Exam 2 part 2 Flashcards
1
Q
Genetic sex
A
chromosomal makeup (XY or XX) The SRY gene is the genet hat shifts development away from female
2
Q
Gonadal sex
A
Presence of ovaries or testes
- Para-mesonephric (mullerian) duct- female, not fully connected
- Mesonephric (wolffian) duct- male, turns into wolffian duct in presence of testosterone
3
Q
Phenotypic sex
A
External or internal genitalia
Genital tubercle- develops into tip of penis or clitoris
Urogenital fold- seals and forms line of penis or labia
Labioscrotal fold- forms scrotum or labia
4
Q
Psychological sex
A
Sex the person identifies with
5
Q
sertoli cells
A
Secrete Mullerian-inhibiting substance (MIS) causing regression of the Mullerian ducts.
6
Q
Leydig cells
A
Secrete testosterone which acts on the Wolffian ducts to make the epididymis, vas deferens, seminal vesicles, ejaculatory duct
DHT makes penis, scrotum, prostate
7
Q
What merges the reproductive and urinary tracts in the male
A
Prostate
8
Q
What does sperm production require
A
Temperatures several degrees below normal body temperature (function of scrotum)
9
Q
Inguinal canal
A
Superficial inguinal ring is where the blood and nerve supply reach the testes. An inguinal hernia cuts off blood/nerve supply to the area.
10
Q
Semen fluids
A
Epididymis- storage of sperm in an acidic environment (5% of semen)
Seminal vesicle- adds fructose-rich fluids, prostaglandins, and ascorbic acid. (60% of semen)
Prostate- adds phosphatase and protease rich fluids (20%)
Bulbourethral/Cowper gland- mucus secretions (15%)
11
Q
During erection of the penis, what becomes rigid and pliable?
A
The corpus cavernosa becomes rigid
Spongy urethra remains pliable
12
Q
Stimulation of erection
A
Release of NO (parasympathetic)
13
Q
Ejaculation
A
Increased sympathetic input
14
Q
Spermatogenesis
A
Occurs between tight junctions near the basal membranes (not on the blood side). You can develop antibodies against sperm if the tight junctions are not tight enough in the Sertoli cells
15
Q
Testosterone secretion
A
Pulsatile- highest in morning
Peak 3 months gestation- formation of external genitalia
Peak 6 months old- male pattern thinking
16
Q
Sertoli cells secrete
A
Inhibin which inhibits FHS at the anterior pituitary
Androgen binding protein
17
Q
Sertoli cells have what receptors?
A
FSH
and aromatase allowing production of estrogen
18
Q
Estradiol in men
A
epiphyseal closure, prevention of osteoporosis, feedback of GnRH secretion
19
Q
Leydig cells secrete
A
testosterone which inhibits GnRH secretion at the hypothalamus and LH secretion at the anterior pituitary
20
Q
Leydig cells have what receptors?
A
LH receptors
21
Q
Pathologies of androgens in males during fetal life
A
Defect in 5alpha reductase- does not allow for DHT production, male genitalia does not fully develop
Androgen insensitivity- defect in androgen receptor, female appearance
22
Q
Pathologies of androgens in males during postnatal life
A
Hyposecretion before puberty - eunichs, female characteristics but tall
Hyposecretion after puberty- may not change characteristics
Early excess secretion- precocious puberty, lack of growth. Tx with GnRH analogues
23
Q
LH and FSH receptor abnormalities
A
McCune-Albright- precocious puberty in M and F
Activating mutations in LH- male-limited precocious puberty
Loss of function FSH receptor- infertility in M and F, amenorrhea in F
24
Q
Normal testosterone levels
A
300-1,100 n/dL
25
Exogenously administered androgens
can normalize systemic levels of testosterone by not normal seminiferous tubules. Can normalize the secondary characteristics but not spermatogenesis
26
Exogenous testosterone will inhibit
LH and FSH (impaired spermatogenesis)
27
Long term use of testosterone can cause
irreversible CV disease (cardiomyopathy, atherosclerosis)
28
Types of bone
Spongy bone- renewed at a rate of 20%/year
| Compact bone- renewed at a rate of 4%/year
29
Epiphyseal plate (growth plate)
Allows laying down of cartilage, which can become mineralized and allow the bone to grown in length. Mediated by GH/IGF-1 and thyroid hormone
30
Epiphyseal closure
Stimulation of estrogen receptors in cells of the epiphyseal growth plate leads to the conversion of cartilage into bone and terminates further longitudinal growth
31
Hydroxyapatite
Osteoid fluid within bone containing calcium and phosphate
32
Protein bone components
Type 1 collagen- vitamin C dependent. Measure through urinalysis
Non collagenous proteins- Vitamin K dependent
33
How much of plasma calcium in the active (ionized) form?
45%
34
What is the major site of homeostatic control of calcium
GI tract
35
What factors effect serum calcium?
Hypoalbuminemia leads to hypocalcemia
| Hyperproteinemia leads to hypercalcemia
36
PTH regulation of calcium
PTH is magnesium dependent and comes from the parathyroid gland
It increases calcium, decreases phosphate, and increases vit D production
37
Vitamin D (calcitriol) regulation of calcium
increases serum calcium and phosphate
38
Calcitonin regulation of calcium
decreases serum calcium
39
estrogens regulation of calcium
inhibit bone resorption, increase Vit D, increase calcitonin
40
where does the rate limiting step of the metabolism of vitamin D occur?
Kidney
41
How do restore plasma calcium (in hypocalcemia)
decrease phosphate, increase calcium abs
42
Resorption of bone is stimulated by
PTH
43
Building of bone is stimulated by
calcitonin
44
Med causes of osteoporosis
aluminum-containing antacids, anticonvulsants, chemotherapy/immunosuppressants, glucocorticoids, GnRH, heparin, levothyroxine, lithium, methotrexate, pioglitazone, SGLT2i, SSRIs
45
FRAX tool
age, gender, prior osteoporotic fracture, femoral neck BMD, low BMI, oral glucocorticoids >3 months, current smoking, alcohol intake, parental h/o hip fractures, secondary causes of OP, RA
46
BMD screening methods
Central DXA (GOLD standard)
-measures BMD at total hip, femoral neck, lumbar spine
Peripheral DXA- not preferred.
-measures BMD at distal radius, heel, finger
47
T scores
compare bone density to the average bone density of an average, healthy 20-30 yo adult
48
Normal T score
Above -1.0 SD
49
Osteopenia T score
-1.0 to -2.5 SD
50
Osteoporosis T score
Below -2.5 SD
51
Screening recommendations for osteoporosis
```
Women >65 yo
Postmenopausal women <65 with
-h/o low trauma fracture
-chronic glucocorticoid therapy
-Radiographic osteopenia
-Risk factors
```
52
Vertebral fracture assessment (VFA)
Most common osteoporotic fracutres
Lateral spine imaging with XR or VFA with DXA indicated for patietns with
-T score less than -1.0 SD AND
-women >70, men >80
-Historical height loss >4 cm (1.5 inches)
-Self reported prior vertebral fracture
-Glucocorticoids >5mg/day for >3 months
-Kyphosis
53
Osteoporosis diagnostic criteria
T score at or below -2.5 SD
Low trauma hip or spine fracture regardless of BMD
T score -1.0 to -2.5 SD WITH fragility fracture of proximal humerus, pelvis, or distal forearm OR high FRAX probability score
54
Nonpharm treatment of osteoporosis
increase vit D and calcium, exercise, smoking cessation, fall prevention, avoid excess alcohol
55
Calcium supplementation in adults >50
Recommend dietary intake of calcium 1200mg QD
| Supplemental intake 500-1000mg calcium daily
56
Vitamin D intake >50
Supplemental vitamin D 800-1000 units daily
| If insufficient/deficient- Vit D3 5,000 units QD for 8-12 weeks followed by maintenance therapy of 1-2,000 units QD
57
Insufficient vitamin D
20-29 ng/dL
58
Vitamin D deficient, serum
<20ng/dL
59
Pharmacologic options for osteoporosis
```
Biphosphonates
Calcitonin
Estrogen agonist/antagonist
Estrogen
PTH analogue
RANK ligand inhibitor
Sclerostin inhibitor
```
60
Estrogen agonist/antagonist MOA
induces osteoclast apoptosis, decreases RANKL-induced osteoclast differentiation, maintains osteoblast function
61
Estrogen receptor agonist/antagonist agents
Raloxifene
| Bazedoxifene
62
Raloxifene uses
Prevention and treatment of vertebral fractures in postmenopausal women
63
Raloxifene AE
thromboembolic events, hot flashes, leg cramps
64
BBW of raloxifene
Increased risk of VTE, CV disease
65
Bazedoxifene + conjugated estrogen uses
prevention of osteoporosis in postmenopausal women <75 yo
66
Estrogen MOA for osteoporosis
induces osteoclast apoptosis, decreases RANKL induced osteoclast differentiation, maintains osteoblast function
67
Estrogen AE
Nausea, HA, breast tenderness, heavy bleeding
68
Estrogen uses
prevention of osteoporosis in postmenopausal women
69
Estrogen contraindications
H/O or current VTE, active or h/o thromboembolic disease, thrombophilic disorder, active or h/o breast cancer, hepatic impairment
70
Estrogen BBW
endometrial cancer, CV disease, dementia, risk vs benefit
71
Calcitonin MOA
directly inhibits osteoclast mediated resorption
72
Calcitonin uses
treatment of hypercalcemia. Limited efficacy in treating fractures
73
Calcitonin AE
N, flushing, runny nose, hypocalcemia
74
Calcitonin warnings
Long term use associated with increased risk of cancer
75
Biphosphonates MOA
inhibits osteoclast function, induce osteoclast apoptosis
76
Biphosphonates agents
Alendronate, risedronate, ibandronate, zoledronic acid
77
Alendronate uses
prevention/tx of osteoporosis in men/women.
| Vertebral, non-vertebral and hip
78
Risedronate uses
Prevention of osteoporosis in women
Prevention and treatment in W and M
Vertebral, non-vertebral, hip
79
Ibandronate uses
Prevention/tx of osteoporosis in women
| Vertebral
80
Zoledronic acid uses
Prevention of osteoporosis in women
Treatment in men and women
Vertebral, non-vertebral, hip
81
Admin of biphosphonates
Stand or sit upright for 30-60 minutes after taking.
Zoledronic acid- IV only
Ibandronate- PO and IV
82
AE of biphosphonates
Osteonecrosis of the jaw, atypical femur fractures (chronic therapy, more common in Asian women)
PO-dysphagia, esophagitis, ulcers
IV- flu-like symptoms
83
Contraindications of biphosphonates
Hypocalcemia
| PO- esophageal abnormalities, inability to sit upright for 30 min
84
Parathyroid hormone 1-34 analog MOA
stimulates osteoblast function, increases calcium absorption, increases renal calcium and phosphate reabsorption
85
Parathyroid hormone 1-34 analog agents
Abaloparatide, Teriparatide
86
Abaloparatide uses
Tx or vertebral and non-vertebral fractures in postmenopausal women
87
Teriparatide uses
Treatment of vertebral and non-vertebral fractures in men and postmenopausal women
88
Parathyroid hormon 1-34 analog AE
hypercalcemia, orthostatic hypotension, muscle cramps, nausea, urolithiasis
Cumulative lifetime duration should not exceed 2 years
89
Parathyroid hormone 1-34 analog BBW
Potential risk of osteosarcoma. Avoid in patients with Pagets disease, h/o irradiation, open epiphyses, and elevated skeletal ALP
90
RANK ligand inhibitor MOA
monoclonal antibody against RANKL, inhibits osteoclast development and function
91
RANK ligand inhibitor agent
Denosumab
92
Denosumab uses
Tx of vertebral, non-vertebral, and hip fractures in men and postmenopausal women
93
What osteoporosis agent is preferred in renal insufficiency?
Denosumab
94
Denosumab AE
atypical femur fractures, dermatologic reactions, cellulitis, osteonecrosis of the jaw
95
Sclerostin inhibitor MOA
monoclonal antibody against sclerostin
96
Sclerostin inhibitor agent
Romosozumab
97
Romosozumab uses
treatment of vertebral, non-vertebral, and hip fractures in very high risk post menopausal women.
Treatment limited to 12 months
98
Romosozumab AE
arthralgia, hypocalcemia, atypical femur fractures, osteonecrosis of the jaw
99
Romosozumab BBW
potential risk of MI, stroke, CV death
100
When should you treat osteoporosis?
T score -1.0 to -2.5 with h/o fragility fracture
| T score 3% or FRAX MOF >20%
101
High risk osteoporosis (no previous fractures) treatment
Start with alendronate, risedronate, or zoledronic acid
102
Very high risk osteoporosis (prior fractures) treatment
start with abaloparatide, romosozumab, teriparatide, zolendronic acid
103
Therapeutic monitoring for pts on Rx therapy for osteoporosis
BMD testing q 1-2 years.
104
Treatment goals of osteoporosis
Stable OR increasing BMD at spine or hip
| No further fractures
105
Candidates for gender-affirming therapy (adults) WPATH criteria
Persistent, thorough documentation of gender dysphoria
Capacity of informed consent
Reasonable control of other significant health issues
106
WPATH criteria for puberty suppression
Adolescent demonstrates long-lasting and intense pattern of gender nonconformity of dysphoria
Gender dysphoria emerged or worsened at onset of puberty
Any co-existing conditions are stable
Informed consent is given and parents agree
107
Irreversible effects of feminization
Chest growth
108
Reversible effects of feminization
skin softening/decreased oiliness
Thinned/slowed terminal hair growth
Decreased muscle mass/strength
109
Variable effects of feminization
fat redistribution, decreased spontaneous arousals, decreased libido, ED, decreased testicular volume and sperm
110
Which estrogens are recommended for feminization?
Estradiol oral, SL, TD, IM
111
Androgen blockers
suppress/minimizes male secondary characteristics. Irreversible
Spironolactone, finasteride, dutasteride
112
Lab monitoring for feminization: BUN/SCr/K
Baseline, 3 mo, 6 mo, 12 mo, yearly, PRN if on spironolactone
113
Lab monitoring for feminization: Estradiol level
3 mo, 6 mo, PRN
114
Lab monitoring for feminization: total testosterone
3 mo, 6 mo, 12 mo, PRN
115
Lab monitoring for feminization: Sex hormone binding globulin
3 mo, 6mo, 12mo if pt is complex
116
Lab monitoring for feminization: albumin
3mo, 6mo, 12mo if checking SHBG
117
Lab monitoring for feminization: prolactin
if clinically indicated
118
General approach for feminizing hormones
increase both estrogen and antiandrogen until estrogen is in female physiologic range, then focus on androgen blockade
119
Goal hormone levels for feminization
Serum testosterone <50
| Peak estradiol 100-200 ng/dL
120
Estrogenic therapy considerations
Tobacco use increases risk of CV events
Loss of erectile function
Low libido
Pituitary adenoma
121
Why is blockade of feminizing hormones not recommended in masculinization?
Risk high for sexual side effects, CV disease, insulin resistance, and decreased bone mineral density
122
Irreversible effects of masculinization
Scalp hair loss, deepened voice, facial/body hair, clitoral enlargement
123
Reversible effects of masculinization
Skin oiliness/acne, increased muscle mass/strength, vaginal atrophy
124
Variable effects of masculinization
Fat redistribution
125
Which testosterones are recommended for masculinization?
testosterone cypionate and enanthate IM/SQ
| Testosterone 1%, 1.62%, 2% gel, patch, cream
126
Masculinizing therapy monitoring: estradiol
PRN
127
Masculinizing therapy monitoring: total testosterone
3 mo, 6 mo, 12 mo, PRN
128
Masculinizing therapy monitoring: sex hormone binding globulin
3 mo, 6mo, 12mo, PRN if pr is complex
129
Masculinizing therapy monitoring: albumin
3mo, 6mo, 12mo, PRN if checking SHBG
130
Masculinizing therapy monitoring: hematocrit and hemoglobin
Baseline, 3mo, 6mo, 12mo, yearly, PRN
131
What is considered clinical response in masculinization?
amenorrhea by 6 months
132
Masculinization recommended bioavailability of testosterone
>72 ng/dL
133
Testosterone therapy considerations
Erythrocytosis and polycythemia
Hair loss
Mental health
Cardiometabolic effects
134
GnRH analogs
Used for pubertal suppression in central precocious puberty.
REVERSIBLE
Ideally initiate in early puberty, but not prior to Tanner 2-3
135
ADR of GnRH analogs
injection site abscess and redness, withdrawal bleeding, hot flashes, emotional lability, HTN, weight gain, possible effects on growth
136
GnRH analog agents
Histrelin- implanted yearly
| Leuprolide
137
Annual monitoring with GnRH analogs
Everyone- LH, FSH, metabolic (renal, liver, lipids, glucose, A1C)
With testes- testosterone
With ovaries- estradiol
138
Gender affirming hormones in adolescents
Age >16, but individualized, may be ADDED TO GnRH analogs
