Lecture 28: Menopause Flashcards
What are 4 possible theories for the earlier onset of reproductive failure (infertility) compared to other body systems in females
- From 1900s life expectancy has gone past 50 – we live longer than the fixed number of follicles
- Deterioration of reproductive processes with age protects aging women from hazards of childbirth
- Menopause protects human gene pool against birth defects due to age related increase in chromosomal abnormalities
- A pause from reproduction enhances the extended maternal care of offspring
What is the reason for menopause and the event that it is measured by; what ages are POI, Early menopause and general menopause
Menopause is caused by exhaustion of the follicular reserve –(>1000 follicles) through atresia and ovulation (over a lifetime = 400) or follicles left are not able to respond to hormones.
It is measured by last menstrual period - amenorrhoea for 12 months (for 45+ woman)
POI: menopause <40 yo
Early menopause : 40-45 yo
General: 50-52 yo
What is the main reasons for follicle loss between 7 mil at 6 mo gest to 1.2 mil at birth
Loss of defective follicles that cannot form the primordial follicle
As the quantity of follicles declines….
popcorn hypothesis
+ why?
As the quantity of follicles declines the quality of follicles also decreases.
This is because follicles with the most FSH receptors, blood supply are ovulated earlier than those with chromosomal abnormalities. These require higher levels of FSH stimulation (from loss of inhibin feedback) to be ovulated
What are factors that affect the timing of menopause and which factors are independent
1st nutrition: poor nutrition results in earlier menopause. Smoking results in earlier menopause (1-2 ys caused by toxicity to primordial follicles)
Independent factors (In well nourished populations) is ethnicity, parity and age of menarche
What is Andropause , what age group, and how does it present
The slight decline of T2 in men 40-55yo.
The bodily changes occur gradually: accompanied by changes in attitudes, moods, fatigue, low sex drive, low physical agility.
Describe the 5 phases associated with end of reproductive life of a woman and the timings/ events
- Around 40 : Pre-menopause: continued regular cycles
- 4-6 years before Menopause: Menopausal transition- cycles become irregular (usually longer as there are some non-ovulatory cycles)
- This is the start of Peri-menopause, which goes until the start of ovarian senescence: The start of menopausal symptoms. - Menopause (LMP) at 50 yrs – after this is the post menopause time period
- 1-2 years after menopause: Ovarian senescence: complete stop of ovarian hormone production
What are the changes in the follicle levels during Perimenopause (including hormones) – what is the first sign
- Follicle levels reduce below critical threshold- 25000
- Inhibin B levels start to decline (due to less granulosa cells of primary follicles)
- Due to reduced negative feedback on FSH, there is (smaller increase in LH) and increase in FSH:
The First Sign of Perimenopause - also seen in POI as well
- After which there is acceleration of follicle loss
What are the main reasons for acceleration of follicle loss in peri-menopause and what are the side effects seen clinically
- Increased FSH ->
- stimulate greater proportion of primordial follicles to enter the growing pool
- responsible for higher rates of twinning due to dominance processes not working as well. - Causes shortened follicular phase
- Increased follicular E2 in early perimenopause but are sometimes low (late).
- Fluctuations responsible for moodswings.
What are the challenges around contraception during perimenopause
Due to irregular cycles and unpredictable hormone patterns, contraception is difficult because ovulation is always possible but annovulatory cycles are common
Compare the sources of E2, amount circulating and variation between ovarian senescence and Pre menopause
Ovarian senescence:
The amount of estradiol produced daily is less than 1/10th of previous so circulating levels are very low and show little variation from day to day.
This is the same for Oestrone but there is slightly less dramatic.
This is because the main source of E2 post menopause is Oestrone made from conversion of adrenally produced Androstenedione in adipose
Pre menopause women also get this but also get secretion of estradiol from ovary and conversion of ovarian androstenedione by adipose as well
What are 6 perimenopausal symptoms caused by the estrogen (and maybe progesterone) deprivation
- Vasomotor: reduction of E2 acting on bv
- hot flushes, night sweats, assoc with palpitation, weakness, - GU symptoms of vaginal dryness due to
- decline in epithelial growth, elasticity, atrophic changes, reduction in vaginal lubrication, rise in pH.
Can lead to dyspareunia, incontinence, recurrent UTIs - Reduction in size of uterus, reduced breast density
- Bone metabolism: increased catabolism- increased risk of osteoporosis
- Blood lipid changes which increase CVS risk
- Behavioural/psychological changes : depression, tension, anxiety, mental confusion,
loss of libido (due to reduced ovarian androstenedione
What is the treatment offered for women with moderate to severe menopausal symptoms and what dose is chosen and why
Hormone replacement therapy: to replace estrogen
HRT should be at the lowest dose for shortest time necessary to control symptoms and then weaned off. This is bc of increased CVS, alzheimers, breast and uterine cancer risk (compared to osteoporosis protective effects)
What are other conditions where a fast onset of menopause is achieved
- very challenging bc?
Prophylactic Breast and Ovary removal as well as chemotherapy for cancer
- have all the perimenopausal symptoms immediately but are not able to take HRT bc of possible relapse of cancer
