Gynecology Flashcards
Name the different stages of the menstrual cycle in regards to the ovaries, endometrium,
Ovaries: follicular phase then luteal phase
Endometrium: prolifertive phase (mainly under the effect of oestrogen, secretory phase (progesterone) and menstrual phase
How does GnRH produced by the hypothalamus reach the anterior pituatry?
Hypothalamo-hypophyseal portal circulation
What determines how much pulsatile GnRH is released?
Steroid levels in the blood
What are the different stages of a follicle?
- Primordial follicle (ovum and flattened Granuloma cells)
- Pre Antral follicle
- Antral follicle (development of theca cells)
- Preovulatory (mature)/ Graafian follicle (18-22mm)
Describe the ovarian cycle and how different hormone levels affect it in a 28 day menstrual cycle that does not end with fertilization.
Day 1: menses.
Since corpus luteum of previous cycle has degenerated, hypothalamus detects low levels of steroids (oestrogen and progesterone) and stimulates the pituatry gland to release FSH and small amounts of LH. FSH stimulates follicular growth, and LH stimulates theca cells to produce androstenedione. FSH stimulates the Avascular granulosa cells to convert androstenedione into estradiol. E2 Promotes development of FSH receptors on granulosa cells ans acts with FSH to increase LH receptors on the granulosa cells in the luteal phase. The increasing E2 causes negative feedback on FSH, decreasing the level of FSH allowing only the mature follicle with the highest amount of FSH receptors to grow. The preovulatory rise in FSH increases the ovarian LH receptors to allow a normal luteal phase. Inhibin produced by the granulosa cells also has a negative feedback on FSH. Inhibin also enhances LH-induced androgen synthesis. Therefore; allowing the dominant follicle to continue its growth and causing atresia of other follicles. Once the level of E2 reaches its “critical level” it causes a positive feedback on LH and we get what is called the LH surge. This LH surge results in the completion of the reduction division in the oocyte. Granulosa and theca cells become luteinized. Granulosa cells become vascular, get cholesterol, carotene, phospholipids and start producing oestrogen, progesterone, prostaglandins. Prostaglandins and proteolytic enzymes are responsible for the digestion and rupture of the follicle wall. Therefore, around 12-24 hours after LH surge, ovulation occurs. This happens around day 14 of the cycle. The Graafian follicle then becoems the corpus luteum that secretes oestrogen and progesterone, and is maintained by LH. progesterone reaches its highest level at mid luteal phase (day 22). High steroid hormones cause a negative feedback on pituatry gonadotropins. Corpus luteum can no longer maintains, undergoes fibrosis and becomes the corpus albicans which no longer releases hormones. Sudden drop in hormones = endometrium is no longer maintained= menses.
What if fertilization does occur?
The blastocyst secretes human chorionic gonadotropin from the trophoblastic cells. This has an LH like function so maintains the corpus luteum for 3 months until placenta formation is complete in order to maintain a high level of oestrogen and progesterone to support the endometrium.
Describe the cervical mucous in the first half of the cycle, under the effect of oestrogen
• Profuse
• Watery
• Contains Nacl, Kcl.
• Acellular.
• +ve Spinnbarkeit (thread 7-10 cm)
• +ve Fern test
• Parallel arrangement of mucus strands
Describe the proliferative phase of the endometrium under the effects of oestrogen
Starts just: After menstruation.
Ends with: Ovulation.
Duration: Variable, (in any cycle, the luteal phase is a fixed 14day phase, and the follicular phase changes).
Effective form: estrogen produced by a follicle stimulates proliferation of the epithelium.
Endometrial changes:
- Thickness: increases gradually to reach 3-4 mm just before ovulation.
- Glands: are straight and tubular, no secretions.
- Stroma: the stromal cells increase in number and size, with little cytoplasm.
- Vascularity: increases gradually.
Describe the secretory changes of endometrium under the effect of progesterone
Starts with: Ovulation.
Ends with: Onset of menstruation.
Duration: Fixed, about 14 days whatever the length of the cycle (life span of the C.L). P & E (from CL) stimulate more growth & initiate secretory changes.
Endometrial changes:
Thickness: reaches 6-8 mm just before menstruation
Describe menstruation and its changes
Glands:
- Become tortuous with saw-toothed appearance.
-Secretions start to appear as sub nuclear vacuoles which then pass towards the lumen.
Stroma:
- Become oedematous and more cytoplasm appears in the cells.
-Leucocytic infiltration occurs 2-3 days before menstruation. Vascularity: is markedly increased.
Two types of arterioles: Spiral and Short straight: supplying the basal endometrium.
►If pregnancy occurs, the secretory changes will become more marked, the endometrium then becomes the decidua of pregnancy. Menstrual phase: (menstruation)
Periodic and cyclic shedding of the superficial layers of the endometrium with variable amount of blood (average: 30-80cc).
Menstrual discharge consists of blood, leucocytes, and endometrial shreds cervical mucus & desquamated vaginal epithelium.
Mechanism of menstruation:
- Progesterone and estrogen withdrawal occurs due to degeneration of the CL.
- The endometrium shrinks, arterioles are shortened by tightening their coils retarding the circulation resulting in ischemic necrosis of the superficial layers of the endometrium.
- Shedding of necrotic superficial layers occurs while the basal layer is not involved as it is supplied by straight arterioles arising from the main arterioles. Menstrual phase: (menstruation)
Control of the menstrual blood loss:
-The degenerating superficial layers of the endometrium release PGs (mainly PGs F2α) which control blood loss through VC (mainly) & myometrial contractions.
Clotting:
- Menstrual blood is not clotted unless bleeding is excessive.
-Clotting first occurs in the uterine cavity, the clot is dissolved by fibrinolytic enzyme produced by the endometrium at menses.
-If bleeding is excessive, the amount of fibrinolysins available is insufficient and so clots are passed during menses.
Hypothalamic causes of an ovulation?
Functional:
- Emotional stress.
- Excessive stressful exercise.
- Marked weight gain, or loss as “Anorexia Nervosa”.
• Congenital disorders:
- Kallmann’s Syndrome (absent GnRH).
• Organic Lesion:
- Brain Tumors, malformation, or excessive brain disease.
- Iatrogenic as From Surgical procedure , or irradiation.
Pituitary causes of an ovulation?
Pituitary Adenomas:
-Prolactinomas: (prolactin secreting tumors, causing hyperprolactinemia)
-Acidophil adenoma: (GH secreting Tumors, causing Gigantism or Acromegaly)
-Basophil adenoma: (ACTH secreting Tumors, causing Cushing syndrome)
• Empty Sella Syndrome (causing hyperprolactinemia)
• Pituitary Insufficiency (like In Sheehan Syndrome)
Ovarian causes of anovulation?
• Polycystic Ovarian Syndrome. (Commonest)
• Premature Ovarian Failure.
• Bilateral Surgical Removal or Destruction by irradiation.
Endocrinal causes of anovulation?
Thyroid Disorders:
-Hypothyroidism (Due to increase level of TRH).
• Adrenal Disorders:
-Cushing Disease (Due to increased level of cortisol).
Drug induced causes of anovulation?
Oral Combined Contraceptive Pills.
• Progestin therapy.
• Androgenic drugs “Danazol”.
• GnRH Agonists.
• Drugs inducing hyperprolactinemia.
“Psychotropic agents & Anti-emetics”
• Antihypertensive drugs. “Alpha methyl dopa”
• Some Chemotherapeutic agents.
Methods of ovulation detection? (4)
Basal Body Temperature Charts. “BBT” (progesterone has a thermogenic effect)
• Urinary LH Kits.
• Ultrasound folliculometry
• Mid Luteal Serum Progesterone (Peak of progesterone at day 22)
< 5ng/ml = Anovulation
5-10 = Luteal Phase defect
>10 ng/ml = Ovulation
• Premenstrual Endometrial Biopsy (endometrium should be secretory not proliferative)
Management of anovulation?
It is treated mainly according to the patient presenting Complaint.
• Menstrual irregularity:
- Oral Contraceptive pills.
- Progestin.
• Infertility:
- Induction of ovulation.
• Treatment of underlying cause.
- Thyroid disturbance.
- Hyper prolactinemia.
Define luteal phase defect
The inadequate secretory changes of the endometrium during luteal phase, resulting from deficient progesterone production from the Corpus luteum.
Causes of LPD
Inadequate FSH production.
-Hyperprolactinemia.
- Prolonged use of OCPs.
How does LPD manifest?
Spotting at mid cycle
Infertility and recurrent pregnancy loss (endometrium cannot support a pregnancy)
Treatment?
Treat underlying cause or give progesterone in 2nd half of cycle
According to the “Rotterdam Criteria” for diagnosis of PCO, a woman need to have at least 2 out of 3 from the following:?
- Menstrual irregularity (Oligo or hypomenorrhea)
- Evidence of Hyperandrogenism (Hirsutism, elevated serum Testosterone, elevated serum LH)
- Ultrasound Cystic changes of the ovary
Clinical picture of PCO?
Symptoms
Oligomenorrhea (less than 8 cycles /year )
2ry amenorrhea Intermenstrual bleeding Infertility
-Signs: INSULIN RESISTANCE
Obesity
Hirsutism
Metabolic syndrome (hyperlipidemia, CVD, hypertension, DM-II, central obesity)
Laboratory changes in PCO?
triad of ↑LH, ↑Insulin, ↑Androgen)
Inverted LH to FSH ratio (2:1), but with normal FSH levels.
Elevated S. level of LH
• It stimulates more androgen secretion from theca cells
• Inhibit aromatase enzyme responsible for conversion of Ovarian Androgen to Estrogen, thus increasing serum level of ovarian Androgens.
Elevated S. level of Androgen: “Hyperandrogenism”
• Stimulated by high level of LH.
• Atresia in developing follicles leading to Anovulation.
• Hirsutism.
• Excess androgen is converted in peripheral fat cells into Estrone, leading to high levels of unopposed estrogen, which results in Endometrial Hyperplasia
Elevated S. level of Insulin: “Hyperinsulinemia”
• Due to peripheral insulin resistance associated in patients with PCO.
• Leads to impaired oral glucose tolerance test.
• Insulin increase ovarian theca cells sensitivity to LH.
• Decrease Aromatase enzyme activity.
• Decrease production of SHBG.
Describe the appearance of the ovaries in PCO in US and laparoscopy
US: Increased Ovarian size & volume >10 Cm3. necklace appearance, no dominant ovary
Laparoscopy: enlarged ovary, thick glistening capsule, with the absence of ovarian gyrii, giving the image of “Oyster Shell Ovary”
Long term risks of PCO?
Risk for type 2 diabetes mellitus
• Hyperlepidemia
• Cardiovascular disease
• Highly increased risk for Endometrial hyperplasia, and then Endometrial Carcinoma (if untreated properly, due to long period of unopposed Estrogen).
Management of PCOS?
• Life style (Weight loss and Exercise).
• Hormonal therapy: (the aim is regulation of menstrual cycle).
- Combined Oral Contraception.
- Cyclic Gestagen.
• Insulin sensitizing drugs: as Metformin
• Induction of Ovulation (if seeking fertility).
• Surgical laparoscopic drilling (not widely
