Reproductive Physiology Flashcards
What occurs in the follicular phase of the menstrual cycle.
During the follicular phase, FSH and LH stimulate the development of several follicles, one of which develops as the dominant follicle into the Graafian follicle. An LH surge initiates ovulation.
What occurs in the luteal phase of the menstrual cycle.
As the oocyte reaches the fallopian tube, the ruptured follicle transforms into the corpus luteum, which produces progesterone. If no pregnancy occurs, the corpus luteum regresses and the progesterone level drops. This drop induces vasospasms in the uterine spiral arteries, ischemia, and sloughing off of the functional endometrial layer, which leads to menstrual bleeding (menstrual phase). During the proliferative phase, the endometrium is built up again in preparation for oocyte implantation during the secretory phase.
What is primary and secondary amenorrhoea.
Primary: absence of menarche at 15 years of age despite development of secondary sexual characteristics or absence of menses at 13 years of age in female individuals with no secondary characteristics
Secondary: the absence of menses for more than 3 months in individuals with previously regular cycles, or 6 months in individuals with previously irregular cycles
What happens in hypogonadotropic hypogonadism?
- Deficient release of GnRH (by the hypothalamus)
- Common congenital cause: Kallmann syndrome with anosmia
- Other causes: competitive sports, stress, eating disorders
- Prader Willi - choromsome 15
- CNS tumours: cranipharyngioma
- Low GnRH, normal/low LH/FSH, low estrogen
What happens in hypergonadotropic hypogonadism?
- GnRH is being produced but there is ovarian failure unable to produce estrogen and progesterone
- Main cause is turner’s syndrome (gonadal dysgenesis)
Male equivalent is klinefelters - High GnRH, high LH/FSH, low estrogen/progesterone
What are anatomical causes of primary amenorrhoea and other causes.
- Mullerian agenesis - agenesis of uterus and upper 2/3 of vagina
- Imperforate hymen
- Vaginal atresia - vagina closed or absent
- Transverse vaginal septum
- Congenital adrenal hyperplasia - 17 alpha hydroxylase deficiency
Normal GnRH, LH/FSH, Estrogen/progesterone
Characteristics of turner syndrome
- Most common cause of ovarian dysgenesis and primary ovarian insufficiency - hypergonadotropic hypogonadism (high GnRH, high FSH/LH, low estrogen/progesterone)
- Commonly characterized by other clinical manifestations such as short stature, neck webbing, shield chest (broad chest with widely spaced nipples) recurrent otitis media with hearing loss, aortic coarctation, and bicuspid aortic valve. aortic dissection/rupture, osteoporosis and pathological fractures
- The diagnosis of Turner syndrome may be made with a karyotype: 45,XO; no Barr body)
Pathophysiology: chromosomal nondisjunction → X chromosome monosomy/mosaicism → impaired ovarian development → malfunctioning streak gonads with connective tissue instead of normal germ cells → estrogen and progesterone deficiencies
What are conditions associated with Turners?
- Gonadoblastoma (especially in patients with 45,XO/46,XY mosaicism)
- Malformations of the kidney and ureters (especially horseshoe kidney)
- Hashimoto thyroiditis
- Type 2 diabetes mellitus
Treatment for turners
- Estrogen and progestogen substitution
- Growth hormone (GH) therapy
- Surgical removal of streak gonads
Clinical features of turners
- Sex development Female phenotype Primary ovarian insufficiency with: - Delayed puberty - Primary amenorrhea - Infertility: Pregnancy is still possible via IVF using donor oocytes and exogenous estradiol 17β and progesterone (similar rates of success to those in the general population).
Lymphatic system abnormalities
- Cystic hygroma
- Lymphedema of the hands and feet in the neonatal period
Musculoskeletal findings
- Short stature: due to the presence of only one copy of the SHOX (short stature homeobox) gene, normally located on the X chromosome
- Shield chest: broad chest with widely spaced nipples
- Webbed neck: skin folds along the side of the neck between the mastoid process and the acromion
- Cubitus valgus: deformity of elbow in carrying angle
- Short fourth metacarpals/metatarsals, nail dysplasia
- High arched palate
- Low-set posterior hairline
- Osteoporosis and pathologic fractures
Cardiovascular abnormalities
- Bicuspid aortic valve: increased risk of premature aortic stenosis and/or insufficiency
- Coarctation of the aorta with brachial-femoral delay
- Aortic dissection and rupture
- Hypertension (even in children)
Other disorders
- Gonadoblastoma (especially in patients with 45,XO/46,XY mosaicism)
- Malformations of the kidney and ureters (especially horseshoe kidney)
- Hashimoto thyroiditis
- Type 2 diabetes mellitus
Investigations for amenorrhoea
- Pregnancy test
- Check for secondary sexual characteristics and anatomical anomalies (physical examination, pelvic ultrasound).
- Uterus absent: Perform karyotyping and serum testosterone to investigate for male/female genotype and androgen sensitivity.
- Uterus present: Test FSH and LH levels.
- Exclude imperforate hymen, vaginal atresia, and transverse vaginal septum.
- ↑ FSH: primary ovarian insufficiency (e.g., Turner syndrome, Swyer syndrome, premature ovarian failure)
- Normal or ↓ FSH: constitutional growth delay, hypogonadotropic hypogonadism
- If galactorrhea is present: Check prolactin and TSH levels.
- If symptoms of hyperandrogenism are present:
- Check serum testosterone and dehydroepiandrosterone sulfate (DHEA-S).
- If high: Suspect an androgen-secreting tumor.
- If blood pressure is high: Suspect congenital adrenal hyperplasia.
- Abnormal levels of prolactin and/or TSH support a nonovarian cause of amenorrhea.
- Elevations of FSH and LH levels in the presence of a low estradiol level support the diagnosis of POI (primary ovarian insufficiency).
What are the causes of secondary amenorrhoea.
○ Pregnancy: most common cause of secondary amenorrhea
○ The most common hormonal cause of secondary amenorrhea is polycystic ovary syndrome (PCOS), which accounts for 40% of cases. Additional hormonal causes of secondary amenorrhea include hypothalamic amenorrhea (hypogonadotropic hypogonadism), hyperprolactinemia, thyroid disease, and premature ovarian insufficiency (POI) (hypergonadotropic hypogonadism).
○ Ovarian disorders (e.g., premature ovarian failure, polycystic ovary syndrome )
○ Medications (antipsychotics, chemotherapy, oral contraceptives)
○ Hypothyroidism (↓ T3/T4 → ↑ TRH → ↑ prolactin → ↓ GnRH → ↓ estrogens): cause secondary amenorrhoea through increased TRH causing stimulation of prolactin secretion.
○ Hyperthyroidism
○ Hyperprolactinemia: causes secondary amenorrhoea through direct inhibition of GnRH secretion.
○ Sheehan syndrome
○ Asherman syndrome
§ Structural cause of secondary amenorrhoea
§ Uncommon complication of dilation and curettage, intrauterine device placement or surgical procedures such as hysteroscopic myomectomy
§ Caused by lack of basal endometrium proliferation and formation of adhesions (synechiae)
§ Diagnosis should be considered in any woman with amenorrhoea and past exposure to uterine instrumentation
§ Classic presentation: amenorrhoea or scant bleeding during periods (hypomenorrhea) with ovulatory symptoms (cervical mucous changes, adnexal tenderness associated with follicle formation) or premenstrual symptoms (mood changes, breast tenderness0>
○ Cushing syndrome
○ Adrenal insufficiency
○ Obesity
○ Hypergonadotropic hypogonadism
○ Hypogonadotropic hypogonadism
○ Functional hypothalamic amenorrhea: a dysfunction in the pulsatile secretion of GnRH
§ Etiology
§ Excessive exercise: e.g., in competitive athletes (also called exercise-induced amenorrhea)
§ Reduced calorie intake (e.g., in eating disorders like anorexia nervosa)
§ Stress
§ Female athlete triad syndrome: menstrual dysfunction, calorie deficit, and decreased bone density in athletic female young adults or adolescents
§ Pathophysiology: decreased leptin (low body fat) and/or increased cortisol (exercise/stress) → decreased pulsatile release of GnRH from the hypothalamus → decreased secretion of FSH and LH → decreased estrogen levels → anovulation and secondary amenorrhea → infertility
Estradiol levels are typically low, and patients may experience vasomotor symptoms and sleep disturbance. If left untreated, patients are at increased risk for osteoporosis owing to this low-estrogen state. Recovery of menses may occur if BM! returns to normal. Cognitive-behavioral therapy for cases caused by emotional stress has been shown to be effective.
How can hirsutism be assessed?
Modified ferriman galway scoring system
9 body areas scored 0-4, scores >4-6 indicate hirsutism
Causes of hirsutism.
Hirsutism is a condition in women that results in excessive growth of dark or coarse hair in a male-like pattern — face, chest and back
Ovarian:
- PCOS
- HAIR-AN: hyperandrogenic insulin‐resistant acanthosis nigricans
- Ovarian tumour, ovarian hyperthecosis
Adrenal:
- Tumour (Cushing’s)
- Late onset congenital adrenal hyperplasia
Other:
- Drugs e.g. anabolic steroids, Te Rx
- Idiopathic – diagnosis of exclusion
- ?Increased target organ sensitivity or 5alpha-‐reductase activity
What are signs of virilisation.
Rapid onset and progression of deepening of the voice, severe acne, clitoromegaly, and male pattern balding are signs of virilization and are concerning for an ovarian or adrenal tumor. Age of onset after 30 years is also a risk factor for an androgen secreting tumor.
Investigations for hirsutism and virilisation
- In patients with hirsutism or virilization, recommended initial laboratory tests include measurement of plasma dehydroepiandrosterone sulfate (DHEAS) level and serum levels of TSH, prolactin, total testosterone, and follicular-phase 17-hydroxyprogesterone.
○ Normal levels exclude adrenal tumors, hypothyroidism, hyperprolactinemia, and ovarian tumor.
○ Common forms of late-onset congenital adrenal hyperplasia, often mistaken for PCOS, can be excluded with a normal 17-hydroxyprogesterone level.
