Menstrual Cycle and its Hormonal Cycle

Question 1

Menarche

Answer 1

End of puberty and marks the beginning of potential fertility.

Maturation of Gonadotrophin Releasing Hormone (GnRH) pulsatility so primarily hypothalamic.

Question 2

Menopause

Answer 2

Occurs around 45-55 years old (average is 51) and marks the end of natural fertility. “Exhaustion” of primordial follicles so primarily ovarian.

Question 3

Theca Cells

Answer 3

Superficial layer of follicle, has LH receptors, converts cholesterol into pregnenolone and can further produce androstenediol and testosterone.

Question 4

Granulosa Cells

Answer 4

Deep to Theca, layer increases in size markedly during primary follicle development when compared with secondary follicle development. Has LH and FSH receptors. Also converts cholesterol into pregnenolone and activates aromatase to transform testosterone into estradiol/ Androstenedione to estrone.

Question 5

Hypothalamic-Pituitary-Ovarian Axis

Answer 5

Gonadotrophin Releasing Hormone (GnRH)/Luteinising Hormone Releasing Hormone (LHRH) is secreted by small body neurons in the arcuate nucleus and preoptic area of the hypothalamus. It is secreted into the Median Eminence and Hypophyseal Portal System. It binds to receptors on Gonadotrophic cells of the Anterior Pituitary. Leads to Follicle-Stimulating Hormone and Luteinising Hormone.

GnRH neurons release GnRH in rhythmic pulses around 1 per hour. GnRH has a half-life in blood approx. 2-4mins. Theca cells have LH receptors and Granulosa Cells have LH and FSH receptors.

Question 6

Negative VS Positive Feedback

Answer 6

During most of the cycle, oestrogens and progestins have a negative feedback on pituitary and hypothalamus to reduce FSH and LH production.

However, near ovulation/end of follicular phase, positive feedback occurs. Oestradiol levels gradually increase after reach of a certain threshold for a minimum of 2 days, hypothalamus axis reverses its sensitivity to oestrogens. This leads to strong oestrogen positive feedback. Increased sensitivity of anterior pituitary to GnRH leads to LH surge.

Question 7

Activins

Answer 7

Peptide hormone produced by ovaries which activates FSH and increases FSH mRNA levels (does not affect LH mRNA levels).

Question 8

Inhibins

Answer 8

Peptide hormone produced by the ovaries which inhibits FSH and reduces FSH mRNA levels (does not affect LH mRNA levels).

Question 9

Follistatins

Answer 9

Peptide hormone which is produced by the ovaries. Binds to activins inactivating them, so indirectly inhibits FSH.

Question 10

Roles of Oestradiol

Answer 10

• Prepare female reproductive tract for fertilisation and implantation.
• Induces expression of progesterone receptors in target tissues (required for corpus luteum).
• Tubal epithelium - Stimulates proliferation of epithelial lining and secretes sugar-rich fluid.
• Endometrium - stimulates hyperplasia and hypertrophy of epithelial lining, glands elongate and spiral arteries grow.
• Smooth muscle - upregulates receptors for prostaglandins and oxytocin, spontaneous activity increased.
• Cervix - increases mucous volume and decreases mucous viscosity.

Question 11

Roles of Progesterone

Answer 11

• Prepare female reproductive tract for fertilisation and implantation.
• Tubal epithelium - reduces proliferation of epithelial lining and reduces secretion of sugar-rich fluid.
• Endometrium - stimulates secretory phase menstrual cycle and stimulates further growth and secretion from glands
• Smooth muscle - reduces sensitivity to oxytocin by downregulating receptors and brings about relaxation of smooth muscle in reproductive tract and elsewhere.
• Cervix - reduces mucous volume and increases its viscosity.

Question 12

Oligomenorrhoea

Answer 12

infrequent light periods

Question 13

Metrorrhagia

Answer 13

irregular bleeding

Question 14

Dysmenorrhoea

Answer 14

painful periods e.g. menstrual cramps. Main cause is overproduction of prostaglandins by endometrium in response to decreased plasma oestrogen and progesterone. Leads to excessive uterine contractions. Prostaglandins can also affect smooth muscle elsewhere and cause other systemic symptoms e.g. nausea, vomiting, and headache.

Question 15

Polymenorrhoea

Answer 15

frequent periods

Question 16

Premenstrual Syndrome (PMS)

Answer 16

3/4 women have cyclical symptoms which can affect the quality of their lives to a greater or lesser extent. Symptoms include; anxiety, mood swings, tiredness, irritability, depression, loss in confidence, clumsiness, headaches, feeling bloated, change in appetite, joint pain, tender enlarged breasts and abdominal pain. Progesterone has anxiolytic (anti-anxiety) effect, therefore a fall in progesterone levels at the end of the cycle could be the cause of PMS.

Question 17

Amenorrhoea

Answer 17

No periods. Primary causes include anatomical/congenital abnormality (underdevelopment or absence of uterus/vagina) or genetic (Turner’s Syndrome). Secondary causes include pregnancy, lactation, exercise/nutrition, menopause, polycystic ovarian syndrome, iatrogenic (surgery, medication). Symptoms include hot flushes and vaginal dryness due to oestrogen deficiency and loss of bone mineralisation (osteopenia/osteoporosis).

Question 18

Premenstrual Dysphoric Disorder (PMDD)

Answer 18

a more disabling version of PMS, occurs in 3-8%.

Question 19

Therapeutic Uses of Gonadotrophin Releasing Hormone (GnRH)

Answer 19

• Continuous administration of GnRH causes suppression of gonadotrophin secretion.
• Endometriosis - common condition with growth of endometrial tissue outside the uterine cavity. Tissue responds to oestrogens of menstrual cycle and results in pain and infertility. Continuous administration of GnRH analogue inhibits gonadotrophin secretion and reducing oestrogen levels, leading to reduced endometriotic tissue.
• IVF - GnRH analogues used before controlled IVF cycle commences.

Question 20

Birth Control Pills

Answer 20

• Fixed combination oral contraceptive pill (OCP) - 50/50 oestrogen and progestin
• Varying dose OCP - 2 or 3 different dosages of oestrogen and progestin.
• Progestin-only “mini-pill” OCP

Contraceptive steroids feedback on hypothalamic neurons and gonadotrophin cells and suppress LH and FSH secretion (so no follicular development or LH surge/ovulation). Progestin effect causes cervical mucous thickening and increase viscosity, reduces uterus and oviduct motility, endometrial changes (inhibits sperm penetrationa nd reduces chances of implantation)

Question 21

Premature Ovarian Failure (POF)

Answer 21

Menopause can occur in women under the age of 40 (idiopathic, autoimmune disorders, genetic disorders such as Fragile X, chemotherapy, radiation). Symptoms can be treated with Oestrogen Replacement (hormone replacement therapy - HRT).

Question 22

Follicular Phase of the Ovarian Cycle

Answer 22

Between days 0 and 14 of ovarian cycle. When the follicle develops. Oestradiol, FSH and LH peak in this phase.

Question 23

Ovulation

Answer 23

Approx day 14. LH surge just before to start ovulation. Ovum is released from follicle.

Question 24

Luteal Phase of the Ovarian Cycle

Answer 24

Between days 14 and 28 of ovarian cycle. Corpus luteum develops. Progesterone and Inhibin peak in this phase.

Question 25

Menstrual Phase of the Endometrial Cycle

Answer 25

• Between days 0 and 7 of endometrial cycle. All hormones at baseline level. Gets rid of lining during this phase.

Question 26

Proliferative Phase of the Endometrial Cycle

Answer 26

Between days 4 and 14 of menstrual cycle. Divided into early (days 4-8/9) and Advanced (day 8/9 to 14). Early proliferative stage is when the endometrial lining is at its thinnest. During the advanced stage, the functional layer of endometrial lining grows. LH surge, Oestradiol and FSH peaks occur in this phase.

Question 27

Secretory Phase of the Endometrial Cycle

Answer 27

Between days 14 and 28 of endometrial cycle. Divided into 3