1
Q
How are hormones released (pathways) into the anterior pituitary and the posterior pituitary?
A
- Anterior pituitary – releasing hormones released into blood supply from hypothalamus → travel to Ant. Pituitary → releases another hormone into the body
- Posterior pituitary – nerves from hypothalamus release releasing hormone directly to central blood supply
2
Q
What hormones go through the anterior and posterior? Diagram.
A
3
Q
What are the 4 types of proteins?
A
AA derivatives, steroids, peptides, proteins
4
Q
What are the two amino acids that hormones are derived from? What hormones are derived from each?
A
- Amino Acid Derivatives
- Tyrosine → catecholamines
- Tryptophan → serotonin and melatonin
5
Q
Name 6 steroid hormones and what they are dervied from?
A
- Steroids
- Derived from cholesterol → progesterone, androgens, testosterone, aldosterone, cortisol
- Vitamin D: 7-dehyrocholesterol → cholecalciferol (Vitamin D3) via sunlight
6
Q
What are three drug types that modulate steroids hormones? What are their MOAs?? What can these be used for?
A
- Pharmacology
- Tamoxifen/raloxifene – antiestrogens for ER-positive breast cancer
- Aminoglutethimide/Anastrazole – aromatase inhibitor, blocks estrogen synthesis
- Premenopausal women – estrogen synthesis in ovary
- Postmenopausal women – estrogen synthesis in adipose tissue
- Flutamide/Bicalutamide – antiandrogens useful for prostate cancer
7
Q
Name some peptide hormones (4)
A
- Peptides – less than 50 amino acids
- TRH, oxytocin, ACTH, insulin
8
Q
Name some protein hormones (4)
A
- Proteins
- FSH, LH, TSH, hCG – highly conserved 92 AA unit
Note that these 4 are VERY VERY SIMILAR
9
Q
How are signals transduced from hormones? 3 pathways
A
Signal Transduction
- 7TM-GPCRs, Tyrosine kinases, Nuclear receptors
10
Q
Define negative feedback and what it does in terms of hormone regulation.
A
Negative Feedback
- Tight regulation of “hormonal homeostasis” that maintains hormonal levels in a tight physiological range
11
Q
Name two GnRH analogs and what they are used in. What are their MOAs?
A
- GnRH analogs
- Leuprolide/goserelin – used in prostate cancer
- MOA: analog binds → constant stimulation of ant. pituitary → desensitization → decreased testosterone/estrogen
- Leuprolide/goserelin – used in prostate cancer
12
Q
Name 2 antiestorgens, 2 aromatase inhibitors, 2 antiandrogens?
A
- Tamoxifen/raloxifene – antiestrogens for ER-positive breast cancer
- Aminoglutethimide/Anastrazole – aromatase inhibitor, blocks estrogen synthesis
- Premenopausal women – estrogen synthesis in ovary
- Postmenopausal women – estrogen synthesis in adipose tissue
- Flutamide/Bicalutamide – antiandrogens useful for prostate cancer
13
Q
Follicular phase
- What hormone is dominant?
- Is LH or FSH release more?
- What occurs to the endoemetrium?
A
- Follicular (Proliferation of the endometrial tissue) – estrogen dominant
- Increased pulsatile frequency of GnRH release favors LH release, but in lower concentrations
- Continuous release of a GnRH analogue → decreased release of LH, FSH
- Changes in endometrium
- Mitosis, thickening of stroma, growth of glands
- Increased pulsatile frequency of GnRH release favors LH release, but in lower concentrations
14
Q
Luteal phase
- What hormone is dominant?
- Is LH or FSH release more?
- What occurs to the endoemetrium?
A
- Luteal (Secretions by endometrial tissue) – progesterone dominant
- Decreased pulsatile frequency of GnRH release favors FSH release, but in higher concentrations
- Changes in endometrium
- Secretion from glands, edematous stroma, growth of endometrium inhibited
15
Q
What are the main steps in the ovarian cycle?
A
Primoridal follicles → recruitment → Follicular growth → selection of dominant follicle → ovulation → luteal phase → menstruation → pregnancy (if fertilized)
16
Q
What happens to the primordial follicles at the beginning of the ovarian cycle?
A
- Primordial follicles – goes through cycles of growth and apoptosis independent of FSH/LH
17
Q
What happens in the recruitment phase of the ovarian cycle? How many follicles are recruited? What hormones are low and high?
A
- Recruitment – FSH stimulates multiple (3 to 11) primordial follicles → primary follicles → antral (secondary) follicles
- At luteal-to-follicular transition, steroids (estrogen) and inhibin are low → high levels of FSH (high estrogen inhibits FSH release)
18
Q
What happens in the follicular growth phase of the ovarian cycle? What cells are stumulated? What hormones are high?
A
- Follicular growth – Increasing FSH → stimulation of granulosa cells → increased estrogen (estradiol) → growth
- LH stimulates Theca cells → production of androgens/testosterone from cholesterol → granulosa cells convert androgens to estrogen via aromatase (high estrogen increases LH release)
19
Q
What happens in the selection of dominant follicle phase of the ovarian cycle? When does it occur? What cells are stumulated? What hormones are high?
A
- Selection of the dominant follicle (cycle day 5 to 7) – estrogen/FSH induce FSH receptor expression on one of the developing follicle → granulosa proliferation → dominant follicle
- Also induces activation of VEGF → capillary bed formation (more blood flow) → more FSH reaches dominant follicle
- FSH also induces LH receptors on granulosa cells
20
Q
What happens in the ovulation phase of the ovarian cycle? What is synthesized and what does this lead to? What happens to the follicle as a result?
A
- Ovulation – due to LH surge (can also be seen as an increase in temperature due to progesterone release)
- Synthesis of collagenases and prostaglandins → thinning of follicular wall and contraction of smooth muscle around follicle → dominant follicle ruptures and releases oocyte
- Remaining follicle → corpus luteum → production of progesterone and drop in estrogen
21
Q
What happens in the luteal phase of the ovaian cycle? What is inhibited/activated? What occurs if there is no fertilization?
A
- Luteal phase (14 days)– the production of hormones (progesterone, estrogen, inhibin) by corpus luteum by LH stimulation
- Inhibin inhibits both FSH and LH
- If no fertilization, corpus luteum after 9 to 11 days → corpus albicans
22
Q
What happens during the menstruation phase of the ovarian cycle? How long does it last? What are the hormone levels?
Does the follicular phase or luteal phase vary?
A
- Menstruation – last about 3 to 5 days
- Decrease in estrogen and progesterone levels → menstrual shedding of endometrium
- Cycle lengths vary due to variation in length of follicular phase
23
Q
What occurs during pregnancy? Why do you not get menses (what happens to the hormones)?
A
- Pregnancy (fertilization of oocyte by sperm) – results in rescue of corpus luteum
- Production of Human chorionic gonadotropin (hCG) – molecule similar to LH
- Stimulates the corpus luteum to produce progesterone and estrogen
- No fall in E + P → No menses
- Production of Human chorionic gonadotropin (hCG) – molecule similar to LH
24
Q
What is the cervix response to estrogen?
A
- Mucous production
- Estradiol
- Thin, watery mucous
- Glairy “raw egg white”
- Facilitates sperm progression
- Ferns on microscope slide
- Estradiol
25
What is the cervix response to progesterone?
* Mucous production
* Progesterone
* Thick, white, opaque mucous
* Inhibits sperm penetration
* Ac ts as barrier to pathogens
26
Enjoy this graph. Memorize it. Love it. Do whatever you want to it.
27
For cervical squamous cell carcinoma:
* What is the epidemiology?
* What is the etoiolgy (specify what types)?
* What is the presentation?
**Cervical Squamous Cell Carcinoma**
* Epidemiology:
* Ages 40-50
* Most pre-invasive lesions do not become invasive cancers → 30% of invasive cancers lead to mortality
* Cervical cancer is the 4th most common cancer in the world
* Etiology: HPV (dsDNA virus)
* HPV types 6 and 11 (LR-HPV): associated with low oncogenic risk (genital warts/condyloma)
* HPV types 16, 18, 31, and 33 (HR-HPV): associated with cancer and pre-invasive lesions
* Presentation: vaginal bleeding, cervical discharge
28
For cervical squamous cell carcinoma:
* What is the pathophys?
* What is the natural history?
* What are the risk factors?
**Cervical Squamous Cell Carcinoma**
* Pathophysiology
* HR-HPV → produces E6 and E7 → inhibition of tumor suppressor genes → uncontrolled cell proliferation
* E6: inhibits p53
* E7: inhibits RB-E2F, p53, p21
* Natural History
* Transient infection: usually clear within 1-3 years (self-limiting)
* LSIL tends to be transient
* Persistent infection: HR-HPV DNA integrates into host DNA → malignant transformation → 30% risk of developing high grade squamous intraepithelial lesion (HSIL) → untreated → invasive cancer
* Risk Factors for Carcinogenesis: tobacco, immune suppression
29
What is this? Name it and describe it.
* Squamous intraepithelial lesions (pre-invasive) of cervix
* Low-grade squamous intraepithelial lesion (LSIL)
* Micro: On top of epithelial layer, dysplasia is noted; however, normal N/C ratios at top (mature cells with lots of clear cytoplasm - koilocytes)
30
What is this? Name it, define it, and describe it.
* Squamous intraepithelial lesions (pre-invasive) of cervix
* High-grade squamous intraepithelial lesion (HSIL)
* Definition: any moderate/sever dysplasia or in-situ carcinoma
* Micro: On epithelial layer, dysplasia is noted widely (top to bottom); N/C ratios are high throughout
31
What is this? Name it and describe it?
* Invasive carcinoma of cervix
* Gross: tan mass
* Micro: irregularly shaped nest of malignant squamous cells with keratinization infiltrating stromas (see pic)
32
What is this? Name it and describe it.
* Gross: acetowhite lesions related to squamous intraepithelial lesions
33
How do you screen/prevent for cervical SCC? What is the gold standard?
* Pap smear – gold standard (sample of most superficial layer of transformation zone)
* Vaccinations: available for HPV, but not effective against established infections and duration of protection is unknown
34
What is this? Describe it and what does it show?
* Normal pap smear: Normal N/C ratios with one nucleus (pic)
* Most mature cells (pink cytoplasm), less mature cells (blue cytoplasm)
35
What is this? Describe it and what does it show?
* LSIL pap smear: koilocytes with abnormal/multiple nuclei and still lots of cytoplasm (pic)
36
What is this? Describe it and what does it show?
* HSIL pap smear: high N/C ratio with multiple nuclei per cell (pic)
37
Know the screening guidelines for cervical scc of all ages and of different histories!
* Age \< 21 y/o: No screening
* Age 21 to 29: cytology (pap smear) alone every three years
* Age 30 to 65: cytology and HPV co-testing every 5 years preferred
* Age \> 65 y/o: No screening after adequate prior negative screening
* Hx of HSIL or CA: continue annual screening for 20 years in women with hx
* After hysterectomy: no screening
38
What is the blood supply involved in penile erection? Two arteries.
* Blood supply
* Pudendal a. supplies the corpus cavernosum
* Dorsal a. supplies the urethra
39
What is the innervation during a penile erection?
* Peripheral
* Sympathetic
* Nerve roots
* Pathway
* Function
* Parasympathetic
* Nerve roots
* Pathway
* Function
* Innervation
* Peripheral Nerve: Dorsal nerve → sensation
* Autonomic Nerves (\*\*Point and Shoot)
* Sympathetic: T11-L2
* Lumbar splanchnic nerves → inferior mesenteric/superior hypogastric plexuses → pelvic plexuses
* Function: detumescence (flaccidity), orgasm, and ejaculation
* Parasympathetic: S2-3
* Pelvic splanchnic nerves → pelvic plexus + superior hypogastric plexus → cavernous nerves
* Function: tumescence (erection), orgasm, and ejaculation
40
Explain the physiology of an erection. Very detailed
* Dilation of arterioles and arteries by increased blood flow
* Trapping of incoming blood by expanding sinusoids
* Compression of subtunical venous plexus between tunica albuginea and peripheral sinusoids reducing venous outflow
* Stretching of the tunica which occludes emissary veins between the inner and outer layers
* Increase PO2 and intracavernous pressure (full erection)
* Contraction of ischiocavernosus muscle (rigid erection)
41
What neuro transmitters are involved in flaccidty/detumescence?
* Flaccidity and detumescence:
* Alpha adrenergic fibers releasing norepinephrine at the cavernous arteries
42
What neuro transmitters are involved in erection?
* Erection
* Nitric oxide (NO) released from nonadrenergic/noncholinergic (NANC) nerve endings as well as from vascular endothelium
* Boosts cGMP which relaxes the cavernous smooth muscle (Viagra works here)
43
What NT are involved in modulation of an erection?
* Modulation
* Acetylcholine modulates response by inhibiting alpha adrenergics and promoting NO release
44
What are organic causes of erectile dysfunction (4 groups with different disease/injuries in each group)?
* Organic
* Vasculogenic: arteriogenic (trauma), cavernosal (venous leak)
* Neurogenic: spinal cord injury
* Anatomic: Peyronie’s disease
* Endocrinologic: diabetes
45
What are psychogenic causes of erectile dysfunction?
* Generalized (general depression/anxiety), situational (about the idea of having intercourse)
46
What are the hormonal reasons for having erectile dysfunction?
* Hormone status
* Hypogonadism (reduced testosterone)
47
What are risk factors for ED? include meds
* Risk factors of ED: increasing age, psych disorders, CV dysfunction, diabetes, poor SES, smoking
* Meds: antihypertensives, psych meds, antiandrogens, opiates, alcohol, tobacco
48
Split up causes of ED into CNS/PNS/vascular in terms of diagnosis
* Diagnostic view of ED
* CNS: issue with arousal
* Situational anxiety, lack of interest, Parkinson’s, stroke, low testosterone
* PNS: issue with transmission of message through nervous system
* Diabetes, prostate surgery/pelvic fx (damages nerves)
* Vascular: damaged vessels in perineum
* PVD, diabetes, smoking, trauma, radiation, HTN, Peyronie’s, cycling
49
What are examples of PDE-5 inhibitors uded in ED. Know three drug names and their brand names.
* Phosphodiesterase-5 inhibitors (amplifies the message)
* Examples: sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra)
50
What is the MOA of PDE-5 inhibitors
* MOA: inhibits PDE5 → inhibits conversion of cGMP to 5 GMP → increases the levels of cGMP → smooth muscle relaxation → vasodilation
51
What are the SE of the PDE-5 inhibitors. Know SE for each one. Know if short acting or long acting.
* SE (all contraindicated with nitrates due to risk for severe hypotension)
* Sildenafil (short-acting): visual disturbances, headaches
* Tadalafil (long-acting) headaches all day, myalgias
* Vardenafil: contraindicated with antiarrhythmics
52
How do injectable prostaglandins work?
* Injectable prostaglandins (bypasses message system → directly activates)
* Inject prostaglandin into corpora cavernosa → direct vasodilation
53
What is the last resort treatment for ED
* Implanted penile prosthesis (last resort)
54
What are normal and abnormal bleeding patterns in a woman?
* Think length of cycle, length of menstruation, volume of blood
* Normal bleeding patterns
* Cycle length: 21-35 days, length of menstruation: ~7 days, Vol: 30-60 mL
* Abnormal bleeding patterns
* Vol: 80 mL (excessive)
55
What are the etiology groups of uterine bleeding?
PALM-COEIN
* Structural
* Polyp
* Adenomyosis
* Leiomyoma
* Malignancy
* Non-structural
* Coagulopathy
* Ovultory dysfunction
* Endometrial (aka endometritis)
* Iatrogenic
* Not yet classified
56
What etiology of abnormal uterine bleeding is this? Descirbe the gross pathology of this? Describe what you see here.
* **P**olyp (Endometrial polyp)
* Pathology
* Gross: sessile mass projecting into the endometrial cavity
* ]Micro (see pic)
* Thick walled blood vessels
* Dilated “out of sync” endometrial glands
* Neoplastic fibrous stroma
57
What do you see here? Decribe and name it. What would the gross pathology look like? What is the presenation of this disease?
* **A**denomyosis
* Pathology
* Gross: bulging mass in myometrium with trabecular cut surface
* Micro: abnormal endometrial glands and stroma deep within the myometrium (see pic)
* Surrounded my normal smooth muscle
* Presentation: pelvic pain, menorrhagia, dyspareunia, bleeding
58
What is this? Describe the gross pathology. What kind of person gets these lesions and what are they sensitive to?
* Leiomyoma (aka fibroid)
* Description: very common benign smooth muscle tumor sensitive to hormones (multiple lesions); common in pre-menopausal women
* Pathology:
* Gross: well-defined bulging white/tan mass (see right pic)
59
What is this? Describe the micro pathology. What kind of person gets these lesions and what are they sensitive to?
* Leiomyoma (aka fibroid)
* Description: very common benign smooth muscle tumor sensitive to hormones (multiple lesions); common in pre-menopausal women
* Pathology:
* Micro: spindle cells (see left pic)
60
What is this? Describe the micropathology? What would the gross pathology look like? Describe the disease.
* Leiomyosarcomas
* Description: rare, malignant single-lesion smooth muscle tumor in myometrium; seen in post-menopausal women
* Pathology:
* Gross: poorly-defined, invasive grey/yellow mass
* Micro: atypia, hypercellularity, multiple mitotic figures (see left pic)
61
Under **M**alignancy, is endometrial hyperplasia:
* Describe it.
* Risk factors?
* Epidemiology?
* Endometrial hyperplasia (precursor lesion to cancer)
* Description: exaggerated proliferation of glands of irregular size and shape with an associated increased gland to stroma ratio due to unopposed estrogen stimulation
* Risk Factors: obesity, PCOS, and diabetes (secondary to unopposed estrogen)
* Epidemiology: post-menopause bleeding
62
What is this? Describe the micro? What is the malignant potential
* Endometrial Hyperplasia without atypia
* Micro: crowded, irregular shaped glands made up normal N/C ratio; epithelium remain stratified columnar (see left pic)
* Malignant potential: 3-4 fold increase risk
63
What is this? Describe the micro? What is the malignant potential
* Endometrial hyperplasia with atypia (aka Endometroid intraepithelial neoplasia/EIN)
* Micro: high N/C ratio, prominent nuclei, crowded irregular gland (must compare to normal adjacent epithelium) (see left pic)
* Malignant potential: 14-45 fold increase risk
64
Under **M**alignancy, is endometrial carcinoma:
* Describe it.
* Epidemiology?
* Two types?
* Endometrial carcinoma
* Description: most common malignant proliferation of endometrial glands
* Epidemiology: post-menopausal bleeding
* Types
* Type I: Endometroid, mucinous, secretory
* Type II: Serous, clear cell
65
For type I endometrial carcinoma:
* Types?
* Epidemiology?
* Etiology (genes)
* Pathophys?
* Prognosis?
* Type I: Endometroid, mucinous, secretory
* Epidemiology: younger, obese, unopposed estrogen, insulin resistance
* Etiology: PTEN, MLH1, kras, MSI
* Pathophysiology (classical pathway – estrogen excess): endometrial proliferation → non-atypical hyperplasia → EIN → endometroid carcinoma
* Prognosis: good prognosis
66
For type II endometrial carcinoma:
* Types?
* Epidemiology?
* Etiology (genes)
* Pathophys?
* Prognosis?
* Type II: Serous, clear cell
* Epidemiology: older, black people, hx of breast CA
* Etiology: p53, HER2, PIK3CA
* Pathophysiology (alternative pathway – no estrogen excess): endometrial atrophy → intraepithelial carcinoma → serous invasive carcinoma
* Prognosis: poor
67
What is this? Describe the micropathology.
* Type I: Endometroid, mucinous, secretory
* Micropathology: hyperplasia with atypia that invades myometrium (looks similar to normal endometrium) (see left pic)
68
What is this? Describe the micropathology.
* Type II: Serous, clear cell
* Micropathology: non-circular papillary glands with bumpy linings (see pic to the right)
69
Explain some **C**oagulopathy causes of abnormal uterine bleeding.
* **C**oagulopathy
* Examples: Von Willebrand Disease, thrombocytopenia, coagulation factor deficiencies, hemophilia is rare (b/c x-linked)
70
Explain some **o**vulatory dysfunction causes of abnormal uterine bleeding.
* What are physiologic and pathologic states that you cang get anovulaton or oligo-ovulation?
* **O**vulatory Dysfunction
* Description: anovolulation or oligo-ovulation caused by:
* Physiologic: adolescence, perimenopause, pregnancy/lactation
* Pathologic: thyroid disease, hyperandrogenic state (i.e. PCOD), hyperprolactinemia, hypothalamic dysfunction, premature ovarian failure
71
What are some **I**atrogenic causes of abnormal uterine bleeding?
* **I**atrogenic
* Causes: IUDs, meds, radiation/chemotherapy
* Meds: gonadal steroids (estrogen, androgens), steroid related therapy (SERMs, GnRH analog), anticoagulants
72
What are some **N**ot yet classified causes of abnormal uterine bleeding?
* **N**ot yet classified
* Examples: arteriovenous malformation, Müllerian anomalies
73
What do you do look for history, PE, labs, and imaging when abnormal uterine bleeding is ocurring
* History: bleeding patterns, GynHx, SurgHx, meds, weight gain/loss, nipple d/c
* PE: Look for bruises, hirsutism, acne, acanthosis, thyroid issues, pelvic mass, vaginal issues
* Labs: pregnancy test, CBC, TSH, prolactin, pap smear, STD testing, coag studies
* Imaging: US, sonohysterogram, MRI, hysteroscopy
74
When do you get pathologic sampling/biopsy in abnormal uterine bleeding?
* Pathologic sampling
* Indicated in: women \>45 or women with \<45 with risk factors
75
What are consequences of abnormal uterine bleeding?
* Consequences: anemia, quality of life, hyperplasia, cancer
76
Define endometrisis. What is the most common site? What is the inheritance?
* Definition: presence of endometrial glands and stroma at extrauterine site
* Ovaries are the most common site
* Genetics: polygenic, multifactorial inheritance
77
What are the 4 theories of endometriosis? What is the evidence for each?
* Retrograde menstruation: endometrial cells enter peritoneal cavity via retrograde flow
* Evidence: disease seen in ovaries (presents as painful nodules)
* Vascular/lymphatic dissemination: transportation of endometrial cells via vessels/lymphatics
* Evidence: disease seen in lymph system (distant sites)
* Coelomic metaplasia: cells in the peritoneal cavity can change to functional endometrial tissue
* Evidence: presence of endometriosis prior to menarche
* Stem cells: stem cells from the endometrium differentiate into endometrial tissue
* Evidence: presence of endometriosis after placing stem cells in animal
78
What is the clinical presentation of endometriosis? What are some classical things?
* Clinical presentation: may be asymptomatic, adhesions/pelvic scarring
* Classic: progressive dysmenorrhea (starts 1-2 days before menses) with deep dyspareunia
* Others: pelvic pain (chronic), bowel issues, infertility, urinary sx
79
What can infertility in endometriosis be caused by in terms of disease progession?
* Infertility can be caused by:
* Extensive disease: distortion of fertile anatomy
* Minimal disease: presence of cytokines/autoantibodies/ prostaglandins → hostile environment for pregnancy
80
What is seen on pelvic exam of endometriosis?
* Pelvic exam: uterosacral nodularity is classic (rare), ovarian mass, retroverted uterus
81
When is expectant treatment for endometriosis indicated?
* Expectant treatment
* Indicated for: pregnant women, mild symptoms, older women awaiting menopause
82
What are 4 hormonal treatments for endometriosis?
OCP + NSAID (1st line), Progestin, androgen, GnRH
83
How does OCP treat endometriosis?
* OCP (plus NSAID): causes decidualization (change in endometrial tissue) → atrophy of endometrial tissue → less bleeding
84
How does Progestin treat endometriosis? Name some progestins
* Progestins (Depo Provera, IUD, Nexplanon/arm contraceptive): causes decidualization → atrophy of endometrial tissue → less bleeding and pain relief
85
How does androgens treat endometriosis? Name an androgen? Name some side effects
* Androgens (Danazol): suppresses LH/FSH surges → no estrogen production → endometrial atrophy/amenorrhea
* SE: acne, hot flashes, deepening of voice (not reversible)
86
Ho do GnRH agonists treat endometriosis? Name one. What are SE?
* GnRH agonist (Lupron): pituitary desensitization → downregulation of FSH/LH secretion
* SE: hot flashes, night sweats, decrease in bone density (can add progestin to avoid these)
87
What are surgical treatment for endometriosis?
* Surgical treatment
* Conservative: destruction/removal of visible lesions, normalization of anatomy
* Definitive: hysterectomy
88
# Define the following:
* Sexual orientation
* Gender identity
* Gender expression
* Sexual development
* Transgender
* Non-binary
* Difference of sexual dysfunction (DSD)
* Sexual orientation: physical and emotional attraction to same/opposite gender
* Gender identity: psychological identification as a man, woman, or other
* Gender expression: external characteristics/behaviors that are defined as masculine or feminine
* Sexual development: variations in sexual anatomy (aka intersex)
* Transgender: umbrella term describing state of person’s gender that does not match birth gender
* FTM: female to male (transgender male), MTF: male to female (transgender woman)
* Non-binary: having a gender that does not meet concepts of “all male” or “all female”
* Difference of sexual dysfunction (DSD): a person with sexual anatomy, reproductive organs, and/or chromosome patterns that do not fit the definition of male/female
89
What are 5 types of difference of sexual function?
* Difference of sexual dysfunction (DSD): a person with sexual anatomy, reproductive organs, and/or chromosome patterns that do not fit the definition of male/female
* Congenital development of ambiguous genitalia (clitormegaly, micropenis),
* Congenital disjunction of internal and external sex anatomy (5-alpha reductase deficiency),
* Incomplete development of sex anatomy (vaginal agenesis; gonadal agenesis
* Sex chromosome anomalies (Turner Syndrome; Klinefelter Syndrome)
* Disorders of gonadal development (ovotestes)
90
What are challenges associated with in the LGBT community?
* Challenges of LGBT community
* More likely to: commit suicide, be homeless, get HIV/STD, be obese, have mental health issues, abuse alcohol/tobacco/drugs
* Less likely to: get preventative services for cancer, carry health insurance
91
What are three diseases that the LGBT community is more likely to get? Why? And what group?
* Cervical cancer
* Lesbians get pap smears less frequently, but are still at risk for woman-woman transmission (WSW)
* Breast cancer
* Lesbians get mammograms less frequently, but have more risk factors
* STIs:
* WSW: bacterial vaginosis, chlamydia, HSV-1, HPV, Trichomonas, Syphilis, HIV
* MSM (high risk): HIV, syphilis, gonorrhea, chlamydia, hepatitis A/B, HSV, HPV
92
What are the 4 factors that demonstrate gender dysphoria?
* Transgender health – physician role to help with transition
* Gender dysphoria (DSM V criteria)
* Strong and consistent cross-gender identification
* Persistent discomfort with birth sex
* Discomfort is not concurrent with intersex
* Disturbance causes clinically significant distress in life
93
What are treatment options for gender dysphoria?
* Changes in gender expression and role
* Psychotherapy
* Hormone replacement therapy
* Gender confirmation surgery
94
What are hormone replacement therapies in MTF and FTM transitions? Explain effects of each.
* MTF: anti-androgens, estrogens
* Estrogens: decreased hair loss, risk of thromboembolic events, increased CV disease, hyperprolactinemia, HTN, infertility
* FTM: androgens
* Cessation of periods, increased muscle mass, facial hair, deepening of voice, clitoral enlargement
* Others: spironolactone (testosterone antagonist), testosterone, estradiol, GnRH analog
95
What can you do for gender confirmation surgery?
* change breasts, external/internal genitalia, facial features,
96
* For vulvovaginitis:
* Definition
* Epidemiology
* Pathophys
* Symptoms
* Diagnosis
* Types
**Vulvovaginitis**
* Definition: inflammation of the vulva and the vagina
* Epidemiology: most frequent CC at PCP office for women
* Pathophysiology: imbalance of the normal vaginal ecosystem
* Normal: lactobacilli → produces lactic acid/H2O2 → maintains normal vaginal pH (3.8-4.2)
* Normal vaginal discharge: clear to white without odor
* Symptoms: abnormal vaginal discharge, itching, burning, odor, irritation
* Diagnosis: Hx of symptoms, physical exam findings of pain/vaginal discharge, testing
* Testing: vaginal pH, microscopical exam (KOH), amine/whiff test, NAAT, gram stain/culture
* Types: bacterial vaginosis, trichomonas, vaginal candidiasis, atrophic vaginitis, viral infection (HPV/HSV)
97
For bacterial vaginosis:
* Pathogenesis
* Risk factors
* Complications
* Diagnosis
* Pathogenesis: non-inflammatory overgrowth of anaerobic bacteria in vagina and/or decreased protective lactobacilli
* Microbiology: Gardnerella vaginalis, Mobiluncus species, Mycoplasma hominis
* Lactobacillus growth: increases with estrogen
* Risk factors: poverty, WSW, douching, smoking, lots of unprotected sex, abx
* Complications: pre-term delivery, endometritis, salpingitis/PID, recurrent UTIs
* Diagnosis: clue cells (epithelial cells with attached bacteria) on microscopy with few WBC
98
What is Amsel's criteria? What is it used for?
Used to diagnose bacterial vaginosis:
* Amsel’s criteria (3/4): grayish discharge, clue cells, + Whiff test, pH \> 4.5
99
What are the two treatments for bacterial vaginosis?
* For each, provide MOA, SOA, SE
* Tx (both cause NVD)
* Metronidazole (po, topical)
* MOA: inhibits nucleic acid synthesis → disrupts bacterial DNA → bacteriostatic
* SOA: anaerobes, protozoa, and microaerophilic bacteria
* SE: disulfiram reaction (no alcohol), metallic taste, CYP2C9 inhibitor (increases warfarin levels)
* Clindamycin (topical)
* MOA: binds 50s rRNA → inhibits translocation → bactericidal
* SOA: gram positive bacteria and anaerobes
* SE: pseudomembranous colitis (C. Diff)
100
For trichomoniasis:
* Definition
* Signs
* Complications
* Diagnosis
* tx
**Trichomoniasis**
* Definition: motile (flagellated) anaerobic protozoan causing a vaginitis/STI
* Signs: frothy, green-yellow discharge with odor, pH \>4.5, strawberry cervix
* Complications: preterm birth
* Diagnosis: microscopic exam (motile trichomonas), copious WBC, NAAT
* Treatment: oral metronidazole (treat partners too), oral tinidazole
101
For vaginal candiadisis:
* Definition
* Sx
* Risk factors
* Diagnosis
* tx
**Vaginal Candidiasis**
* Definition: vaginal infection by C. albicans (90% of the time)
* Symptoms: odorless white discharge, burning sensation, pH \<4.5
* Risk factors: pregnancy, OCPs, abx, DM, HIV, steroids, cancer, thyroid disease
* Diagnosis: KOH (reveals pseudo-hyphae)
* Tx: OTC meds (miconazole, clotrimazole, tioconazole), prescription meds (fluconazole, butoconazole/terconazole)
* Self-treaters must come back if symptoms persist \>3 days
102
For atrophic vaginitis:
* Definition
* Sx
* Risk factors
* Diagnosis
* tx
* Description: lack of estrogen → thinning of vaginal tissue → inflammation
* Risk factors: menopause, lactation, oophorectomy, radiation therapy, chemotherapy, immunologic disorders, endocrine disorders, antiestrogen medications
* Symptoms: watery yellow discharge
* pH \> 6.0
* Absence of lactobacilli
* Wet Prep: numerous PMN’s; parabasal epithelial cells; background bacteria are cocci
* Treatment: vaginal lubricants and moisturizers; local or systemic estrogen
103
For desuqamative inflammatory vaginitis:
* Description
* sx
* tx
**Desquamative Inflammatory Vaginitis**
* Description: inflammation of the lining of the vagina (mucositis due to aerobic overgrowth)
* Symptoms: similar to atrophic vaginitis, but with: copious green-yellow frothy discharge, abundant WBCs, parabasal cells
* Treatment: clindamycin, topical hydrocortisone
104
For HSV STD
* Etiology
* signs/sx
* complications
* dx
* tx
* Herpes Simplex Virus
* Etiology: HSV 1 (oral), HSV 2 (genital) → live in dorsal root ganglion
* Signs/symptoms: painful multiple blisters, tingling pain, tender lymphadenopathy
* Complications: vertical transmission to fetus (can be prevented with C-section)
* Diagnosis: PCR, viral culture
* Treatment: acyclovir/valacyclovir/famciclovir
* Acyclovir MOA: acyclovir is converted to monophosphate and triphosphate by viral thymidine kinase → inhibits HSV DNA polymerase
105
For chancroid STD
* Etiology
* signs/sx
* dx
* tx
* Chancroid
* Etiology: Hamophilus ducreyi (a fastidious gram-negative coccobacillus)
* Signs/symptoms: painful single ulcer with gray necrotic base
* Diagnosis: chocolate agar
* Treatment: IM ceftriaxone, Azithromycin
106
For syphilis, generally explain:
* Etology
* Transmission
* Three stages
* Diagnosis
* Screening
* Tx:
* Syphilis
* General:
* Etiology: systemic disease caused by a motile anaerobic spirochete Treponema pallidum
* Transmission: direct contact of mucosa with lesion/transplancetally
* Three stages: Primary → Secondary → Latent → Tertiary
* Diagnosis: direct fluorescent antibody microscopy of lesion
* Screening:
* Non-treponemal tests: RPR (rapid plasma regain), VDRL (venereal disease research laboratory)
* Must confirm positive with treponemal tests: FTA-ABS, TP-PA, MHTA-TP (antibody tests to virus)
* Treatment: Penicillin G
107
Primary syphilis
* Description
* Sx
* Primary Syphilis
* Description: painless papule that ulcerates
* Symptoms (resolve in 3-6 weeks): mild lymphadenopathy
108
Secondary syphilis
* description
* sx
* Secondary Syphilis
* Description: popular eruption → condyloma lata
* Symptoms (resolves in 2-6 weeks): fever, sore throat, malaise, myalgia, weight loss, patchy alopecia, uveitis, lymphadenopathy
109
Latent syphilis
* Decsription
* Types
* Latent Syphilis
* Description: seroactivity without evidence of disease
* Types
* Early latent (within a year of symptoms)
* Late latent (greater than a year since symptoms)
110
Tertiary syphilis
* Types?
* Tertiary Syphilis
* Gummatous syphilis: soft tumor-like inflammatory balls affect skin, bone, liver
* Cardiovascular syphilis: aortitis
* Neurosyphilis: involves CNS → meningitis, menigovascular syphilis
* Seizures, Argyll Robertson pupils (non-reactive to light and does focus)
111
Chlamydia trachomatis
* Epidemiology
* Etiology
* Sx for each serotype
* Diagnosis
* tx
**Chlamydia trachomatis**
* Epidemiology: most frequently reported infectious disease in the US
* Etiology: gram negative obligate intracellular bacteria forms
* Symptoms:
* Sertoypes A-K: cervicitis, urethritis, trachoma (conjunctivitis from corneal abrasion), salpingitis/PID in untreated women
* Serotypes L1-L3 (Lymphogranuloma venereum): induce
* Primary: painless papule/ulcer
* Secondary: lymphoproliferative reactions → necrosis
* Tertiary stage: rectovaginal fistulas
* Diagnosis: NAAT or urinalysis (include Gonorrhea testing)
* Treatment: azithromycin, erythromycin, doxycycline
112
Gonorrhea
* Epidemiology
* Sx
* Diagnosis
* tx
**Gonorrhea**
* Epidemiology: second most reported infectious disease in the US
* Symptoms: green-yellow discharge, vaginal burning, dysuria, PID
* Diagnosis: NAAT, urinalysis, cervix swab (include Chlamydia testing)
* Treatment (aggressive): ceftriaxone plus azithromycin
113
For HPV STD:
* Description
* Etiology
* Tx (3 drugs)
* Explain MOAs
* Description: condyloma acuminata/genital warts
* Etiology: HPV 6 and 11
* Treatment:
* Warts are treated with cytosurgery, lase ablation, trichloacetic acid
* Infection is treated with:
* Cephalosporins (bactericidal): beta-lactam inhibiting transpeptidase → peptidoglycan cannot form
* Macrolides (bacteriostatic): binds to 50s ribosomal unit
* Tetracyclines (bacteriostatic): binds to 30s ribosomal unit
114
Physiology of control of testicular function (3 main hormones and functions)
* GnRH binds to a membrane receptor on pituitary gonadotrophs, and stimulates synthesis and secretion of FSH and LH
* Pulsatility of GnRH release is required for precision of signaling to pituitary
* FSH: Required for determination of the testicular Sertoli cell number and for induction and maintenance of spermatogenesis
* LH: stimulates the secretion of gonadal steroids through Leydig cell activity
115
Spermatogenesis
* Definition/location/length
* Phases and what occurs in each?
* Definition: process in which spermatozoa are produced from germ cells via mitosis/meiosis in seminiferous tubules (~ 2 months)
* Phases (periphery to inside)
* Proliferative phase – spermatogonia divide to
* replace their number (self-renewal)
* differentiate into daughter cells that become mature gametes
* Meiotic phase
* germ cells undergo a reduction division
* results in haploid spermatids
* Spermiogenesis phase
* spermatids undergo profound metamorphosis
* become mature spermatozoa
116
Pathway of ejaculation
* Seminiferous tubules → rete testis → efferent ducts → epididymal tubules → vas deferens → ejaculatory ducts → prostatic urethra
117
Failed spermatogensiss: Failure of GnRH secretion can be caused by what?
* Pituitary disorders (secondary hypogonadism) – decreased secretion of either LH or FSH
* Hypothalamic disorders (tertiary hypogonadism)
* Other
118
Name 2 pituitary disorders that cause failure of GnRH secretion leading to failed spermatogenesis
* Failure of GnRH secretion
* Pituitary disorders (secondary hypogonadism) – decreased secretion of either LH or FSH
* Isolated LH deficiency (fertile eunuch syndrome) – hypoandrogenism but production of viable sperm due to normal FSH
* Isolated FSH deficiency – normal androgenization (b/c normal LH) but no spermatogenesis
119
Name 1 hypothalamic disorder that causes failure of GnRH secretion leading to failed spermatogenesis
* Failure of GnRH secretion
* Hypothalamic disorders (tertiary hypogonadism)
* Kallman’s syndrome – anosmia (can’t smell) and possible undescended testes
120
What are three other causes of failure of GnRH secretion leading to failed spermatogensis?
* Failure of GnRH secretion
* Other
* Space-occupying lesion in the sella turcica – tumors in the anterior pituitary (prolactinoma – most common causes on infertility associated with decreased libido and headaches)
* Infection: granulomata infection, sarcoidosis, histiocytosis, hemochromatosis
* Systemic disease: obesity, malnutrition, diabetes
121
What are extrapituitary reasons for failed spermatogensis?
* Extra-pituitary endocrine modulators
* Exogenous androgen – testosterone negatively inhibits GnRH secretion
* Drugs: cannabis (decrease plasma testosterone), antipsychotics (dopamine antagonism), opioids (suppress LH release)
122
What are primary hypogonadism reasons for failed spermatogensis? What are the labs and give an example
* Primary hypogonadism – impaired testosterone synthesis caused by Leydig cell dysfunction
* Labs: elevated LH w/ decreased T (testosterone)
* Ex: Klinefelter syndrome (XXY) – most common cause of male hypogonadism
123
Testicular torsion:
* Clinical presenation
* PE
* Dx
* Tx
* Testicular torsion – twisting of the spermatic cords
* Clinical presentation: severe scrotal pain with rest, activity of trauma, N/V
* If presenting in neonates: perinatal testicular torsion
* PE: scrotal edema and erythema, absent cremasteric reflex
* Dx: Doppler US shows no blood flow
* Tx: orchiectomy, orchiopexy (w/in 6 hrs), contralateral orchiopexy
124
Torsion of appndages of testicles
* Epidemiology
* Dx
* Torsion of appendages – appendages on the testes or epididymis lose blood flow
* Epidemiology: most common cause of acute scrotum in ages 7-12
* Dx: Doppler US, blue dot sign
125
Epididymitis, epididymo-orchitis, orchitis
* Epidemiology
* Presentation
* PE
* Labs
* Dx
* Tx
* Epididymitis, epididymo-orchitis, orchitis – inflammation due to infection
* Epidemiology: men \< 35 – STI (Chlamydia/Gonorrhea); older men – BPH, UTI
* Presentation: gradual progressive onset of posterior testicular pain +/- fever
* PE: cremasteric reflex present, loss of rugae
* Labs: elevated WBC, UA shows bacteria
* Dx: Doppler US (normal to increased blood flow)
* Tx: abx, NSAIDS
126
Testicular tumor
* Epidemiology
* Labs
* Dx
* Tx
* Testicular tumor – painless testicular mass
* Epidemiology: most common solid malignancy among men 20-40
* Dx: US,
* Labs: AFP, hCG, LDH
* Tx: radical orchiectomy
127
For scrotal trauma, how do you diagnose it?
* Scrotal trauma – rupture due to laceration of tunica albuginea of testicle
* Dx: penetrating injury (exploration in OR), blunt force injury (work up via US)
128
Inguinal hernia
* Presentation
* Tyes and describe each
* Inguinal hernia – herniation of peritoneal structures into scrotum through inguinal canal
* Presentation: pain and swelling of scrotum and groin
* Types
* Incarcerated: irreducible hernia
* Strangulated: incarcerated hernia w/ no blood supply → pain → surgical emergency
129
For fournier's gangrene
* Epidemiology
* Preseantion
* PE
* Diagnosis
* Tx
* Fournier’s gangrene – acute necrotizing fasciitis of scrotum and groin
* Epidemiology: often seen in immunocompromised/diabetic patients
* Presentation: associated with cellulitis/abscess, pain and fever
* PE: diffuse enlargement, necrosis, crepitus
* Dx: US, CT-scan
* Tx: immediate debridement, broad spectrum abx
130
What is the optimal time for breast exam?
What do you do during PE?
When is a mammogram indicated?
What do you if palpable breast mass?
**Breast Examination**
* In pre-menopausal women – optimal time for exam is 7-9 days after onset of menses (lowered estrogen)
* PE: inspection → palpation of breasts → palpation of regional lymph nodes
* Mammograms: yearly screening after age 40, highly indicated for dense breasts
* If palpable breast mass: ultrasound for all ages with biopsy plus mammogram for 30+
131
Define carcinoma-in-situ
* Carcinoma in-situ: malignant proliferation of cells that has not breached the basement membrane
132
What are the risk factors for malignnt breast disease
* Risk factors for breast cancer: gender, age, genetic factors (BRCA1/2), menstrual period, post-menopausal hormonal therapy, non-breast feeding, obesity, alcohol, fat diet, smoking, lack of exercise
133
For intraductal papilloma
* Presentation
* Type of nipple discharge - compare to normal!
* Intraductal Papilloma – epithelial proliferation characterized by finger-like structures within ducts
* Presentation: 30-50 y/o with mass or nipple discharge, moderate increased risk for cancer
* Nipple Discharge
* Normal: green, yellow, white, grey, brown discharge (due to duct ectasia) or milky (lactation)
* Pathologic: clear or bloody
134
For fibroadenoma of breast
* Presentation
* Dx
* Complication
* Fibroadenoma – mobile/rubbery unilateral solid tumor that is hormone sensitive
* Presentation: younger women with nontender mass
* Dx: US hypoechoic, core biopsy
* Complications: may mask Phyllodes tumor
135
For breast abscess
* Presentation
* Dx
* Tx
* Types (what bugs cause each)
* Complication
* Breast abscess
* Presentation: pain, erythema, low-grade fever
* Tx: I&D, abx
* Dx: anechoic (black) with posterior enhancement on US
* Types:
* Sub-areolar abscess (most common) – caused by aerobes (Staph) and anaerobes
* Peripheral abscess – caused by aerobes (staph/group A strep)
* Complications: fistulas
136
For fibrocystic changes in breast
* Presentation
* Dx
* Complications
* Fibrocystic changes – dilated ducts
* Clinical presentation: 20-40 y/o woman with bilateral, lumpy-bumpy with blue domed cysts
* Responds to menstrual hormones (rare after menopause)
* Dx: spongy appearance on ultrasound
* Complications: may mask cancer
137
For invasive breast cancer:
* Clinical
* receptor types
* Dx of metastasis
* Tx (for each receptor type)
* Invasive carcinoma (ductal of lobular): invasion of basement membrane
* Clinical: tend to be multifocal, hard to detect by palpation or mammography
* Receptor types: ER+, PR+, HER2+ (poor prognosis)
* Dx: to check for metastasis, perform sentinel node biopsy
* Preferred over axial node biopsy because high rates of lymphedema
* Tx:
* Breasts: Lumpectomy + radiation OR mastectomy
* Systemic:
* SERM/Aromatase inhibitor (ER+)
* Chemo: Adriamycin/Cytoxan/taxane (ER-)
* Chemo + Trastuzumab (HER2+)
138
For ductal carcinoma in situ:
* Describe
* Presentation
* Types
* Labs
* Tx
* Ductal carcinoma in-situ
* Presentation: clusters of microcalcifications on mammogram
* Types: solid, cribriform, micropapillary, papillary
* Labs: usually ER+, PR+ possibly
* Tx:
* Breast conversing therapy: lumpectomy + breast radiation
* Mastectomy: if extensive disease
* Adjuvant therapy: SERM (selective estrogen receptor modulator) or aromatase inhibitor if ER+
139
For lobular carcinoma in situ:
* Describe
* Natural history
* Tx
* Lobular carcinoma in-situ: filling an expanding lobules by small uniform tumor cells
* Natural history: increased risk for invasive carcinoma
* Tx: observation OR observation + tamoxifen OR bilateral mastectomies
140
Trastuzamab
* MOA?
* SE?
* Trastuzumab (Herceptin) – MAB that binds to the extracellular domain of HER2 → inhibiting HER1 and HER2 dimerization → blocking cellular proliferation and angiogenesis
* SE: LV dysfunction → CHF, hypersensitivity, pulmonary toxicity
141
Aromatase inhibitor
* MOA?
* SE?
* Aromatase inhibitors – blocks conversion of androgens to estrogen
* SE: decreased bone density, joint pains, vaginal atrophy, hyperlipidemia
142
SERMS
* MOA?
* 2 examples?
* SE?
* SERMs – competitive inhibitors of estrogen binding to estrogen receptors on tumor tissue
* i.e. Tamoxifen, Raloxifene
* SE: hot flashes, endometrial hyperplasia/cancer, DVT, cataracts (due to agonist effects)
EndoRepro
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