Puberty and Disorders of Development and Menstrual Disorders Flashcards
1
Q
How does the menstrual cycle occur?
A
- GnRH from the hypothalamus stimulates the follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary, which stimulates estrogen and progesterone from the ovarian follicle
2
Q
Where is the pituitary gland located?
A
- Below the hypothalamus at the base of the brain within a bony cavity and is separated from the cranial cavity by a condensation of dura matter covering the sella turcica
3
Q
What are the two divisions of the pituitary? What does each produce?
A
- Anterior lobe: FSH, LH, TSH, prolactin, growth hormone, and ACTH
- Posterior lobe: Vasopressin and Oxytocin
4
Q
What are the phases of the normal ovarian cycle?
A
- Follicular phase: begins with the onset of menstruation and culminates in the preovulatory surge of LH
- Luteal phase: begins with the onset of the preovulatory LH surge and ends with the first day of menses
5
Q
What do decreasing levels of estradiol and progesterone from the regressing corpus luteum of the preceding cycle do?
A
- Initiate an increase in FSH by a negative feedback mechanism, which stimulates follicular growth and estradiol secretion
6
Q
What is a major characteristic of follicular growth and estradiol secretion?
A
- Is explained by the 2 gonadotropin (LH and FSH)
- 2 cell theory of ovarian follicular development
7
Q
What is the 2 cell theory of ovarian follicular development and estrogen production?
A
- Separate ovarian functions in the ovarian follicle
- LH stimulates the theca cells to produce androgens
- FSH stimulates the granulosa cells to convert these androgens into estrogen
8
Q
What happens during the luteal phase?
A
- LH and FSH are significantly suppressed at the start of the phase through the negative feedback effect of the elevated circulating estradiol and progesterone
9
Q
What happens if conception does not occur during the luteal phase?
A
- Progesterone and estradiol levels decline near the end of the luteal phase as a result of corpus luteal regression
- Then FSH will rise which initiates new follicular growth for the next cycle
10
Q
What are the 5 peptides that affect the reproductive cycle that are isolated from the hypothalamus?
A
- GnRH
- TRH
- SRIF or somatostatin
- CRF
- PIF
- All exert specific effects on the hormonal secretion of the anterior pituitary gland
11
Q
What is GnRH responsible for?
A
- Synthesis and release of LH and FSH
- Reaches the anterior pituitary and stimulates the synthesis and release of FSH and LH into the circulation
12
Q
What does estradiol do in regards to GnRH and LH?
A
- Enhance the hypothalamic release of GnRH and induce the midcycle LH surge
13
Q
What do gonadotropins do on GnRH release?
A
- Inhibitory effect
14
Q
When do estradiol levels begin to rise?
A
- Approximately 1 week before ovulation, they begin to rise
- Rise to a maximum 5 to 7 days after ovulation and returns to baseline before menstruation
15
Q
When are estrogen levels at a maximum?
A
- 1 day before the midcycle LH peak
16
Q
What happens with progestin during follicular development?
A
- Ovary secretes only a very small amount of progesterone
- Prior to ovulation the unruptured luteinizing graafian follicle begins to produce increasing amounts of progesterone
17
Q
Where does a bulk of progesterone come from during follicular development?
A
- The peripheral conversion of the adrenal pregnenolone and pregnenolone sulfate
18
Q
When does secretion of progesterone reach a maximum?
A
- Reaches a maximum 5-7 days after ovulation and returns to baseline before menstruation
19
Q
What happens to primordial follicles during follicular development?
A
- Undergoes sequential development, differentiation and maturation until a mature graafian follicle is produced
- Follicle then ruptures and releases an ovum
- Subsequent luteinization of the ruptured follicle produces the corpus luteum
20
Q
What happens about 8 to 10 weeks of fetal development?
A
- Oocytes become surrounded by precursor granulosa cells
- This complex is called the primordial follicle
21
Q
What is the cumulus oophorus?
A
- The innermost 3 to 4 layers of multiplying granulosa cells become cuboidal and adherent to the ovum
22
Q
How does the antrum and corona radiata form among the granulosa cells?
A
- Antrum enlarges and centrally located primary oocyte migrates to the wall of the follicle
- Innermost layer of the granulosa cells of the cumulus become elongated and form the corona radiata
- Corona radiata is release with the ootyce at ovulation
23
Q
How does ovulation start?
A
- Preovulatory LH surge initiates a sequence of biochemical and structural changes that result in ovulation
- Cells on the follicular wall surface degenerate and a stigma forms, follicular basement membrane bulges through the stigma
- When this ruptures, the oocyte is expelled into the peritoneal cavity
24
Q
What makes of the corpus luteum?
A
- Luteinized granulosa cells, theca cells, capillaries, and connective tissue
25
What does the corpus luteum do?
- Produced copious amounts of progesterone and some estradiol
- If pregnancy doesn't occur, menses does causing the corpus luteum to be replaced by avascular scar tissue called corpus albicans
26
What is the normal life span of the corpus luteum?
- 9 to 10 days
27
What is the endometrium responsive to?
- Circulating progestins, androgens, and estrogens
28
What are the two zones of the endometrium?
1. Outer portion or functionalis
| 2. Inner portion or basalis
29
What does the functionalis zone of the endometrium do?
- Undergoes cyclic changes in morphology during the menstrual cycle and is sloughed off at menstruation
- Contains spiral arteries
30
What does the basalis zone of the endometrium do?
- Remains relatively unchanged during each cycle and after menstruation provides stem cells for the renewal of the functionalis
- Contains basal arteries
31
What are the three stages of histopathology of the endometirum?
1. Menstrual phase
2. Proliferative or estrogenic phase
3. Secretory or progestional phase
32
What occurs during the menstrual phase?
- First day of menstruation is known as day 1
- Disruption and disintegration of the endothelial glands and stroma, leukocyte infiltration, and red blood cell extravasation
- Sloughing of the functionalis layer and compression of the basalis layer
33
What occurs during the proliferative phase?
- Endometrial growth secondary to estrogenic stimulation
| - Increase in length of spiral arteries and numerous mitoses can be seen in these tissues
34
What occurs during the secretory phase?
- Following ovulation, progesterone secretion by the corpus luteum stimulates the glandular cells to secrete mucus, glycogen and other substances
- Glands become tortuous and lumens are dilated and filled with these substances
- Stroma become edematous
- Spiral arteries extend into superficial layer of the endometrium and become convoluted
35
What happens if conception does not happen by day 23?
- Corpus luteum begins to regress, secretion of progesterone and estradiol decline, and endometrium undergoes involution
36
What happens the day before menstruation during the secretory phase?
- Marked constriction of the spiral arteries occurs resulting in ischemia of the endometrium, leukocyte infiltration and RBC extravasation
37
What is important in regulating menstruation?
- Intact coagulation pathway
38
How does coagulation affect menstruation?
- Menstruation disrupts blood vessels, but with normal hemostasis, they are repaired
- Restoration of the vessels requires successful interaction of platelets and clotting factors
- Anticoagulants impair the coagulation system and are associated with heavy bleeding
39
When does menarche occur?
- 12.43 is median age
- Occurs within 2-3 years after thelarche at Tanner stage IV, rare before tanner stage III
- By age 15, 98% of females have had menarche
40
What is primary amenorrhea?
- No menstruation by 13 without secondary sexual development OR by the age of 15 with secondary sexual characteristics
41
What is the average length of the first cycle and how many days do they bleed?
- Length is 34 days
| - Bleed for 2-7 days
42
What is the mean blood loss per menstrual period?
- 30cc
| - Most report changing a pad 3 to 6 times a day
43
What is blood loss of greater than 80cc associated with?
- Anemia
| - Changing a pad every 1-2 hours is considered excessive especially if bleeding is lasting >7 days
44
What is the usual age of puberty?
- 10-16 years old
45
What is the onset of puberty determined by?
- Genetic factors including race
- Geographic location (metro areas and near sea level begin puberty early)
- Obese children have earlier puberty
- Malnourished, chronically ill with weight loss will have later onset
46
What mean weight is essential to start menarche?
- 106 lbs
47
When do females have the peak number of oocytes?
- 6-7 million by mid-gestation (16-20 weeks)
48
What happens during ages 4-10?
- Hypothalamic-pituitary-ovary axis is suppressed
49
What 2 mechanisms do low levels of gonadotropins and sex steroids affect?
- Gonadostat sensitivity to the negative feedback of low circulating estradiol
- Intrinsic central nervous system inhibition of the hypothalamic GnRH secretion
50
What happens during ages 8-11?
- Is an increase in serum concentration of DHEA, DHEA-S, and androstenedione
51
What are the initial endocrine changes associated with puberty?
- Adrenal androgen production and differentiation by the zona reticularis of the adrenal cortex
52
What happens a result to a rise in adrenal androgens?
- Growth of axillary and pubic hair
53
How does puberty start?
- Around 11, there is a gradual loss of sensitivity by the gonadostat to the negative feedback of sex steroids. In combo with the intrinsic loss of central nervous system inhibition of hypothalamic GnRH release
54
What does an increase in GnRH promote?
- Ovarian follicular maturation and sex steroid production, which leads to the development of secondary characteristics
55
What happens by mid to late puberty?
- Positive feedback mechanism of estradiol on LH release from the anterior pituitary gland is complete and ovulatory cycles are established
56
What is thelarche? What is required?
- First physical sign of puberty
- Unilateral development in first 6 months is not uncommon
- Requires estrogen
57
What is pubarche and adrenarche? What is required?
- Pubic hair and axillary hair development
| - Requires androgens
58
When does maximal growth or peak height velocity occur?
- Occurs 2 years earlier in girls
| - Occurs about 1 year before onset on menses
59
What is required for menarche?
- Pulsatile GnRH from the hypothalamus, FSH and LH from the pituitary, estrogen and progesterone from the ovaries, normal outflow tract
60
What happens during Tanner stage 1 for breast development?
- Preadolescent
| - Elevation of papilla only
61
What happens during Tanner stage 2 for breast development?
- Breast bud stage
| - Elevation of breast and papilla as a small mound with enlargement of the areolar region
62
What happens during Tanner stage 3 for breast development?
- Further enlargement of breast and areola without separation of their contours
63
What happens during Tanner stage 4 for breast development?
- Projection of areola and papilla to form a secondary mound above the level of the breast
64
What happens during Tanner stage 5 for breast development?
- Mature stage
| - Projection of papilla only, resulting from recession of the areola to the general contour of the breast
65
What happens during Tanner stage 1 for pubic hair devleopment?
- Preadolescent
| - Absence of pubic hair
66
What happens during Tanner stage 2 for pubic hair development?
- Sparse hair along the labia
| - Hair downy with slight pigment
67
What happens during Tanner stage 3 for pubic hair development?
- Hair spreads sparsely over the junction of the pubes
| - Hair is darker and coarser
68
What happens during Tanner stage 4 for pubic hair development?
- Adult type hair
| - There is no spread to medial thigh
69
What happens during Tanner stage 5 for pubic hair development?
- Adult type hair with spread to the medial thighs assuming an inverted triangle pattern
70
What is precocious puberty?
- Starting puberty two standard deviations before expected age
- 8 years old for girls
- 9 years old for boys
71
What is needed to be done in precocious puberty?
- Thorough evaluation to eliminate a serious disease and to arrest potential osseous maturation that can affect normal growth patterns
72
What are the two types of precocious puberty?
1. Heterosexual precocious puberty
| 2. Isosexual precocious puberty
73
What is heterosexual precocious puberty?
- Development of secondary sexual characteristics opposite of those anticipated
- Think about: Virulizing neoplasms (sertoli leydig tumor), congenital adrenal hyperplasia, or exposure to exogenous androgens
74
What is isosexual precocious puberty?
- Premature sexual maturation that is appropriate for the phenotype of the affected individual
- Constitutional and organic brain disease (tumors, trauma, infectious process)
75
What is the most common cause of congenital adrenal hyperplasia (CAD)?
- Defect of the adrenal cortex enzyme 21-hydroxylase leading to excessive androgen production
76
What is classical CAD?
- Most severe forms cause cause birth of female with ambiguous genitalia
- If untreated progressive virilization and short adult status will result
77
What is unclassical CAD?
- Late onset adrenal hyperplasia can cause premature pubarche and an adult disorder resembling PCOS
78
How does true isosexual precocity arise?
- Premature activation of the normal process of pubertal development involving the HPO axis
79
How does pseudoisosexual precocity arise?
- Exposure to estrogens independent of HPO axis like estrogen producing tumors
80
How is isosexual precocious puberty diagnosed?
- Administration of exogenous GnRH and see a resultant rise of LH levels consistent with older girls who are undergoing normal puberty
81
What are some CNS disorders that could cause isosexual precocious puberty?
- Tumors
- Obstructive lesions (hydrocephalus)
- Granulomatous disease (sarcoidosis, TB)
- Infective processes (meningitis, encephalitis, or brain abscess)
- Neurofibromas
- Head trauma
82
How could a CNS disorder cause precocious puberty?
- May interfere with normal inhibition of hypothalamic GnRH release
- May often exhibit neural deficits before puberty development
83
What is the treatment for isosexual precocious puberty?
- GnRH agonist which suppresses pituitary release of LH and FSH, resulting in the decline of gonadotropins to prepubertal levels and arrest of gonadal sex steroid secretion
84
What can occur of isosexual precocious puberty is not treated?
- Half of girls will not reach 5 feet
85
What are two syndromes that may cause pseduoisosexual precocious puberty?
- McCune-Albright syndrome
| - Peutz-Jehgars syndrome
86
How could McCune-Albright syndrome cause pseudoisosexual precocious puberty?
- Somatic mutation during embryogenesis which causes them to function independent of their normal stimulation hormones
- Will have multiple cystic bone defects, cafe au lait spots
- Adrenal hypercortisolism
87
How could Peutz-Jehgars syndrome cause pseudoisosexual precocious puberty?
- Associated with a sex cord tumor that secretes estrogen
| - GI polyposis and mucocutaneous pigmentation
88
When is puberty considered delayed?
- Secondary sexual characteristics have not appeared by the age of 13
- If thelarche has not occurred by 14
- No menarche by age 15-16
- When menses has not begun 5 years after the onset of thelarche
89
What is a cause of hypergonadotropic hypogonadism/
- Gonadal dysgenesis (Turner)
90
What are some causes of hypogonadotropic hypogonadism?
- Constitutional (physiologic) delay
- Kallmann syndrome
- Anorexia/extreme exercise
- Pituitary tumors/disorders
- Hyperprolactinemia
- Drug use
91
What are some anatomic causes of delayed puberty?
- Mullerian agenesis
- Imperforate hymen
- Transverse vaginal septum
92
What is amenorrhea?
- Absence of menses
93
What is primary amenorrhea?
- No spontaneous uterine bleeding by age of 13 without secondary sexual characteristics
- No menstruation by 15 years old with secondary sexual development
94
What is secondary amenorrhea?
- Patient with prior menses has absent menses for 6 months or more
95
What are the diagnostic findings of primary amenorrhea with absence of secondary sexual characteristics?
- FSH, LH
96
What is Kallmann syndrome?
- Mutation of the KAL gene on the x chromosome that prevents the migration of the GnRH neurons into the hypothalamus
- Patients with often have anosmia or hyposmia (no or little smell)
97
What tests can be done to evaluate for primary amenorrhea with absence of secondary sexual characteristics?
- MRI of brain
- FSH
- Karyotype
- Progesterone
- Prolactin
98
What is the physical presentation of someone with Turner's syndrome?
- Webbing of the neck
- Broad flat chest like a shield with widely spaced nipples
- Short stature
- Rudimentary streaked ovaries
- Absent or incomplete development of puberty
- Coarctation of the aorta
99
What are the two categories of primary amenorrhea with breast development and mullerian anomalies?
1. Androgen insensitivity syndrome
| 2. Mullerian agenesis
100
What are some characteristics of androgen insensitivity syndrome (AIS)?
- Male levels of testosterone
- 46XY
- Defect in androgen receptor
- Testes are in abdominal wall and secrete normal amounts of anti mullerian hormones meaning no uterus
101
What does the external genitalia look like in AIS?
- External female genitalia with absent to sparse pubic hair
- Breast development with smaller than normal areola and nipples due to estrogen secretion in testes and conversion of androgens to estrogen in the liver
102
What is mullerian agenesis (MRKH syndrome)?
- Failure of mullerian ducts to fuse distally and to form the upper genital tract
- Absent uterus but may have a unilateral or bilateral rudimentary uterine tissue, tubes, and ovaries
- May have renal abnormalities
103
What are some characteristics of mullerian agenesis?
- Normal secondary development and external female genitalia
- Normal female range of testosterone
- Absent uterus and upper vagina
- Normal ovaries
- 46XX
104
What does history and physical reveal for secondary amenorrhea?
- Significant changes in weight
- Strenuous exercise
- Dietary habits
- Concomitant illes
- Abnormal facial hair
- Galactorrhea
- Dysparenuia
- Presence of hot flashes or night sweats
105
What labs are done for secondary amenorrhea?
- Urine hCG
- TSH
- Prolactin
- FSH
106
What will thyroid disease show in the labs?
- Normal prolactin
| - Abnormal TSH
107
What will be seen in hypothyroidism?
- Hypermenorrhea or oligomenorrhea
| - Treatment should restore menses
108
What is seen in abnormal prolactin levels?
- Normal TSH
| - Galactorrhea is the most common symptom of hyperprolactinemia
109
What is done for really high prolactin (≥100ng/ml)?
- Evaluate for prolactinemia with head MRI to check for empty sella syndrome or pituitary adenoma
110
What is done for high prolactin (<100ng/ml)?
- If MRI is negative, consider other causes
111
What is done for microadenomas found on MRI?
- Monitored with repeat prolactin measurements and imaging
- Typically slow growing and rarely malignant
- Treatment should focus on management of infertility, galactorrhea, and breast discomfort
- Consideration for dopamin agonist
112
What is done for macroadenomas found on MRI?
- May be treated with dopamine agonists
| - Transphenoidal resection or craniotomy
113
What are some causes of prolactin <100ng/ml?
- Ectopic production
- Breast feeding and stimulation
- Excessive exercise
- Severe head trauma
- Hypothyroidism
- Liver or renal failure
- Meds like OCPs, antipsychotics, antidepressants, antihypertensives, H2 blockers, opiates, cocaine
114
What is done if there is normal TSH and prolactin in secondary amenorrhea?
- Progesterone challenge test
115
What is a positive progesterone challenge test?
- Positive bleeding
| - Normogonadotropic hypogonadism (PCOS is most common)
116
What is a negative progesterone challenge test?
- No withdrawal bleeding
| - Indicates inadequate estrogenization or an outflow tract abnormality
117
What is done after a progesterone challenge test?
- Do an estrogen/progesterone challenge test
118
What does a negative estrogen/progesterone challenge test indicate?
- Outflow tract obstruction
119
What does a positive estrogen/progesterone challenge test indicate?
- Abnormality with the hypothalamic pituitary axis or ovaries
120
What is seen in a positive estrogen/progesterone challenge test?
- Elevated FSH and LH would indicate ovarian abnormality
| - Normal FSH and LH would indicate pituitary or hypothalamic abnormality
121
What is nonclassic congenital adrenal hyperplasia?
- Elevated 17-hydroxyprogesterone
- Does not present with genital abnormalities
- Associated with hirsutism, acne, and menstrual irregularities around puberty
122
What are some causes of normogonadotropic amenorrhea with hyperandrogenism following a positive PCT?
- Nonclassic congenital adrenal hyperplasia
- Cushing's syndrome
- Adrenal androgen secreting tumor
- PCOS
- Sertoli leydig cell tumor
123
What does PCOS cause?
- Leading cause of female anovulatory infertility
- 60-70% of patients have decreased insulin sensitivity causing to insulin hypersecretion
- Elevated insulin and androgen levels reduce the hepatic production of sex hormone binding globulins leading to increase circulating testosterone
124
How is the diagnosis for PCOS made?
- Oligomenorrhea or amenorrhea
- Biochemical or clinical signs of hyperandrogenism (LH to FSH 2:1)
- U/S revealing multiple small cysts beneath the cortex of the ovary
125
What are some features of PCOS?
- Anovulation
- Hyperandrogenism
- Hirsutism
- Acne
- Menstrual dysfunction
- Hyperinsulinemia
- LH hypersecretion
- Elevated testosterone
- Acyclic estrogen production
- Obesity
- Sleep disorders
- Acanthosis nigricans
- Lipid abnormalities
126
What are some treatment options for PCOS?
- Weight loss
- OCPs to suppress gonadotropins
- Clomiphene citrate which can induce ovulation
- Ovarian diathermy/laser treatment
- Spironolactone
- Insulin sensitizing agents
127
What are some causes of hypergonadotropic hypogonadism (FSH >20 IU and LH >40 IU) in secondary amenorrhea?
- Postmenopausal ovarian failure (ave age of menopause is 51)
- Premature ovarian failure (before 40)
- Ovarian injury from surgery
- Pelvic radiation
- Autoimmune and mumps
128
What are some causes of hypogonadotropic hypogonadism (FSH and LH <5) in secondary amenorrhea?
- Anorexia or bulimia
- Chronic illness
- Cranial radiation
- Excessive exercise
- Malnutrition and weight loss
- Sheehan's syndrome
129
What labs are done during evaluation of hyperandrogenism?
- 17-hydroxyprogesterone to exclude CAH
- 24 hour free cortisol to rule out Cushing's
- Prolactin and TSH for hyperprolactinemia and thyroid dysfunction
- Glucose and lipid levels
- Testosterone and DHEA-S
130
What does PALM stand for in AUB?
- Polyp
- Adenomyosis
- Leiomyoma
- Malignancy and hyperplasia
131
What does COEIN stand for in AUB?
- Coagulopathies (Von willebrand disease)
- Ovulatory dysfunction (PCOS)
- Endometrial causes (infection)
- Iatrogenic (IUD, IUS, exogenous hormones )
- Not yet classified (AVM)
132
What medical history is needed of AUB?
- Age of menarche and menopause
- Menstrual bleeding patterns
- Severity of bleeding
- Pain
- Medical conditions
- Surgical history
- Use of medications
- Symptoms and signs of possible hemostatic disorders
133
What laboratory tests are done for AUB?
- Pregnancy test
- CBC
- Targeted screening for bleeding disorders
- TSH
- Chlamydia trachomatis
134
What is the treatment for massive bleeding in AUB?
- Hospitalization and transfusions if hemodynamically unstable
- 25 mg IV conjugated estrogens then hormonal treatment
135
What is the treatment for moderate bleeding in AUB?
- Combination OCPs, Mirena
136
What is done if treatment is unresponsive in AUB?
- D&C, polypectomy, myomectomy, endometrial ablation, hysterectomy
