Menstrual Disorders Flashcards
Definition of primary amenorrhea
Failure to establish menstruation by age 15
Hyperprolactinaemia causes
Medications
- antipsychotics
- Phenothiazines
- metoclopramide
- TCAs
Functional
- pregnancy, stress
Pituitary micro (<10mm) or macro (>10mm) adenoma
Pituitary stalk compression/ disruption thus interfering with the normal suppression of prolactin by hypothalamic dopamine
Hypothyroidism
Chronic renal failure due to decreased excretion of prolactin
Clinical evaluation for hyperprolactinaemia
MRI head- look for pituitary lesion/ CNS lesion
Assessment of visual fields
Bloods: renal function, thyroid function
PCOS pathophysiology
Raised ovarian androgen levels due to:
- extra- ovarian production of androgens
- high LH levels resulting in increased stimulation of theca cells which then secrete more androgens
- decreased levels of sex hormone- binding globulins (SHBG) so despite having normal LH and androgen levels, there’s more free circulating (active androgens)
- increased insulin levels- which augments the activity of LH and stimulates the adrenal glands to increase production of extra- ovarian androgens and reduced production of SHBG
The increased androgen levels:
- disrupt folliculogenesis resulting in multiple small follicles and increased levels of follicular atresia- giving rise to poly cystic appearance
- acts peripherally to cause signs of hyperandrogenism
- interfere with hypothalamic feedback loop resulting in loss of pulsatile GnRH secretion, causing disturbed LH and FSH secretion. Low levels of FSH contributes to failure of dominant follicle development, thus no LH surge to cause ovulation (anovulation). Failure to develo corpus luteum leads to low levels of progesterone (oligomenorrhoea).
DHEA levels
Marker of adrenal androgen production. If raised could be associated with adrenocortical tumour
Androstenedione
Elevated levels may be associated with ovarian androgen- secreting tumour
What is the Ferriman- Gallwey Scoring system
Assess 9 body areas sensitive to androgens and are assigned a score from 0 (no hair) to 4 (virile or extensive hair growth)
Assesses:
- upper lip
- chin
- chest
- abdomen
- pubic hair
- upper arms
- thighs
- upper back
- lower back/ butt
A score of 1-7 is focal hirsutism and is a normal variant
Describe the follicular phase of the menstrual cycle
The follicular phase varies in length depending on the length of the cycle.
At the start of the menstrual cycle (day-1), the hypothalamus secretes GnRH in pulses. GnRH then stimulates the anterior pituitary to release FSH and LH.
FSH stimulates proliferation of the granulosa cells and the formation of zona pellucida (primary follicles develop into the secondary follicles).
Small follicles secrete inhibin B which feeds back and inhibits basal FSH secretion.
Theca cells surrounding the granulosa cells respond to LH by increasing the number of LDL receptors and cholesterol entry into cells, and activation of p450 leading to increased androgen (androstenedione) production.
FSH then stimulates the aromatase enzymes which converts androgens to oestrogen (17b oestradiol) within the granulosa cells.
As the follicles grow, they secrete increasing amounts of oestradiol which relies on both FSH and LH. The increasing amount of oestradiol exerts negative feedback to the hypothalamus and anterior pituitary causing FSH levels to drop. The smaller follicles need more FSH to grow so they regress and undergo atresia, leaving the largest (dominant) follicle to survive.
Ovulation phase of the menstrual cycle
At mid cycle, as blood oestrogen levels peak, it exerts positive feedback to the hypothalamus and anterior pituitary to release more LH= LH surge, 36 hours prior to ovulation.
The LH surge:
- activates the follicle/ secondary oocyte and it enters metaphase of meiosis 1.
- activates a cascade of processes which thins the follicle wall, leading to the release of oocyte (ovulation) 36 hours later. Prostaglandin is a key regulator in this step.
- luteinizes the granulosa cells, giving them the enzymatic machinery to synthesise progesterone in response to LH stimulation. This process is not dependent on prostaglandins.
Luteal phase of the menstrual cycle
This phase is always 14 days before the menses regardless of the length of periods.
Following ovulation, the remaining granulosa cells and theca cells form the corpus luteum- could be up to 20mm.
The CL produces large amounts of progesterone in response to LH.
As the CL matures, it becomes less sensitive to LH, progesterone secretion declines and the CL begins to disappear from the ovary.
The CL secretes inhibin A and oestradiol in addition to progesterone. These exert negative feedback to inhibit FSH secretion during the luteal phase.
Pathophysiology of fibroids
Fibroids are a mixture of smooth muscle cells and fibroblasts, which form hard, round, whorled, monoclonal tumours in the myometrium.
Oestrogen and progesterone control the proliferation and maintenance of uterine fibroids. The primary action of oestrogen is thought to be mediated through induction of progesterone receptor expression, thereby allowing leiomyomas to respond to progesterone.
Most medical therapy act by inhibiting the production of sex steroids or their action
Risk factors for fibroids
Increased oestrogen exposure:
Early menarche
PCOS
obesity
COCP
Nulliparity
Race
Hereditary/ genetic
DES exposure
Prior uterine infection
Physical and sexual abuse
Mechanism for AUB with fibroids
Abnormal vasculature
Impaired endometrial haemostasis
Dysregulation of angiogenic factors
Increased surface area
Altered uterine contractility
Mechanism for pain with fibroids
Altered uterine contractility
Degeneration
Increased bleeding and clots
Mechanism of action for infertility/ Obs complications with fibroids
Distortion of the uterine cavity
- increased miscarriage
Altered endometrium overlying fibroid
Changes in uterine contractility
- increased bleeding/ PPH
