Menstrual Cycle

What timing or course details are emphasized for menstrual cycle phases?

Follicular phase and luteal phase. Proliferative phase and secretory phase. The follicular phase. The luteal phase. The first day of menstrual bleeding.

What hormonal or physiologic features are emphasized for follicular/proliferative phase?

FSH. Estrogen. It causes the uterine lining to proliferate/thicken.

What does FSH cause during the follicular phase?

Development of a primary follicle.

What timing or course details are emphasized for ovulation and luteal phase?

LH spikes in response to the estrogen surge, resulting in ovulation. The luteal phase. A corpus luteal cyst/corpus luteum.

What hormonal or physiologic features are emphasized for ovulation and luteal phase?

The LH surge. Progesterone. It maintains the uterine lining for a fertilized ovum. hCG.

What happens to the corpus luteum if fertilization does not occur?

It degenerates, and menstruation occurs.

What other key facts are emphasized for follicular development and estrogen production?

Primordial follicle -> primary follicle -> secondary follicle -> preovulatory follicle -> ovulation and luteinization/corpus luteum. Granulosa cells.

What anatomic features are emphasized for follicular development and estrogen production?

Pre-granulosa cells. Theca cells.

What enzymes and estrogen products are shown in the granulosa-cell estrogen pathway?

P450 aromatase. Estradiol (E2), estrone (E1), and estriol (E3). 17β-HSD1 and 17β-HSD2.

What enzyme label is shown between androstenedione and testosterone in the theca cell?

AKR1C3.

What hormonal or physiologic features are emphasized for cycle hormone and endometrial patterns?

Estrogen rises before ovulation, LH has the sharpest mid-cycle surge, FSH has a smaller mid-cycle rise, and progesterone rises mainly during the luteal phase. During the luteal/secretory phase after ovulation.

When does the endometrium thicken most prominently in the cycle diagram?

During the proliferative phase after menses and especially through the secretory phase after ovulation.

How does the PowerPoint define primary amenorrhea?

No menses by age 16 or 4 years after thelarche.

What three broad categories of causes are listed for primary amenorrhea?

Outflow tract abnormalities, end-organ disorders, and central disorders.

How does the PowerPoint define secondary amenorrhea?

No menses for more than 6 months or 3 cycles in a woman who previously had menstrual cycles.

What major categories of secondary amenorrhea are listed?

Pregnancy, anatomic abnormalities, ovarian failure, PCOS, hyperprolactinemia, and disruption of the hypothalamic-pituitary axis.

What is the most common cause of secondary amenorrhea?

Pregnancy.

What defines imperforate hymen?

Failure of the hymen to canalize during fetal development, leaving a solid membrane across the vaginal introitus that prevents menstrual egress. Accumulated menstrual blood behind the outflow obstruction.

What symptoms/signs are listed for an imperforate hymen?

Pelvic/abdominal pain, a bulging membrane inside the introitus with purple/red discoloration, and hematocolpos.

How is an imperforate hymen treated according to the PowerPoint?

Surgically with a cruciate incision; the hymen is sewn open.

What is a transverse vaginal septum?

Failure of the Müllerian-derived upper vagina to fuse with the urogenital-sinus-derived lower vagina, commonly at the mid vagina.

What symptoms/signs are listed for a transverse vaginal septum?

Cyclic pelvic pain and a bulging septum with hematocolpos.

How is a transverse vaginal septum treated?

Surgical resection of the septum.

What handwritten concept accompanies imperforate hymen/transverse vaginal septum?

The period cannot come out because of the outflow obstruction.

What is MRKH syndrome?

Mayer-Rokitansky-Kuster-Hauser syndrome.

What karyotype is associated with MRKH in the PowerPoint?

46,XX.

What anatomy is described in MRKH?

Missing uterus and upper vagina with normal ovaries and no patent vagina on physical exam.

What is vaginal atresia?

The Müllerian system is developed, but the distal vagina is composed of fibrous tissue.

How can a neovagina be created for vaginal atresia?

With vaginal dilators or reconstructive surgery.

What is testicular feminization syndrome also called?

Androgen insensitivity syndrome (AIS).

What karyotype is associated with AIS?

46,XY.

What is the receptor problem in AIS according to the slide?

Dysfunction or absence of the testosterone receptor.

What is the phenotype in AIS?

Phenotypical female.

How does androgen insensitivity syndrome typically present?

Lack of pubic and axillary hair. Testes are present and breast development is present.

What risks/issues are noted in AIS?

Risk for testicular cancer and psychosocial issues.

What type of hypogonadism is ovarian failure classified as in the PowerPoint?

Hypergonadotrophic hypogonadism.

What hormone pattern is listed for ovarian failure?

Low estradiol with elevated gonadotropins.

What is Savage syndrome?

Ovaries fail to respond to FSH/LH secondary to a receptor defect.

What karyotype is listed for Turner syndrome?

45,XO (monosomy X).

What happens to the ovaries in Turner syndrome according to the slide?

They undergo rapid atresia with no oocytes.

What enzyme defect is listed on the Turner syndrome slide?

Defect in 17-hydroxylase.

What breast-development finding is listed for Turner syndrome?

Absence of breast development.

What genetic features are emphasized for gonadal agenesis?

No female internal reproductive organs and no breast development. Phenotypically female. Testicular feminization syndrome secondary to absence of or defect in enzymes involved in testicular steroid production.

What genetic features are emphasized for Swyer syndrome?

46,XY. SOX9, WT1, and SF1. SRY gene mutation -> no functional testes -> no testosterone and no anti-Müllerian hormone (AMH).

What genital/uterine anatomy is described in Swyer syndrome?

Normal female genitalia with a uterus.

How does Swyer syndrome typically present?

Streak gonads. No/poor breast development. Lack of secondary sexual characteristics. Uterus and fallopian tubes.

What other key facts are emphasized for Swyer syndrome?

Tall stature. Low estrogen/testosterone with increased FSH and LH (hypergonadotropic hypogonadism); AMH is absent.

What is Swyer syndrome described as in the infographic?

46,XY gonadal dysgenesis in which a genetically male individual develops a female phenotype because of failure of testicular development.

What important malignancy risk is listed for Swyer syndrome?

High risk of gonadoblastoma (20%-30%) due to Y-chromosome material.

How is Swyer syndrome managed according to the PowerPoint?

Mandatory removal of gonads due to malignancy risk. Treat with estrogen first, then progesterone.

How is Turner syndrome defined in the infographic?

A chromosomal disorder seen only in females caused by complete or partial absence of one X chromosome, most commonly 45,X.

What Turner karyotypes are listed in the infographic?

45,X most commonly and mosaic 45,X/46,XX; structural abnormalities such as an isochromosome/ring X are also listed.

How does Turner syndrome typically present?

No Barr body. Delayed puberty, poor breast development, primary amenorrhea, and infertility due to streak gonads. Lymphedema of hands and feet, webbed neck, and low posterior hairline. Short stature, broad/shield chest with widely spaced nipples, cubitus valgus, and recurrent otitis media.

What epidemiologic facts are emphasized for Turner syndrome?

About 1 in 2,500 live female births. Most common sex chromosome abnormality in females.

What other key facts are emphasized for Turner syndrome?

Coarctation of the aorta, bicuspid aortic valve, and aortic root dilatation. Horseshoe kidney and duplex collecting system. Normal intelligence with specific learning difficulty in spatial and mathematical skills. Short female + webbed neck + primary amenorrhea = Turner syndrome. Short stature, webbing of neck, broad chest and widely spaced nipples, cubitus valgus, pigmented nevi, low posterior hairline, coarctation of aorta, streak ovaries/infertility/amenorrhea, and peripheral lymphedema at birth.

How is Turner syndrome evaluated or diagnosed?

Karyotype analysis. Cystic hygroma and hydrops.

What gonadotropin pattern is shown for Turner syndrome in the infographic?

Increased FSH and LH (hypergonadotropic hypogonadism).

What causes or etiologies are listed for causes of ovarian failure?

Idiopathic; Turner syndrome (45XO) or mosaic Turner (45X/46XX); trisomy X (47XXX or mosaic); Fragile X premutation; galactosemia; autoimmune polyglandular syndrome types 1 and 2; FSH receptor mutations; 17α-hydroxylase deficiency; aromatase deficiency; blepharophimosis-ptosis-epicanthus inversus syndrome; Bloom syndrome; ataxia telangiectasia; and Fanconi anemia. Autoimmune. Mumps oophoritis; tuberculosis, malaria, cytomegalovirus, varicella, and shigella. Bilateral oophorectomy, bilateral ovarian cystectomies, chemotherapy (primarily alkylating agents and anthracyclines), radiation (external beam or intracavitary), environmental toxins, and pelvic vessel embolization.

What broad disorders are included under primary amenorrhea central disorders?

Hypothalamic disorders and pituitary disorders.

What type of hypogonadism is associated with hypothalamic/pituitary failure?

Hypogonadotrophic hypogonadism.

Why will the pituitary not release FSH/LH in hypogonadotrophic hypogonadism according to the slide?

Because the hypothalamus is unable to produce GnRH.

What does GnRH stand for?

Gonadotropin-releasing hormone.

What is Kallmann syndrome according to the PowerPoint?

Congenital absence of GnRH.

What classic sensory finding is associated with Kallmann syndrome?

Anosmia.

What causes or etiologies are listed for central causes of primary amenorrhea?

Tumor mass effect, trauma, sarcoidosis, TB, radiation, and Hand-Schuller-Christian disease. Anorexia, extreme stress, hyperprolactinemia, hypothyroidism, rapid or severe weight loss, and delayed puberty.

How does the primary amenorrhea algorithm begin when secondary sexual characteristics are absent?

Are secondary sexual characteristics present? FSH and LH. Hypogonadotropic hypogonadism. Hypergonadotropic hypogonadism.

How does karyotype distinguish causes of hypergonadotropic primary amenorrhea in the algorithm?

Swyer syndrome. Premature ovarian failure. Turner syndrome.

How does the primary amenorrhea algorithm proceed when secondary sexual characteristics are present?

Is a uterus present? Outflow obstruction. Evaluate as for secondary amenorrhea.

How is primary amenorrhea diagnostic algorithm evaluated or diagnosed?

Karyotype analysis. Imperforate hymen or transverse vaginal septum. Karyotype analysis. Androgen insensitivity syndrome. Müllerian agenesis.

What causes or etiologies are listed for primary amenorrhea diagnostic algorithm?

Pregnancy, anatomic abnormalities, ovarian failure, PCOS, hyperprolactinemia, and disruption of the hypothalamic-pituitary axis. D&C, myomectomy, cesarean delivery, and endometritis.

What defines primary amenorrhea diagnostic algorithm?

Uterine synechiae or adhesions resulting from surgery or infection. Surgical or obstetric trauma.

What symptom may occur with cervical stenosis?

Dysmenorrhea.

What handwritten treatment note appears next to Asherman syndrome?

Dilation and curettage.

What causes or etiologies are listed for premature ovarian failure?

Ovarian torsion, surgery, infection, radiation, and chemotherapy. It is often idiopathic.

How does the PowerPoint define premature ovarian failure?

Menopause before age 40.

What is recommended if premature ovarian failure occurs before age 35?

Chromosomal analysis.

What handwritten genetic note appears with premature ovarian failure before age 35?

Fragile X chance.

What treatment is listed for premature ovarian failure?

Estrogen to decrease the risk of cardiovascular disease and osteoporosis.

What does PCOS stand for?

Polycystic ovarian syndrome.

What high-yield hormonal and syndrome features are emphasized for PCOS?

Stein-Leventhal syndrome. Elevated estrogen and androgen levels with an abnormal LH:FSH ratio. Hyperandrogenism + ovulatory dysfunction + metabolic disturbance.

What ovarian, fertility, and cycle-control features are emphasized for PCOS?

OCP or levonorgestrel IUD. Polycystic ovaries on ultrasound with multiple small peripheral follicles, enlarged ovarian stroma, and a "string of pearls" appearance. Anovulation, subfertility/infertility, and difficulty conceiving.

What diagnostic criteria are emphasized for PCOS?

2 of the 3 criteria. Oligo-anovulation; clinical or laboratory evidence of hyperandrogenism; polycystic ovaries on ultrasound.

What causes or etiologies are listed for PCOS?

Unknown. Unopposed estrogen increases endometrial cancer risk.

What LH:FSH ratio is written on the PCOS slide?

2-3:1.

What risks or complications are emphasized for PCOS?

Type 2 diabetes. Secondary to obesity/insulin resistance. Type 2 diabetes, metabolic syndrome, endometrial hyperplasia risk from unopposed estrogen, and possible dyslipidemia.

How is PCOS managed according to the PowerPoint?

Weight loss. Ovulation induction with clomiphene citrate (Clomid); metformin if insulin resistant.

What are the goals for a PCOS patient not trying to conceive?

Cycle control, reduction of endometrial cancer risk, and treatment of acne and hirsutism.

What ultrasound buzzword is written for PCOS?

"String of pearls" on ultrasound.

How does PCOS typically present?

Oligomenorrhea/amenorrhea, irregular cycles, chronic anovulation; it is a common presenting feature. Hirsutism, acne, and androgenic alopecia; clinical or biochemical hyperandrogenism is key. Insulin resistance, central obesity/weight gain, and acanthosis nigricans.

What common endocrine, medication, tumor, and physiologic causes of hyperprolactinemia are listed?

Primary hypothyroidism. Haldol, Reglan, phenothiazine, tricyclic antidepressants, MAO inhibitors, and opiates. Pituitary adenoma/prolactinoma. Pregnancy and breastfeeding.

What additional pituitary-relationship, neural, chest-wall, and CNS causes of hyperprolactinemia are listed?

Hypothyroidism, idiopathic hyperprolactinemia, drug-induced hyperprolactinemia, interruption of the normal hypothalamic-pituitary relationship, peripheral neural stimulation, and central nervous system disease. Pituitary stalk section. Chest wall stimulation, thoracotomy, mastectomy, thoracoplasty, burns, herpes zoster, bronchogenic tumors, bronchiectasis, chronic bronchitis, nipple stimulation, chronic nipple irritation, spinal cord lesion, tabes dorsalis, and syringomyelia. Encephalitis, craniopharyngioma, pineal tumors, hypothalamic tumors, and pseudotumor cerebri.

What hormone elevations are listed with primary hypothyroidism in hyperprolactinemia?

Elevated TSH and TRH (thyrotropin-releasing hormone).

How is a pituitary adenoma associated with hyperprolactinemia treated according to the slide?

Bromocriptine; it can shrink the tumor and can also be used for ovulation induction.

What visual symptom is listed with a pituitary adenoma?

Loss of peripheral vision.

What is empty sella syndrome?

The subarachnoid membrane herniates into the sella turcica.

What should patients with elevated prolactin undergo according to the PowerPoint?

Imaging to rule out prolactinoma.

What pituitary-tumor sizes are listed in the hyperprolactinemia image?

Macroadenomas >10 mm and microadenomas <10 mm.

What mnemonic is shown for pituitary adenoma symptoms?

HAMMER.

What does the PowerPoint mnemonic for pituitary adenoma HAMMER mnemonic summarize?

Headache. Amenorrhea, or galactorrhea in prolactinoma. Mass effect, including visual loss/bitemporal hemianopsia. Mood changes such as depression and anxiety. Excess hormone secretion, such as Cushing's or acromegaly. Reduced libido due to hormonal imbalance.

What causes or etiologies are listed for hypothalamic-pituitary axis disruption and Sheehan syndrome?

Kallmann syndrome, hypothalamic tumors such as craniopharyngioma, constitutional delay of puberty, severe hypothalamic dysfunction, anorexia nervosa, severe weight loss, severe stress, and exercise. Severe bleeding during or after childbirth reduces blood flow to the pituitary, causing pituitary infarction and panhypopituitarism.