Benefits of Transdermal Estrogen replacement vs oral
- Provides 17-beta-estradiol, which is structurally identical to ovarian 17-beta-estradiol.
- Avoids the first-pass effect (which is a/w inc production of clotting factors).
- Replacement by steady infusion rather than by bolus.
- Reduces the risk of VTE vs oral route
- May be associated with a reduced risk of GB (ie, cholecystitis, cholelithiasis, and cholecystectomy)
(UTD)
Define Delayed Puberty and precocious puberty
1. No breast development age 13 No menses age 15 2. Before age 8 - < 7 caucasian - < 6 black
Most common cause Delayed Puberty
Hyper/Hypo (43%) gonadal failure
Hypo/Hypo (31%)
What does breast development suggest re: eugonadism vs hypogonadism
No breasts = hypogonadal
breasts = preduced estrogen at some point, assess current estrogen status with progestin withdrawal test
Pt with Hyper/Hypo: next step
Karyotype
- usually abn like 45x with mosaicism or 46XY (Swyer)
Hypo/Hypo pt: next step
MRI to r/o pituitary tumor
If no Tumor DDX:
- functional
- Irreversible - hypothalamic tumor, Kallmans, IHH
Eugonadism and amenorrhea DDX
Outflow obstruction
Mullerian Aplasia
AIS - no pubes, no ut/vagina s/t AMH production
Ovulatory dysfcn (PCO, Hyperprolactinemia, Thyroid dysfcn)
CASE: 17 y/o primary amenorrhea unable to smell FMx infertility Tanner 5 breast, vagina present 1. Investigations? 2. If she had no breast development would it be different?
1.
- Determine current Estrogen status - Tanner 5 breast
Progestin withdrawal bleed (Provera 10 x 10) = neg
- FSH, E2, TSH, PRL
- Bone age
2.
Yes - hypogonadism present if no breasts so no need to assess E2 status
CASE: 17 y/o primary amenorrhea unable to smell FMx infertility and anosmia Tanner 5 breast, vagina present FSH 2, Provera challenge failed 1. Dx 2. Next Step 3. Likely Cause 4. Tx
- Hypo/Hypo
- MRI
- Kallman’s
- Sex steroid replacement: Estrogen until breast development adequate then add progestin (combined OCP)
- Calcium/Vit D
- Gonadotropins for fertility
- Genetic counselling
What is the most common mutation for idiopathic Hypo/Hypo?
FGFR1
CASE: 16 y/o primary amenorrhea no breasts, short Tanner 3 pubic hair Declines pelvic 1. Ix 2. If Hyper/Hypo next steps 3. Likely Dx 4. Management
- FSH, TSH, PRL
- Karyotype
- Turners (45X)
- Remove the gonads!
- risk of cardiac /renal abn
- risk of hypothyroidism
- NO donor IVF - cardiac risks
19 y/o primary amenorrhea cervical spine immobility and joint pain no pelvic pain breasts present Tanner 5 pubic hair No vagina 1. DDX 2. most likely and what else to look at?
1.
- transverse vaginal septum or imperforate hymen (usually have pain, younger)
- complete AIS (usually Tanner 1-2)
- Mullerian aplasia
2. mullerian aplasia, kidneys
Usual time between thelarche and menarche
2-2.5 yrs
Which of the following aspects of puberty are HPO axis independent: thelarche, adrenarche, growth spurt, menarche?
Adrenarche (s/t adrenal secretion androgen)
Tanner Staging:
Breast:
- nothing
- breast bud
- mound
- secondary aoreolar mound
- adult
Pubic Hair:
- nothing
- sparse long hairs
- growth sparsely spread
- adult hair over mons
- spread to thighs
How is precoscious puberty divided/classified?
- Central/Gonadotropin dependent
- idiopathic (MOST COMMON)
- CNS abnormality
- Chronic exposure to sex steroids (McCune- Albright Syndrome, CAH, tumor) which start as peripheral and then activate puberty - Peripheral/Gonadotropin independent
- isosexual (estrogen)
- contrasexual (androgens)
Causes of peripheral precocious puberty
Ovarian tumors Adrenal d/o McCune albright syndrome Primary hypothyroidism (rare) Exogenous estrogen (rare)
most common tumor causing precocious puberty
granulosa cell tumors (60%)
What is McCune Albright Syndrome
Recurrent follicular cysts
Polyostotic fibrous dysplasia
irregular cafe au lait spots
What is the one cause of peripheral precoscious puberty that has delayed bone age (vs advanced)?
Primary Hypothyroidism
What lab results suggest early puberty?
- LH>FSH
- GnRH agonist stim test pos (LH elevated)
- E2 elevated
- Bone age advanced > 2SD
Tx of central precosious puberty
GnRH agonist suppress FSH and LH, d/c when 11-12
No longterm issues
CASE:
5 y/o breasts Tanner 3, pubic hair Tanner 1
75%ile for height (previously 5th)
1. Ix?
- bone age
- FSH/LH ratio
- E2
- TSH
CASE:
5 y/o breasts Tanner 3, pubic hair Tanner 1
75%ile for height (previously 5th)
IX: Advanced bone age, FSH>LH (prepubertal), E2 elevated, TSH nml
1. Dx
2. next step
3. most likely Dx, what does this procude?
- Peripheral precocious puberty
- pelvic US
- granulosa cell tumor, inhibin
