Mojab menopause/ HRT

Question 1

Describe the hormonal changes occurring during the follicular phase of the menstrual cycle

Answer 1

1. Menses begins due to a dramatic drop in estrogen and progesterone, removing negative feedback on the hypothalamus and anterior pituitary.
2. FSH levels rise slightly on day 1, stimulating the recruitment and growth of multiple follicles.
3. LH levels remain relatively stable early on but begin to rise gradually, stimulating theca interna cells to convert cholesterol to androstenedione.
4. Granulosa cells of the developing follicles express aromatase, converting androstenedione into estradiol (estrogen).
5. By day 5–7, a dominant follicle is selected, which begins producing increasing levels of estrogen.
6. Rising estrogen exerts negative feedback on the anterior pituitary, causing FSH levels to fall. This is reinforced by inhibin B, secreted by the dominant follicle, which further suppresses FSH and prevents other follicles from maturing.
7. Around days 5–8, LH levels begin to surpass FSH levels due to positive feedback from increasing estrogen.
8. When estrogen reaches a critical threshold, it switches from negative to positive feedback on the hypothalamus and anterior pituitary, triggering the LH surge (~24–36 hours before ovulation).
9. Ovulation occurs ~36 hours after the LH surge begins (typically around day 14), marking the transition to the luteal phase.

Question 2

Describe the hormonal changes during the luteal phase

Answer 2

1. Progesterone dominates the luteal phase and rises steadily due to the formation of the corpus luteum from the remnants of the ruptured follicle.
2. Progesterone levels peak around mid-luteal phase (~days 21–23), which aligns with the optimal window for implantation (if fertilization has occurred).
3. Estradiol initially drops post-ovulation but rises again mid-luteal phase due to moderate production by the corpus luteum alongside progesterone.
4. FSH and LH levels decline gradually due to negative feedback from progesterone, estradiol, and inhibin A, all secreted by the corpus luteum.
5. The corpus luteum will degenerate into the corpus albicans by the end of the luteal phase (~day 28), unless hCG is produced by syncytiotrophoblasts to maintain it during early pregnancy.

Question 3

Define fibroid and polyp

Answer 3

Fibroids are benign tumours of the uterus primarily composed of smooth muscle and fibrous connective tissue.

A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated; if it is attached without a stalk, it is said to be sessile.

Question 4

Explain how annovulation can cause dysfunctional uterine bleeding

Answer 4

*Lack of ovulation means no corpus luteum formation meaning no progesterone secretion.

*Estrogen continues to be produced, no longer following its usual cyclical pattern and is now unopposed by progesterone.

*Estrogens proliferative effects on the endometrium continue in the absence of progesterone’s stabilizing effects resulting in an unstable and fragile endometrial lining which soon outgrows its blood supply.

*Instability is further compounded by: increased plasmin and matrix metalloproteinase levels in the absence of progesterone.

*Shedding of the endometrial lining eventually occurs and may be irregular, prolonged or heavier than normal

Question 5

Explain the reason for giving tranexamic acid to someone with DUB

Answer 5

Tranexamic acid (TXA) is an antifibrinolytic drug that competitively inhibits plasminogen activation, preventing its conversion to plasmin and thus reducing fibrin clot degradation.

In anovulatory DUB, estrogen is unopposed by progesterone, leading to continuous endometrial proliferation without stabilization.

Progesterone normally upregulates plasminogen activator inhibitor-1 (PAI-1), which limits plasmin formation. In its absence, PAI-1 levels decrease, leading to excess plasmin activity.

Elevated plasmin levels cause premature fibrin breakdown, leading to unstable clot formation within the endometrial microvasculature and irregular or heavy bleeding patterns.

By inhibiting plasmin activation, TXA helps stabilize endometrial clots, reducing menstrual blood loss by 40–50% in heavy menstrual bleeding associated with DUB.

Question 6

Describe 3 effects of estrogen on lipid metabolism

Answer 6

1. Lowers Serum LDL:
Estrogen upregulates hepatic LDL receptor expression, increasing LDL clearance by hepatocytes and reducing circulating LDL-cholesterol levels, thereby lowering the risk of atherosclerosis.

2. Increases HDL Levels:
Estrogen stimulates Apolipoprotein A1 (ApoA1) gene expression, the main structural protein of HDL. This enhances reverse cholesterol transport, where excess cholesterol is removed from tissues and transported to the liver for excretion.

3. Regulates Triglyceride Metabolism:
Estrogen stimulates hepatic triglyceride synthesis while simultaneously promoting triglyceride clearance by increasing lipoprotein lipase (LPL) activity in adipose and muscle tissues. This facilitates the uptake and utilization of triglycerides.

This dual effect helps maintain normal triglyceride levels and prevents excessive lipid accumulation.

Question 7

Describe 4 ways that estrogen promotes bone health

Answer 7

1. Inhibits osteoclast activity by downregulating RANKL expression and upregulating OPG release.
2. Promotes osteoblast proliferation and differentiation through enhancing TGF-beta and bone morphogenetic proteins
3. Enhances availability of vitamin D thereby increasing efficiency of calcium absorption
4. Promotes synthesis of calcitonin to regulate blood calcium levels by inhibiting osteoclasts and promoting renal excretion of calcium

Question 8

Name 3 ways in which estrogen has a protective effect on the CVS

Answer 8

1. Enhances endothelial function by promoting nitric oxide synthesis –> vasodilation and improved blood flow.
2. Reduces vascular inflammation thereby decreasing the risk of atherosclerosis.
3. Antioxidant effects include enhancing mitochondrial activity and reducing reactive oxygen species production thereby reducing oxidative stress in CVS tissues.

Question 9

Describe the hormonal changes that occur throughout perimenopause

Answer 9

Early Perimenopause: Decreased inhibin → fluctuating FSH → fluctuating estrogen levels due to some residual ovarian function.

Late Perimenopause: Further loss of follicles → decrease in inhibin is more pronounced→ increased FSH → low estrogen levels.

**FSH levels may still be within the normal range but at the higher end in early perimenopause.

Day 2-5 FSH levels should normally be low because of the feedback from rising estrogen levels. However, a high FSH level during Day 2-5 (when measured in the setting of recent months of amenorrhea or irregular periods) can indicate perimenopause, as the ovaries’ reduced response to hormonal signals results in a higher FSH secretion.**

Question 10

Name 4 indications for endometrial biopsy

Answer 10

(1) AUB > 45yo
(2) Abnormal cervical smear
(3) Post menopause bleeding
(4) Surveillance of a prev diagnosed endometrial hyperplasia
(5) AUB < 45 with risk factors e.g. obesity, persistent/ refractory AUB, Lynch syndrome, tamoxifen use, chronic ovulatory dysfunction

Question 11

Name 4 types of hysterectomy

Answer 11

1. Total: Uterus and Cervix removed
2. Subtotal: Uterine body only is removed, cervix left.
3. Total + bilateral salpingo-oopherectomy: uterus, cervix, tubes, ovaries
4. Radical: uterus, cervix, parametrium, vaginal cuff, tubes, +/- ovaries

Question 12

Name 4 indications for hysterectomy

Answer 12

1. Heavy menstrual bleeding refractory to other treatment options
2. Malignancy
3. Uterine prolapse
4. Post partum haemorrhage (life saving treatment)
5. Risk reducing sx for genetic predisposition to malignancy e.g BRCA 1+2 / Lynch syndrome

Question 13

Name 4 pieces of advice that should be given on discharge after hysterectomy

Answer 13

1. No strenuous activity / lifting heavy objects for 4-6 weeks.
2. No sexual intercourse for 4-6 weeks.
3. Maintain light physical exercise to avoid thromboembolism
4. Keep surgical site clean, dry and educate on signs of wound dehiscence
5. Discuss HRT if ovaries removed
6. Report heavy vaginal bleeding/ discharge

Question 14

Differentiate between type 1 and type 2 endometrial cancer

Answer 14

Type I endometrial cancer, also known as endometrioid adenocarcinoma, is estrogen-dependent and typically arises in the setting of chronic unopposed estrogen exposure, often through endometrial hyperplasia. It is generally well-differentiated, less aggressive, and commonly associated with PTEN mutations and microsatellite instability. It accounts for approximately 80% of endometrial cancers.

Type II endometrial cancer includes non-endometrioid subtypes such as serous, clear cell, and carcinosarcoma. It is estrogen-independent, tends to arise in older, postmenopausal women with an atrophic endometrium, and is typically high-grade and more aggressive. TP53 mutations are frequently observed.