when should the diagnosis of primary amenorrhea be made and a diagnostic workup started? -
Answers When there has been no adrenarche or thelarche by age 13.
● When there has been no menses by age 15.
● When adrenarche or thelarche started on time, but menses have not started within 5 years of that
event.
The differential diagnosis includes anatomical, genetic, hormonal, enzymatic, and psychologic causes.
- Answers ● Anatomical - imperforate hymen or a transverse vaginal septum may mask onset of
menses.
● Uterus, no breasts - a lack of ovarian estrogen production due to chromosomal abnormalities
(Turner syndrome); ovarian enzyme deficiency; ovarian damage (radiation, chemotherapy); pituitary
or hypothalamic dysfunction (congenital hypogonadotropic hypogonadism)
● Breasts, no uterus - congenital absence of a uterus (complete uterine Mullerian agenesis) is found in
10% of cases of primary amenorrhea and is associated with other urogenital malformations, especially
in the urinary tract.
The menstrual cycle is often irregular early in puberty. The average for this time is 21-45 days with up
to 7 bleeding days, much longer periods without bleeding may occur. ACOG recommends evaluation
for menstrual abnormalities if any of the following occur: - Answers Menstrual periods that
● have not started within 3 years of thelarche
● have not started by 14 years of age with signs of hirsutism
● have not started by 14 years of age with a history of examination suggestive of excessive exercise or
eating disorder
● have not started by 15 years of age
● occur more frequently than every 21 days or less frequently than every 45 days
● occur 90 days apart even for one cycle
● last more than 7 days
● require frequent pad or tampon changes (soaking more than on every 1-2 hours)
● are heavy and are associated with a history of excessive bruising or bleeding or a family history of a
bleeding disorder
Actions Within the Reproductive Cycle - Answers Ovarian cycle
Follicular phase
Luteal phase:
Uterine (Endometrial) cycle:
Proliferative phase:
Secretory phase
Ovarian cycle - Answers - Development of a dominant follicle that results in ovulation and corpus
luteum formation.
Follicular phase: - Answers pulsatile GnRH is released by the hypothalamus and results in pulses of
FSH and LH from the anterior pituitary. The pulsatile stimulus recruits a number of follicles to begin
developing, which increases estrogen levels. One follicle becomes the dominant follicle producing the
most estrogen and the rest of the follicles stimulated in that cycle undergo atresia. Estrogen level
reaches peak, about 24 hours before ovulation. LH levels surge, and ovulation occurs 24-36 hours
later.
Luteal phase: - Answers ovulation indicates transition to luteal phase. A shift from estrogen
dominance to progesterone dominance occurs. Following the rupture of the follicle, the corpus
luteum develops and produces large amounts of progesterone. Progesterone suppresses further
follicular growth and causes secretory changes in the endometrium. Length of luteal phase tends to
be more constant than follicular phase, approximately 14 days. Progesterone causes elevation of
basal body temperature. If pregnancy does not occur, corpus luteum rapidly deteriorates
approximately 9-11 days after ovulation. A sharp decline in serum progesterone and estrogen levels
occur, triggering menstruation.
Uterine (Endometrial) cycle: - Answers Endometrium responds to cyclic changes in ovarian steroids by
preparing for implantation and fertilization. If pregnancy does not occur, the endometrium sloughs,
resulting in menstruation.
Uterine cycle is further divided into Proliferative and Secretory Phases.
, Proliferative phase: - Answers Corresponds to follicular phase of ovarian cycle; Estrogen stimulates
endometrium to thicken and form progesterone receptors to increase blood flow to endometrium.
Secretory phase - Answers -: Corresponds to luteal phase of ovarian cycle; Progesterone causes the
endometrium to differentiate and secrete proteins that are important in supporting implantation of
an early embryo if fertilization of the egg occurs.
identification of different types of breast masses - Answers fibroadenoma,
breast cyst;
Phyllodes Tumor;
Fibrocystic Breasts;
Nipple Discharge Galactorrhea;
Intraductal Papilloma:
Fibroadenoma - Answers : solid, noncancerous breast tumors that occur most often in adolescent girls
and women under the age of 30; usually firm, soft mobile lesions. Fibroadenomas are the most
common benign breast neoplasms. Evaluation includes observation through an entire menstrual cycle
to confirm persistence. In young women ultrasound is the preferred imaging.
Breast Cysts: - Answers common fluid-filled lesions in the terminal duct or lobule of the breast that
forms because of obstruction, involution, or aging of ducts within the breasts. May be palpable or
nonpalpable, simple or complex. Often fluctuate with the menstrual cycle; more common in the luteal
phase. Peak incidence is in women age 35 to 50 years of age. Postmenopausal women on hormone
therapy may have palpable cysts. Cysts that persist and grow in size require further evaluation. Cysts
that have thick walls and are hyperechoic on ultrasound have a 10 fold increase in risk of breast
cancer.
Fibrocystic Breasts - Answers More than 1/2 of all reproductive age women experience clinically
apparent changes often described as nodularity or glandular changes. Symptoms are typically bilateral
and increase prior to the menstrual cycles. Fibrocystic breasts are the most common of all benign
breast conditions. Cyclical bilateral breast pain is the classic symptom. Clinical signs include increased
breast engorgement and density, excessive breast nodularity, fluctuation in the size of cystic areas,
increased tenderness, and infrequently spontaneous nipple discharge.
Phyllodes Tumor - Answers a mixture of stroma and glandular tissue and is sometimes mistaken for a
fibroadenoma on exam. They account for less than 1% of breast masses. Occur in women 30 to 50
years of age. Excisional biopsy is necessary to eliminate the risk of a malignant tumor and to prevent
recurrence.
Nipple Discharge - Galactorrhea: - Answers spontaneous milky nipple discharge unrelated to
pregnancy or nursing, or occurring more than one year after weaning an infant. Hyperprolactinemia is
the main cause (related to medications, pituitary or hypothalamic disorder, renal disease, or
breast/nipple stimulation). Often associated with menstrual abnormality. An underlying malignancy is
more likely when the discharge is spontaneous, arises from a single duct, is blood stained, and is
unilateral and persistent. Underlying malignancy is present in 32% of women over the age of 60 and in
only 3% of women under 40 when nipple discharge is the only presenting symptom, age is important.
Intraductal Papilloma: - Answers most commonly diagnosed in perimenopausal women. Are broad
based or pedunculated polypoid epithelial lesions that may obstruct and distend the involved duct.
Clinical presentation includes an intermittent but spontaneous discharge from one nipple involving
one or two ducts. The discharge can be watery, serous, or bloody, and of variable volume. 75% are
located under the areola, are small and soft, and are difficult to palpate. Management includes careful
surveillance at 3 -4 month intervals and excision should be considered to rule out malignancy.
factors which impact drug metabolism - Answers The cytochrome P450 enzyme group is the main
driver of drug metabolism in an extensive list of pharmacotherapeutics. Sex hormones, drug
interactions (inhibitors and inducers) and social factors (drinking caffeine-containing beverages and
smoking) affect P450 enzymes.
NEED TO KNOW: Women express higher levels of CYP3A, the P450 subfamily that metabolizes drugs
such as cyclosporine, diazepam, imipramine, midazolam, nifedipine, quinidine, sex hormones,
tamoxifen, verapamil, and warfarin.
Drug metabolism - Answers NEED TO KNOW: Women express higher levels of CYP3A, the P450
subfamily that metabolizes drugs such as cyclosporine, diazepam, imipramine, midazolam, nifedipine,
quinidine, sex hormones, tamoxifen, verapamil, and warfarin.
breast cancer screening guidelines