and why?
Physiology
A
During childhood the hypothalamus does not secrete ssignificant quantities of GnRH, the hypothalamus is capable of secreting this hormone but the appropriate signal fromm other areas of the brain to cause the secretion is lacking
16
Q
Why is puberty caused in regards to hormones?
Physiology
A
Due to a gradual increase in the release of gonadotropins
17
Q
Why are FSH and LH (mainly FSH) produced after menopause in large quantities?
Physiology
A
To compensate for the declining estradiol levels due to the decrease in ovariann function
18
Q
At what point do the primordial follicles become atretic?
Physiology
A
When estrogen levels fall below zero
19
Q
What is estrogen secretion like during life?
Physiology
A
- Increased levels of estrogen during puberty
- Cyclic variation during the menthly sexual cycle
- Further increase in estrogen during the early years of reproductive life
- Progressive decrease in estrogen secretion toward the end of reproductive years
- ALmost no estrogen beyond menopause
20
Q
What is the relationship between FSH and estradiol/estrogen during a woman’s life?
Physiology
A
Tends to be opposite, when FSH is low, estradiol is normal and when etsradiol is highly variable estradiol is stable etc
21
Q
What are the effects of estrogen and progesterone on the anterior pituitary and hypothalamus?
Physiology
A
Both negative and positive effects depending on the stage of the ovarian cycle
22
Q
What is the purpose of inhibin?
Physiology
A
It has a negative e feedback effect by inhibiting FSH secretion by the anterior pituitary
23
Q
What determines the duration of ovarian functionality?
Physiology
A
Determined mostly by the extent and rapidity of oocyte apoptosis and follicle loss
24
Q
Which factors contribute to the decline in ovarian function and thus menopause?
Physiology
A
- Genetic factors
- Environment, lifestyle and diseases
- Interactions between neuroendocrine changes and alteration in the reprodcutive endocrine axis
- Hypothalamic aging and functional ovarian aging
25
How can genetic factors contribute to menopause?
| Physiology
Women whose mothers or other first degree relatives have had early menopause are 6 to 12 folds more likely to undergo early menopause themselves
26
How can hypothalamic aging contribute to menopause?
| Physiology
1. Desychronized GnRH secretion
2. Impaired timing of LH surge
3. Oestradiol fluctuation and decline
4. Anovulatory cycles and finally loss of menstrual cycle
27
What is the avarege age at which the follicular pool of primordial follicles runs out?
| Physiology
Around the age of 50
28
When does the first decline of primordial eggs happen?
| Physiology
Around the age of 35
29
What happens to menstrual cycle during early menopause transition?
| Physiology
Menstrual cycles become shorter and irregular --> follicular loss 10 years prior to menopause
30
What are the menstrual cycles of:
1. Premenopausal women
2. Perimenopausal women
3. Postmenopausal women
| Physiology
Premenopausal: regular menses
Perimenopausal: irregular menses for at least 1 year
Postmenopausal: no menses for at least 1 year
31
What is the relationship between anti-mullarian hormone and ovarian reserve?
| Physiology
AMH is secreted from the granulosa cells.
A decline in AMH means fewer small antral follicles are present to produce it.
With lower AMH, FSH-driven follicular recruitment increases (also secreted from granulosa cells), causing faster depletion of the ovarian follicular pool.
Eventually there will be a decrease in ovarian reserve --> menopause
32
What are the 3 main types of symptoms in women going through menopause?
| Physiology
Physical
Sexual
Psychological
33
What are the phsyical changes a woman goes through during menopause?
| Physiology
Episodes of flushing, sweating & intense warmth of uppoer body and face, skin temperature increases 1 to 7oC
It is then followed by chills
Psychic sensations of dyspnea
Itchy skin
Irregular HR
Breast pain
Digestive problems
Joint pain
Osteoporosis
34
What are the sexual changes a woman going through menopause might experience?
| Physiology
Irregular periods
Loss of libido
Vaginal dryness
35
What are the psychological changes a woman going through menopause might experience?
| Physiology
Irritability
Fatigue
Anxiety
36
What is the mechanism of hot flushes during menopause?
| Physiology
The mechanism is not knwon but it could be due to defect in the central thermoregulatory function, some estrogen-sensitive event in hypotalamus seems to indicate both LH and FSH release --> episode of flushing
Hot flushes coincide with the surges of LH but we know that LH is not responsible for the symproms, as tehy can continue past the removal of the pituitary
37
What are the studies' conclusions regarding the mechanism of hotflushes?
| Physiology
Flushes are preceded by an increase inn digital perfusion, followed by an increase in skin temperature (peripheral vvasodilation and increased blood flow)
Association with genetic, environmnetal, racial, lifestyle and hygiene factors
38
What are the 2 hypothalamic centers involved in thermoregulation?
| Physiology
1. Preoptic area of anterior hypothalamus (POA)
2. Posterior nucleus: heat-dissipating center
39
What is the mechanism with the preoptic area of anterior hypothalamus that is related to thermoregulation?
| Physiology
1. Neurons sensitive to heat changes (KNDy)
2. Activated neurons stimulate heat-loosing centers
3. During menopause --> hypothalamus becomes more sensitive to changes in the temperature
40
What is the mechanism of the posterior nucles (heat-dissipating center) that is associated with thermoregulation?
| Physiology
1. Vasodilation & sweating
2. Increased respiration through mouth
3. Inhibits heat-promoting center
41
What is the effect of estrogen on the KNDy?
| Physiology
Estrogen usually inhibits the neurons
42
What is the mechanism of regulation regarding estrogen and KNDy during menopause?
| Physiology
Estrogen levels drop, leading to:
1. Loss of inhibition on KNDy neurons.
2. Increased activity of NK3 receptors (NK3R), which are involved in temperature regulation.
3. KNDy neuron hypertrophy and increased signaling, leading to abnormal heat regulation.
43
What is Fezolinetant?
| Physiology
New FDA-approved drug:
Blocking NK3 receptors, reducing excessive KNDy neuron activity.
Restoring thermoregulatory stability, reducing hot flushes and night sweats.
44
What are the physiological changes that occur after menopause?
| Physiology
1. Ovaries and vasomotor changes
2. Endometrial thinning
3. Atrophy of urogenital tract & breast
4. Cardiovascular system changes --> more prone to CV disease
5. Bone weakening (osteoporosis)
45
What are the psychological changes that occur to women during menopause?
| Physiology
1. Mood changes, irritability, short-term memory loss
2. Interrupted sleeping patter & fatigue & depression
3. Loss of libido
46
What are the urogenital track changes that occur during menopause as a result of low estrogen?
| Physiology
1. Decreased vascularity --> decreased epithelial lining, increased fatty deposits, irritation, burning, itching and lack of lubrication
2. Vaginal atrophy --> increased tissue trauma and bleeding --> dyspareunia
3. Increased vaginal pH (from 4.5 to 7) leading to increased susceptibility to infection
4. Atrophic urethritis: urgency, frequency, suprabupic pain
5. Descent of uretus due to decreased collagen in uterosacral ligaments and cardinal ligament --> urinary incontinence
47
What is the relationship between estrogen and CV disease?
| Physiology
Estrogen is cardioprotective because it increases HDL and decreases LDL levels, increase in estrogen --> decrease in CV disease risk
48
What are the cardiovascular chnages that take place in women during menopause and why?
| Physiology
Post-menopausal women lack estrogen so their risk of developing CV disease increases;
1. Increased risk of atherosclerosis: increased total cholesterol (inceased LDL and decreased HDL)
2. Endothelial dysfunction
3. Increased androgens and truncal obesity and insulin resistance
49
How do menopause and ageing lead to obesity and what is the effect of that?
| Physiology
Increase in physical inactivity, mood instability and sarcopenia which result in obesity --> atherosclerosis --> ischemic ehart disease and stroke
50
What are the direct effects of menopausal estrogen decline on CV disease? What is the result of that?
| Physiology
1. Activation of RAAS
2. Increased angiotensin II
3. Increased endothelin 1
4. Decreased NO synthesis
--> These all lead to incresaed oxidative stress, vascular cell proliferation vascular wall inflammation, arterial stiffness and endothelial dysfunctiom
--> Atherosclerosis --> Ischemic heart disease and stroke
51
What are the indirect effects of menopausal ostrogen decline on Cv disease and what does that lead to?
| Physiology
1. Increase in visceral adiposity
2. Dyslipidemia: increased LDL and decreased HDL
3. Increased triglycerides
4. Increased insulin resistance
5. Increased BP
6. Chronic inflammation
--> These all increase the risk of atherosclerosis and thus ischemic heart disease and stroke
52
What is the relation between menopause and osteoporosis?
| Physiology
Up to 5 years after menopasue there is an accelerated loss of bone at the rate of 1 to 2% annually
25% of women who have osteoporosis by 60
53
What are three most common fractures at post-menopausal women?
| Physiology
Vertebrae, ultradistal radius and neck of the femur
54
What is the mechanism of osteoporosis in menopause?
| Physiology
RANK ligand whcih plays a crucial role in the osteoclastogenesis cascade
Estrogen suppresses RANKL and stimulates OPG production, helping to balance bone resorption and formation. Decrease in estrogen --> increase in expression of RANKL --> increase in osteoclast muturation and survival --> bone resorption > formation --.> osteoporosis
55
What are the immediate symptoms of menopause?
| Pharmacology
Vasomotor (hot flashes, sweating)
Insomnia
Decreased libido
Mood changes
Brain fogs
56
What are the intermediate symptoms of menopause?
| Pharmacology
Dyspareunia & vaginal dryness (thinning oof the vaginal mucosa --> atrophic vaginitis)
Urethral syndrome: dysuria, urgency and frequency
Incontinence, difficulty in voiding
Increased bruising
Generalized aches
57
What are some long-term symptoms of menopause?
| Pharmacology
Osteoporosis
CVD (coronary heart disease, dyslipidemia and stroke)
CNS --> Alzheimer's, dementia
58
What is MHT and what is used for?
| Pharmacology
Menopause hormonal therapy, used to augment the levels of hormones in the body
59
What are the different MHT options in regards to the presence of a uterus?
| Pharmacology
MHT involves estrogen alone in women who underwent hysterectomy
MHT includes both eestrogen and progestin in women with intact uterus, to decrease the amount of unopposed estrogen and thus endometrial cancer
Regardless HRT with estrogen shoud be used at the lowest dose possible and for the shortest duration
60
What is the first line of MHT?
| Pharmacology
Estrogen, unless there is a reason preventing it
61
What are the benefits of MHT?
| Pharmacology
Relieves vasomotor symptoms and vaginal atrophy
Helps with sleep disturbances, mood lability and even joint aches
Protects bone mineral density
Lowers the risk of CVD
Improves quality of lufe
62
What are the different drugs used for MHT? (5)
| Pharmacology
1. Estrogen (estradiol, conjugated and esterified estrogens)
2. Progestin
3. Androgen (Tibolone)
4. SERM
5. Tissue selective estrogen complex (TSEC): conjugated estrogen plus a SERM)
63
In which cases is Tibolone and androgen MHT important?
| Pharmacology
Hypoactive Sexual Desire Disorder due to decreased androgens
64
What are some non-hormonal drugs that are given for MHT?
| Pharmacology
1. Fluoxetine/paroxetine
2. Clonidene (ovulation induction)
3. Gabapentin
4. Fezolientant
5. Oxybutynin
65
What is the most prescribed non-hormonal drug for MHT? Why?
| Pharmacology
Fluoxetine/Paroxetine, it is a selective serotonin receptor inhibitor which helps suppress vasomotor symptoms
66
What is Fezolinetant?
| Pharmacology
First NK3 receptor antagonist to treat moderate to severe hot flashes from menopause --> MOA: binds to and blocks the activities of NK3 receptors, which play a role in the thermoregulation
67
What is Oxybutynin?
| Pharmacology
It is used to treat an overactive blasdder and urinary incontinence --> also effective for treating hot flashes
68
What are some non-pharmcological approaches to managing menopause symptoms?
| Pharmacology
1. Phsyical activity --> helps protect against aging, CVD
2. Strengthening pelvic floor muscles -> helps with incontinence
3. No smoking --> increases hot flashes and risk of early menopause
4. Decreasing vaginal discomfort (lubricant)
5. Cognitive behavioural therapy (mood swings etc.)
69
What is the parent hormone of estrogen (and all other steroids)?
| Pharmacology
Cholesterol
70
What are the sources of estrogen through-out a woman's life?
| Pharmacology
Premenopause: ovaries
Postmenopause: adipose tissue and adrenal cortex
Exogenous: contraceptives, hormone therapy, industrial (chemicals), phytoestrogen
71
When is systemic estrogen useD?
| Pharmacology
For women who are being treated for menopausal symptoms such as hot flashes (systemic)
72
When is low-dosage vaginal estrogen used?
| Pharmacology
For women being treated for genitourinary syndrome of menopause
73
What are the different types of estrogens for MHT?
| Pharmacology
Three main types of endogenous estrogen:
1. Estradiol
2. Estrone
3. Estriol
74
What is the purpose of estrogens in regards of MHT symptoms?
| Pharmacology
All typesa are effective for relieving hot flashes, when it comes to the frequency and the severity and also the duration
75
How does estrogen work in MHT?
| Pharmacology
1. All types of estrogen types work in concert with progesterone
2. Induce the synthesis of progesterone receptors
3. Decrease bone resorption
4. Increase retention of salt and water, and exert mild anabolic actions
76
What are examples of exogenous etsrogens used for MHT?
| Pharmacology
Mestranol
Ethinylestradiol
Diethylstilbestrol
77
What do the effects of the exogenous estrogens depend on?
| Pharmacology
Sexual maturity
78
What are the different MOAs of estrogens? (4)
| Pharmacology
Ligand-dependent
Tethered
Non-genomic
Growth factor signaling
79
What is the ligand-dependent MOA of estrogens?
| Pharmacology
Ligand attaces to nuclear estrogen receptor, dimerization occurs, move to nucleus --> activation of transcription factors
80
What is the tethered MOA of estrogens?
| Pharmacology
A substance is required between the receptor and the DNA
81
What is the non-genomic MOA of estrogen?
| Pharmacology
Receptor is not found in the nucleus or the cytoplasm but instead on the membrane itself, they act as G-coupling proteins.
Faster than all other MOAs
82
What is the growth factor signaling MOA of estrogens like?
| Pharmacology
It does not require estrogen for the estrogen receptors to be activated
83
What are the different administration routes for estrogen? (5)
| Pharmacology
1. Oral
2. Transdermal
3. Intramuscular
4. Implantable
5. Topical
84
What are the PK of estrogen?
| Pharmacology
1. Well absorbed orally, and from skin, and mucous membranes
2. Rapidly metabolized in the liver (synthetic degrade less rapidly)
3. Non-oral routes help reduce first-pass metabolism
4. Natural and synthetic estrogens are excreted in the urine
85
What is the MOA of progesterone in MHT?
| Pharmacology
Binds to nuclear receptors, estrigen stimulates synthesis of progesterone receptors wheateas progesterone inhibits synthesis of estrogen receptors only in some tissues like the endometrium --> progesterone contradicts estrogen
86
What are the functions of progesterone as part of MHT?
| Pharmacology
Inhibits ovulation
Reduces levels of FSH and LH
Stimulates osteoblasts --> reduced bone resorption
87
What some of the formulations of of synthetic progesterone? (5)
| Pharmacology
1. Desogestrel
2. Levonorgestrel
3. Norethindrone
4. Norgestrel
5. Medroxyprogesterone
88
What are the different routes of administration for progesterone?
| Pharmacology
1. Oral
2. Transdermal
3. Intramuscular
4. Implantable
5. Topical
89
What are the PK of progesterone?
| Pharmacology
1. Meatbolized very quickly by the liver --> if administered orally serum half-life is 5 minutes
2. Micronized progesterone is rapidly absorbed orally
3. Medroxyprogesterone acetate: oral half-life is 30 days, IM/IV half-life is 40 to 50 days, metabolized in intensinal mucosa and liver, excreted in urine and bile
90
What is the relationship between Estrogen Replacement Therapy and age?
| Pharmacology
Risks and benefits depedn on age:
women above 60: ERT increases the risk of MI and CHD
women 50 to 59: ERT somewhat protects against MI and CHD
91
Wha are the adverse effects of ERT? (8)
| Pharmacology
1. Endometrial cancer
2. Breast cancer
3. Ovarian cancer
4. Lung cancer
5. Dementia
6. Gallbladder disease
7. Urinary incontinence
8. Nausea, fluid retention, menstrual bleeding, acne/headache/depression
92
How does ERT increase the risk of endometrial cancer?
| Pharmacology
Estrogen increases the risk when given alone, thickening of endometrium and there is no progesterone to oppose its effect
Not given in women who have not had a hysterectomy
93
What is TESC?
| Pharmacology
Conjugated estrogen & selective estrogen receptor modulator --> a combination therapy --> has only been used for a short-period of time yet long-term risks are unknown
94
What are the contraindications of MHT? (8)
| Pharmacology
1. Suspected/current or past breast cancer
2. Endometrial cancer or other estrigen-dependent cancers (cervical etc)
3. Active or recent angine or MI
4. Venous thromboembolism
5. Uncontrolled hypertension
6. Acute liver disease
7. Pregnancy or breastfeeding
8. Abnormal vaginal bleeding
95
What liver diseases can estrogen be associated with? (7)
| Pharmacology
1. Intrahepatic cholestasis
2. Sinusoidal dilation
3. Peliosis hepatis
4. Hepatic adenomas
5. Hepatcellular carcinoma
6. Hepatic VTE
7. Gallstones
96
What is Tibolone?
| Pharmacology
Has estrogenic, progestogenic and weak androgenic activity
97
What is the purpose of Tibolone in MHT?
| Pharmacology
Short-term treatment for symptoms of estrigen deficiency
can be used continuously without cyclical progesterone
Helps relieve symptoms such as hot flashes, low mood and reduced sex drive
98
What are the adverse effects of Tibolone?
| Pharmacology
1. Abdominal/pelvic pain
2. Breast tenderness
3. Itching and vaginal discharge
99
Who is Tibolone not recommended for?
| Pharmacology
Women who have had breast cancer
100
What are uterine fibroids?
| Pharmacology
Uterine smooth muscale tumor (benign) --> unlikely to become cancer
they are not associated with a higher risk of other types of cancers in the uterus iether
101
When do uterine fibroids usually appear?
| Pharmacology
During fertile years --> may cause infertility depending on the type of fibroid
102
What do uterine fibroids generally present with?
| Pharmacology
Menstrual irregularities, menorrhagia, amenorrhea
103
What is the treatment for different types of uterine fibroids?
| Pharmacology
Small fibroids: hysteroscopy
Larger fibroids: laparoscopic myomectomy
Other options: UAE (uterine Artery Embolization)
104
What are possible pharmacological treatments for uterine fibroids?
| Pharmacology
GnRH antagonists
GnRH agonists
Progestin-releasing intrauterne device
Tranexamic acid
NSAIDs
105
What is the purpose and MOA of GnRH agonists?
| Pharmacology
MOA: initially cause gonadotrophin release but with prolonged use it causes desensitization of GnRH recptors in the pituitary
Block release of FSH and LH from anterior pituitary
Block production of estrogen and progesteronee
106
What are the adverse effects of GnRH agonists?
| Pharmacology
Decrease of estrogen so same as menopause symptoms
1. Flushing
2. Vaginal dryness
3. Bone loss due to hypo-estrogenism
107
What is the MOA of GnRH antagonists?
| Pharmacology
They block the GnRH receptors of the pituitary hence GnRH can not bind to it --> GnRH accumulates, downregulation of GnRH production --> decrease of FSH and LH production --> decrease in estrgen and progesterone
108
What are examples of Progestin-releasing IUD?
| Pharmacology
Levonorgestrel Intrauterine System
109
What is the purpose of Progestin-releasing IUD inthetreatment of fibroids?
| Pharmacology
Relieve heavy bleeding caused by fibroids, but do not shrink the fibroid
110
What is progestin-releasing IUD?
| Pharmacology
1. An intrauterine hormone delievry system
2. Once within uterus it causes endometrial atrophy
3. Licensed for HRT and also used as a contraceptive device
111
What is a normal side effect of progestin-releasing IUD?
| Pharmacology
Irregular bleeding is common in the first few months of therapy
112
In the case of conjugated equine estrogen vs transdermal estradiol which one should be chose and why?
| Pharmacology
Transdermal estradiol because it has less side effects
113
What is Tranexamic acid?
| Pharmacology
Non-hormonal medication: anti-fibrolytic
114
What is the MOA of Tranexamic acid?
| Pharmacology
Inhbits the coversion of plasminogen into plasmin and fibrin into its degenration products
--> Fibrin accumulates, blood clots --> decrease in menstruation heaviness
115
What is the purpose of Tranexamix acid when it comes to fibroids?
| Pharmacology
Helps ease heavy menstrual periods; taken only during heavy bleeding days
116
What are the potenetial side effects of Tranexamic acid?
| Pharmacology
Intravascular thrombosis due to antifibrolytic effects
117
What is the MOA of NSAIDs?
| Pharmacology
Blocks both COX-1 and COX-2 enzymes, prevents the production of prostaglandins --> less pain
118
What is the purpose of NSAIDs when it comes to fibroids?
| Pharmacology
Effective in relieving the pain caused by fibroids but do not shrink fibroids
119
What are examples of NSAIDs?
| Pharmacology
Ibuprofen
Naproxen
Mafenamic acid
120
What is Myfembree?
| Pharmacology
Relugolix, estradiol and norethindrone acetate: not first line but a once-daily treatment for heavy menstrual bleeding associated with uterine fibroids in PRE-menopausal women
121
What are the half-lives of Elagolix and Relugolix?
| Pharmacology
Elagolix: 5 hrs
Relugolix: 49 hrs
122
Why should estrogen therapy be taken at the lowest dosage and for the shortest duration possible?
| Pharmacology
Long-term estrigen is associated with incraesed risk for DVT, VTE
123
What is a contraindication of patients complaining of "MIGRAINES WITH AURA"?
| Pharmacology
Do not give estrogen, migraines with aura are associated with vascular dysfunction and estrogen enhances vasoconstriction --> increased risk of thrombosis and ischemic stroke
124
What does the pelvic brim divide?
| Anatomy
It divides the pelvis into false pelvis which is above the pelvic cavity and true pelvis which is below the pelvic cavity
125
What is the pelvic cavity?
| Anatomy
The area between the pelvic inlet and the pelvic outlet
126
What is the pelvic cavity subdivided by?
| Anatomy
By the pelvic diaphgrm into the main pelvic cavity above and the perineum below
127
What are the side walls of the pelvis formed by?
From hip bones clabbed with obturator internus and its fascia
127
What is the curved posterior wall of the pelvis formed by?
| Anatomy
Posterior curved wall is formed by the sacrum and piriformis muscle
128
What does the pelvic floor (pelvic diaphgram) consist of?
| Anatomy
COnsists of gutter shaped sheet of muscles:
1. Levator ani
2. Coccygeus
129
What are the support pelvic organs?
| Anatomy
Uterus
Bladder
Rectum
130
What are the contents of the pelvic cavity in both genders?
| Anatomy
The sigmoid colon and the rectum
131
What are the exact contents of the pelvic cavity in females?
| Anatomy
Rectouterine pouch which is filled with the coils of the ileum, sigmoid colon and outside the peritoneum uterus and fallopian tubes are related
132
What are the exact contents of the pelvic cavity of males?
| Anatomy
Retrovesical pouch which is filled with coils of the ileum, sigmoid colon and outside peritoneum, the bladder and seminal vesicles are related
133
What is the pelvic support of the uterus like? (4)
| Anatomy
The uterus is firmly fixed to the bladder and to the vagina
The pelvic diaphragm provides a supporting floor to the uterus
Condensation of visceral pelvic fascia (pelvic ligaments) strongly support the uterus
To a lesser extent the peritoneal attachments support to uterus
134
What is the uterus?
| Anatomy
Pear-shaped hollow organ with thick muscular wall that represents the site for pregnancy and implantation
135
What is the uterus divided into?
| Anatomy
The fundus
The body
The cervix
136
Where is the fundus of the uterus?
| Anatomy
Above the entrance of the uterine tubes
137
Where is the body of the uterus found?
| Anatomy
Below the uterine tubes
138
What is the cervix of the uterus?
| Anatomy
Narrow lower part which pierces anterior vaginal wall
139
Which cavity is associated with the cervix?
| Anatomy
Narrow cavity known as the cervical cavity
140
141
What are the clinical significances of the uterus communicating with the uterine cavity and teh vagina?
| Anatomy
1. Menstrual flow pathway
2. Sperm transport and fertilization
3. Pregnancy and labor
4. Infection pathways (ascending)
5. Role in uterine procedures (like hysteroscopy, endometrial biopsy and IUD)
142
What are the relations of the uterus?
| Anatomy
Anterior: uterovesical pouch and superior surface of bladder
Posterior: rectouterine pouch (douglas), coils of ielum and sigmoid colon
Lateral: uterine vessels (eithin broad ligament) ureters (below at cervix)
143
What is the blood supply to the uterus?
| Anatomy
Uterine artery which comes from the internal iliac artery
144
What is the position of the uterine artery?
| Anatomy
Runs medially within the broad ligament, reaches the cervix at right angle and above the ureter
145
What branch does the uterine artery give of?
| Anatomy
The vaginal branch, which is behind the ureter
146
Which artery does the uterine arter anastomose with?
| Anatomy
The ovarian artery
147
What are the ligamnets of the uterus? (5)
| Anatomy
1. The broad ligamnet
2. Cardinal ligament
3. Sacrocervical (uterosacral) ligament
4. Pubocervical ligament
5. Round ligament of the uterus
148
What is the broad ligament of the uterus?
| Anatomy
Double layer of visceral peritoneum that extends from one side of the pelvic cavity to the other and covers the uterus, tubes, ovaries and their associated ligaments
149
What is the broad ligament subdivided into?
| Anatomy
Mesosalpinx
Mesovarium
Mesometrium
150
What is the mesosalpinx?
| Anatomy
Upper edge that covers the uterine tubes
151
What is the mesovarium?
| Anatomy
It covers the ovaries and their round ligamenst
152
What is the mesometrium?
| Anatomy
It is the largest section, it covers the uterus, inferior to the mesosalpinx and the mesovarium
153
What is the location of the cardinal (transverse cervical) ligament?
| Anatomy
Lateral pelvic wall
154
Which structures are assocaited with the cardinal ligament?
| Anatomy
Cervix & upper end of vagina
155
Which ligaments are condensations of the pelvic fascia?
| Anatomy
The cardial ligament
The sacrocervical ligament
The pubocervical ligament
156
What is the sacrocervical ligament like?
| Anatomy
Ligament between the sacrum and the cervix, forms a ridge on each side of the Douglas pouch
157
What is the pubocervical ligament?
| Anatomy
Ligament between the pubic bone and the cervix, pass on each side of the bladder
158
What is the embryological origin of the round ligament?
| Anatomy
The gubernaculum
159
What is the round ligament like?
| Anatomy
Supralateral angle of the uterus, inguinal canal to subcutaneous tissue of labia majora
160
What is the function of the round ligament of the uterus?
| Anatomy
To keep the uterus anteverted (tilted forward) and anteflexed (bent forward)
161
What is the position of the uterus in regards to?
| Anatomy
Anteverted: bent relative to the long axis of the vagina
Anteflexed: bent relative to the long axis of the cervix
162
What is the retroverted uterus like?
| Anatomy
Fundus and body of the uterus are bent backward on the vagina and lie in the rectouterine pouch
163
What is the retroflexed uterus position?
| Anatomy
The long axis body of the uterus is bent backward on the long axis of the cervix
164
What is a prolapsed uterus?
| Anatomy
The descent of the uterus into or beyond the vaginal canal due to weakened pelvic floor support
165
What are the three layers of the wall of the uterus? (tunica terminology included)
| Anatomy
1. Tunica mucosa --> Endometrium
2. Tunica muscularis --> Myometrium
3. Tunica serosa --> Perimetrium
166
What is the parametrium?
| Anatomy
Dense regular connective tissue layer that surrounds the uterus outside the perimetrium. It is part of the broad ligament and serves as a supportive structure that contains important blood vessels, lymphatics, and nerves.
167
What is teh endothelial lining of the endometrium?
| Anatomy
Simple columnar epithelium containing secretory and ciliated cells
168
What is the lamina propria of the endometrium like?
| Anatomy
Loose connective tissue with many stellate fibroblasts
169
What are the uterine glands of the endometrium like?
| Anatomy
Simple tubular glands, covered by simplementation columnar epithelial cells
170
What are the layers of the endometrium?
| Anatomy
1. Zona functionalis
2. Zona basalis
171
What is teh zona functionalis of the endometrium like?
| Anatomy
More spongy and less cellular lamina propria
Richer in ground substance
Most of the length of the glands as well as the surface of the epithelium
172
What is the zona functionalis like during menstrual cycle?
| Anatomy
Exhibits dramatic changes during menstrual cycle every month as a result of hormonal changes, it is the layer that shed during menstruation
173
What is the zona basalis like?
| Anatomy
Basal layer adjacent to the myometrium
Contains highly cellular lamina propria and the deep basal ends of the uterine glands
174
What is the zona basalis like during the menstrual cycle?
| Anatomy
Undergoes very few changes during the mentrual cycle
175
What is the function of the zona basalis?
| Anatomy
Provides a new epithelium and lamina propria for the renewal of the endometrium
176
What is the blood supply of the endometrium?
| Anatomy
Unique dual blood supply; the uterine artery distributes the arcuate arteries in the middle layer of the myometrium so 2 sets of arteries arise to supply blood:
1. Straight basal arteries
2. Coiled spiral arteries
177
What are coiled-spiral arteries like?
| Anatomy
Progesterone-sensitive
178
What are vascular lacunae?
| Anatomy
Many dilated, thin-walled vessels that also supply the endometrium
179
What is the myometrium?
| Anatomy
Thick muscular layer (poorly defined layers)
It consists of inner longitudinal, middle circular and outer longitudinal layers
180
What does the middle circular layer of the myometrium contain?
| Anatomy
The larger blood vessels (arcuate arteries) --> stratum vasculare
181
What happens to the myometrium during pregnancy?
| Anatomy
Thickens during pregnancy because of the hypertrophy and hyperplsia of individual smooth muscle cells
182
What is the cervix like?
| Anatomy
Less muscular than the myometrium, the mucosa of the cervix does not undergo any changes during the menstrual cycle
183
What is the exocervix or vaginal portion of the cervix lined by?
| Anatomy
Stratified squamous epithelium
184
What is the endocervix, supra vaginal cervix portion lined by?
| Anatomy
Mucous sereting simple columnar epithelium which forms cervical glands
185
WHat is the purpose of the mucous secretion from the cervical glands of the cervix?
| Anatomy
They promote fertilization
186
What are some non-neoplastic disorders of the endometrium?
| Pathology
Endometritis
Adenomyosis
Endometriosis
187
What is Endometritis?
| Pathology
Inflammation of the endometrium
188
What are the classifications of endometritis?
| Pathology
Acute endometritis
Chronic endometritis
189
What is the characteristic of acute endomeritis?
| Pathology
Abnormal presence of polymorphonuclear leukocytes in the endometrium
190
What is the most common reasoning behind acute endometritis?
| Pathology
Ascending infection form the vahina or intestinal tract flora
191
What are the causes of acute endometritis?
| Pathology
Retained products of conception subsequent to miscarriage or delivery or to presence of foreign body such as IUD or tampons
192
What is the characteristic of chronic endometritis?
Abnormal presence of lymphocytes and plasma cells in the endometrium (lymphocytes are nomally found in the endometrium)
193
What are the causes of chronic endometritis?
| Pathology
retained products of conception, chronic pelvic inflmmatory disease (N. gonorrhea or C. trachomatis), IUD or TB
194
What are the clinical presentations of endometritis?
| Pathology
Fever, abdominal pain, and menstrual abnormalities
195
What are the clinical conswequences of endometritis?
| Pathology
Increased risk of infertility and ectopic pregnancy (due to damage and scarring of the fallopian tubes)
196
What is adenomyosis?
| Pathology
Presence of endometrial glands and stroma in the myometrium
197
What is the pathogenesis of adenomyosis?
| Pathology
Reactive hypertrophy of the myometrium --> enlarged globular uterus with a thackened uterine wall
198
What are the microscopic features of adenomyosis?
| Pathology
Glands lined by mildly proliferative to inactive endometrium and surrounded by endometrual stroma with varying degrees of fibrosis
Different degrees of glandular hyperplasia
199
What are the clinical features of adenomyosis?
| Pathology
Asymptomatic but:
1. Menorrhagia
2. Dysmenorrhea
3. Pelvic pain before onset of menstruation
200
What is endometriosis?
| Pathology
Presence of endometrial glands and stroma outside the uterus
201
What is the prevelance of endometriosis?
| Pathology
5 to 10% of women of reproductive years
nearly half of women with infertility
202
What are the sites of involvement with endometriosis?
| Pathology
1. Ovaries (60%)
2. Other uterine adnexa (uterine ligaments, rectovaginal septum, ouch of Douglas)
3. Less common: pelvic peritoneum covering the uterus, fallopian tubes, rectosigmoid colon and bladder
203
What are the three pathogenesis hypotheses of endometriosis?
| Pathology
1. The regulation tehory
2. The metaplastic theory
3. Lymphatic dissemination theory
204
What does the regulation hypothesis of endometriosis purpose?
| Pathology
Endometriosis occurs due to the retrograde flow of sloughed endometrial cells/debris via the fallopian tubes into the pelvic cavity during menstruation --> retrograde menstruation
205
What does the metaplastic theory of endometriosis purpose?
| Pathology
Endometrial differentiation of coelomic epithelium (mesothelium of the pelvis and abdomen from which the endometrium originates) is the source of endometriosis
206
What does the lympathic dissemination theory purpose?
| Pathology
Endometrial tissue from the the uterus can "spread" to distant sites via blood vessels and lymphatics
207
What are the gross features of endometriosis?
| Pathology
Functioning endometrium with:
1. red-brown nodules or implants
2. range in size from micrcopic to 1 or 2cm in diameter
3. Lie on or just under the affected serosal surface
4. FIbrosis: scarring; grossly brown discoloration
208
What are the features of endometriosis on the ovaries?
| Pathology
Lesions may form large, blood-filled cysts that turn brown as the blood ages
209
What are the microscopic features of endometriosis?
| Pathology
The histologic diagnosis depends on fidning two of the three features within the lesions:
1. Endometrial galnds
2. Endometrial stroma
3. Hemosiderin pigment
210
What do the clinical features of endometriosis depend on?
| Pathology
The distribution of the lesions
211
What are some clinical features of endometriosis?
| Pathology
Uterine ligaments --> pelvic pain
Pouch of Douglas --> dyschezia
Uterine serosa --> dyspareunia
Bladder serosa --> dysuria
Fallopian tube mucosa --> scarring increases risk of ectopic tubal pregnancy
In all cases there is severe ddysmenorrhea and pelvic pain
212
What is menorrhagia?
| Pathology
Profuse or prolnged bleeding at the time of the period
213
What is metrorrhagia?
| Pathology
Irregular bleeding between the periods
214
What is postmenopausal bleeding?
| Pathology
Bleeding after the cessation of menstruation for at least 12 months
215
What are the different causes of abnormal uterine bleeding?
| Pathology
Endometrial polyps
Leiomyomas
Endometrial hyperplasia
Endometrial carcinoma
Endometritis
216
What are the different categories of abnormal uterine bleeding?
| Pathology
1. Menorrhagia
2. MEtrorrhagia
3. Postmenopausal bleeding
217
What is endometrial hyperplasia?
| Pathology
Excess of estrogeb relative to progesterone (induce exaggerated endometrial proliferation)
precursor of endometrial carcinoma
218
WHat are the causes of endometrial hyperplasia?
| Pathology
1. Obesity
2. Failure to ovulation
3. Prolonged administration of estrogenic steroids without conterbalancing progestin
4. Estrogen-producing ovarian lesion
219
How is obesity a cause of endometrial hyperplasia?
| Pathology
Adipose tissue converts steroid precursors into estrogens
220
What are the classification of endometrial hyperplasia?
| Pathology
1. Based on architectural crowding (simple or complex) and the presence or absence of cytologic atypia
2. The risk of developing carcinoma is related to the presence of cellular atypia
3. Acquisition of PTEN mutations is one of the several key steps in the ransformation of hyperplasias to endometrial carcinomas
221
What is endometrial carcinomas?
| Pathology
Malignant proliferation of endometrial glands
Most frequent cancer occuring in the females gnital tract
222
What is the age of endometrial carcinomas?
| Pathology
Between 55 and 65, the uncommon age is around 40
223
What are the two types of endometrial carcinomas?
| Pathology
Endometroid carcinoma --> type 1 (most common, less serious)
Serous carcinoma --> type 2
224
What are the risk factors of type 1 (endometroid carcinoma)?
| Pathology
1. Obesity
2. Diabetes
3. HTN
Infertility
Exposure to unopposed estrogen
--> increased estrogenic stimulation of the sendometrium leads to endometrial hyperplasia
225
What is teh relationship between endometrial canecr and other cancers?
| Pathology
Higher incidence of both breast and ovarian cancer in closely related women, suggesting a genetic predisposition
226
What is the pathogenesis of type 1 endometroid carcinoma?
| Pathology
Mutations in misnatch repair genes and tumor suppressor gene PTEN
Women with germline mutation in PTEN (Cowden syndrome) and germline alterations in DNA mismatch replair gene (Lynch syndrome) are at high risk of this cancer
227
What is the pathogenesis of type 2 serous carcinoma?
| Pathology
Nearly all cases of serous carcinoma have mutations in the TP53 tumor suppressor gene
Serous tumors are preceded by a lesion called serous endometrial intraepithelial carcinoma (SEIC)
228
What is the morphology of endometrioid carcinoma?
| Pathology
1. Closely resemble endometrium and may be exophytic or infiltrative
229
What is the range of histologic types of endometrioid carcinomas?
| Pathology
Mucinous, tubal (ciliated) and squamous (occasionally adenosquamous)
230
Where do the endometrioid carcinomas originate from?
| Pathology
Originate in the mucosa and may infiltrate the myometrium and enter vascular spaces
231
What is the grading of endometrioid carcinomas?
| Pathology
Graded I to III, based on the degree of differentiation
232
What are the gross features of serous carcinomas?
| Pathology
Large hemorrhagic and necrotic tumor with deep myometrial invasion
233
What are the microscopic features of the serous carcinomas (endometrium) ?
| Pathology
Well formed papillae (thick and thin) appearance
--> Highly pleomorphic tumor cells (prominent nucleoli, small detached buds and tufts)
--> Severe cytologic atypia (gaps in between piplae )
234
What are the clinical manifestations of endometrial carcinomas?
| Pathology
Leukorrhea
Irregular bleeding (often in postmenopausal women)
235
How is endometrial carcinoma diagnosed?
| Pathology
Cervicovaginal cytologic screening is usuitable. for early detection
Transvaginal US is a valuable diagnostic modality ( > 5mm endometrial thickening --> highly suspicious)
236
How does endometrial cancer spread?
| Pathology
Directly to para-aortic lymph nodes, skipping pelvic nodes
237
What kind fo metastasis is common in patients with endometrial carcinomas?
| Pathology
Advanced cancers mat develop pulmonary metastases
238
What are endometrial polyps?
| Pathology
Monoclonal outgrowths of endometrial stromal cells altered by chromosoaml translocation (6p21) with secondary induction of polyclonal glandular elements
239
Where are large endometrial polyps located?
| Pathology
Larger polys may project from the endometrial mucosa into the uterine cavity
240
What is the age group of endometrial polyps?
Occur at any age, they are most common around the time of menopause
241
What is the clinical significance of endomerial polyps?
| Pathology
Abnormal uterine bleeding
Giving rise to cancer but it is very rare
242
What are leiomyomas? Where do they arise from?
| Pathology
Benign tumors that arise from the smooth muscle cells in the myometrium
Most common benign tumor in females
More frequent in blacks than in whites
243
What are the characteristics of Leiomyomas?
| Pathology
Monoclonal
Associated with several different recurrent chromosomal abnormalities (rearrangements of chromosome 6 and 12)
Mutations in the MED12 gene, which encodes a component of the RNA polymerase transition complex
Estrogen and OCP stimulate the growth of leiomyomas
244
What happens to leiomyomas during pregnancy?
| Pathology
They enlarge during pregnancy and shrink after menopause
245
What are the classifications of Leiomymas?
| Pathology
1. Subserous
2. Intramural
3. Submucous
246
What are subserous leiomyomas?
| Pathology
Located beneath the serosal surface, they grow out toward the peritoneal and can be sessile or pedunculated
May attach to adjacent structures (the bowel, omentum or mesentery) and develop a secondary blood supply
they may also extend into the broad ligamnet
247
What are intramural leiomyomas?
| Pathology
Most common type
Found primarily within the thick myometrium
248
What are submucous leiomyomas?
| Pathology
Asymptomatic, located beneath the endometrium
Associated with abnormal uterine bleeding
249
What are the gross features of leiomyomas?
| Pathology
Sharply circumscribed, firm-gray white mass (with no encapsulation)
May occur singly or multiple tumours (more common)
Ranging from small nodules to large tumors (1 mm to 30cm in diameter)
250
What are the microscopic features of leiomyomas?
| Pathology
Bundles of smooth muscle cells (mimicking the appearnce of normal myometrium)
251
What might leiomymas present with?
| Pathology
Foci of fibrosis
Calcification
Degenerative softening
252
What do the symptoms of leiomyomas depend on?
| Pathology
Can be influenced by the location, size or number of fibroids.
They are usually asymptomatic
253
What are some symptoms leiomyomas may present with?
| Pathology
Menorrhagia, with or without metrorrhagia
Pelvic pressure or pain
Frequent urination
Difficulty emptying bladder
Constipation
254
What is the association between leiomyomas and cancer?
| Pathology
They almost never transform into sarcomas and he presence of multiple lesions does not increase the risk of malignancy
255
What are leiomyosarcomas? Where do they arise from?
| Pathology
Malignant proliferation of the mesenchymal cells of the myometrium
256
How do leiomyosarcomas arise?
| Pathology
They arise de novo, not from leiomyomas
257
What is the traget population of leiomyosarcomas?
| Pathology
Postmenopausal women, accounts for 2% of uterine malignancies
258
What is the contradistinction between leiomyomas and leiomyosarcomas?
| Pathology
Leiomyomas are frequently multiple in number and arise in premenopausal women
259
What is the gross appearance of leiomyosarcomas?
| Pathology
Soft, hemorrhagic and necrotic masses
260
What are the microscopical features of leiomyosarcoma?
| Pathology
Tumor necrosis, cytologic atypia and mitotic activity (necesaary to make a diagnosis of malignancy)
261
What is the prevalence of tumors of the ovary?
| Pathology
8th most common cancer in the US. women
5th leading contributor to cancer mortality in women
262
What are the three cell types of tumors of the ovary?
| Pathology
The multipotent surface (coelomic) epithelium
The totipotent germ cells
The sex cord-stromal cells
263
Where does the vast majority of ovarian neoplasms arise from?
| Pathology
Coelomic epithelium that covers the surface of the ovary, embryologcially produces the epithelial lining of the fallopian tube (serous cell), endometrium and endocervix
264
What is the pathogenesis of surface epithelial tumors of the ovaries?
| Pathology
1. Repeated Ovulation and Scarring
With each ovulation, the ovarian surface epithelium undergoes disruption and subsequent repair.
This process increases the risk of epithelial entrapment in the ovarian cortex.
2. Formation of Epithelial Cysts
Some trapped epithelial cells form small cysts within the ovary.
These cysts can remain benign or undergo transformation into tumors.
3. Neoplastic Transformation (Metaplasia → Tumor Formation)
Over time, these epithelial cysts may become metaplastic or neoplastic, leading to the formation of:
Benign tumors: Cystadenoma, cystadenofibroma.
Malignant tumors:
Cystic tumors: Cystadenocarcinoma.
Solid tumors: Carcinoma.
265
What is the role of gonadoropins in the surface epithelium tumor progression?
| Pathology
After menopause, FSH and LH levels remain persistently high due to the loss of estrogen negative feedback.
These hormones stimulate the surface epithelial cells, promoting further genetic mutations and increasing the risk of carcinogenesis.
266
What are protective factors against ovarian tumors?
| Pathology
Pregnancy
OCPs
267
What are the risk factors for the sirface epithelial tumors?
| Pathology
1. Nullparity (no previous pregnancies)
2. Family history
3. Germline mutations in certain tumor suppressor genes (mutations in BRCA1 and BRCA2)
268
What are the most common subtypes of surface epithelium tumors?
| Pathology
1. Serous (full of water)
2. Mucinous (full of mucous-like fluid)
Both are usually cystic
Both can be benign, borderline or maliganant
269
Which subtype of ovarian tumors is most common?
| Pathology
Serous tumors
270
What is the malignancy of serous tumors like?
| Pathology
About 60% are benign, 15% are of low malignant potential and 25% are malignant
271
What is the target population of benign serous tumors?
| Pathology
Usually encountered in patients between 30 and 40 years of age
272
What is the target population of malignant serous tumors?
| Pathology
More commonly seen between 45 and 65
273
What is the pathogenesis of serous tumors?
| Pathology
Low grade: associated with KRAS, BRAF or ERBB2 mutations
High grade: associated with mutations in TP53
274
What is the gross apperance of serous tumors?
| Pathology
Serous cystoadenoma of the ovary: Wall is thin and translucent, clear fluid
275
What are the microscopic appearance of serous tumors?
| Pathology
SIngle layer of ciliated tubal-type epitehelium
276
What are the differences between serous type and mucinous type ovarian tumors?
| Pathology
Mucinous tumors have neoplastic epithelium which consists of mucin-secreting cells
Mucinous tumors are considerably less likely to be malignant
277
What is the pathogenesis of mucinous tumors?
| Pathology
KRAS mutations in early event in mucinous tumorgenesis
Overexpression/amplification of HER2 in mucinous carcinomas and mucinous borderline tumors
278
What is the morphology of mucinous tumors?
| Pathology
The tumor is characterised by numerous cysts filled with thick, viscous fluid
A single layer of mucinous epithelial cells lines the cyst
279
What is the prognosis of low-grade serous tumors?
| Pathology
Favorable
280
What is the prognosis of high-grade serous ovarian tumors?
| Pathology
Poor
281
What is the prognosis of clear cell, endometroid and mucinous tumors?
| Pathology
Clear cell: intremediate
Endometroid: Favorable
Mucinous: Favorable
282
What are mature teratomas?
| Pathology
Benign neopalsm that accounts for 1/4 of all ovarian tumors, peak incidence in the third decade
283
WHat is the pathogenesis of mature teratomas?
| Pathology
Mature teratomas develop by parthenogenesis, haploid germ cells endoreducplicate to give rise to diploid genetically female tumor cells
284
What is the morphology of mature teratomas?
| Pathology
They are cystic and almost all contain skin, sebaceous glands, and hair follicles
Half have smooth muscle, sweat glands, cartilage, bone, teeth and respiratory epithelium
Other tissues can also be present like gut, thyroid, brain but they are less often seen
285
