Menopause Flashcards
Describe the changes in the number of primordial germ cells in the human ovary from foetal development trhough to old age:
Large amount of primordial follicles developed my mitosis by the 2nd trimerster; this then dramaticall decreases from birth to roughly 500,000-1 million PFs because of naked oocytes/errors in meiosis and mitosis/DNA errors etc to ensure the best quality oocytes remain. This is known as the ovarian follicle reserve.
At puberty, these PFs are activated to become pre-antral follicles by a number of factors; this leads to the continuing depletion of PFs until the menopause, when the primordial follicle reserve depletes completely
What factors affect ovarian reserve?
- nutrition e.g. underweight/overweight
- Expsore e.g. BPA (plasticizers); general environment environments e.g. pesticides
- Prenatal exposure to e.g. androgens (PCOS), cigarette smoking
- Geography/ethinicity/economic factors/eduction
How do hormone levels during the menopause transition?
At menopause, E1/E2 rapidly reduces (to about 30 IU/L) because of the reduced number of follicles expressing LH/FSHRs to synthesise oestrogen.
These lower levels of oestrogen feedback to the Hypo/Pit ERs which triggers negative feedback; as a result, increased FSH and LH levels occurs (FSH very high, upto 75 IU/L)
How can ovarian reserve be predicted?
AMH levels are becoming the gold-standard biomarker to evaluate ovarian reserve and predict ovarian response to stimulation.
pimary and secondary follciles (between primordial and small antral) secrete AMH (which inhibits primordial follicle development and FSH action on other follicles)- this level of AMH can be measured; the more AMH, the higher the ovarian reserve and vice-versa
Describe the differences in AMH over time in men and women:
Men: peak of AMH just after birth; then from puberty, begins high and gradually decreased over age
Women: gradual increase until puberty- rises more in mid-20s and then falls again with age because of depleting ovarian reserve
( The levels of AMH in the human circulation vary during the life cycle, with a sexually dimorphic pattern. Boys (top panel) and men (middle panel) are presented separately, as the mean levels are so divergent. Females produce little or no AMH in utero. The thick lines illustrate the mean levels, and the thin lines the 95% CI. The illustration is based on the following references: Josso et al. (1993), Lee et al. (1996), Schwindt et al. (1997), Rajpert-De Meyts et al. (1999), Rey et al. (1999), Guibourdenche et al. (2003), Oppelt et al. (2005), Aksglaede et al. (2010), Hagen et al. (2010), Grinspon et al. (2011) and Chong et al. (2013). See also Tran et al. (1987), Munsterberg & Lovell-Badge (1991), Hirobe et al. (1992), Taketo et al. (1993) and Al-Attar et al. (1997) for information on mice and rats.)
WHat is AMH important in?
AMH – a novel marker for ovarian reserve
AMH important in folliculogenesis, highest concentrations from 3-4mm follicles , then declines with further follicular growth
What are the hormonal changes during the menopause?
Ovarian senescence begins around 35 years ends with menopause ~51 years.
Decline in ovarian oestrogen largely related to number of primordial follicles, number of recruitable follicles in each ovarian cycle and proportion of follicles that reach adequate maturity
Decline in androgen synthesis in adrenal glands and ovaries
Marked decline in fertility after age of 35 although this depends on ovarian reserve
What can cause premature ovarian failure?
- idiopathic (mostly)- 50%
- autoimmune disorder e.g. addisons
- genetic disorder e.g. fragile x, FSH/LH receptor mutn
- surgery (radiation)- iatrogenic
- environmental
- other causes- gonadal dsy e.g. turners
How can POF be potentially treated…?
……HRT :)
What are the symptoms of menopause?
- hot flashes and night sweats
- vaginal dryness
- sleep disturbance
- mood symptoms
- urinary symptoms (e.g. cough= wee)
What may unopposed oestrogens cause?
Proliferation of the endometrium; not a problem if hysterectomy has taken place though
What HRT preparations exist?
Estrogens
Oral conjugated equine estrogens (CEE) 1.25 mg 0.625 mg 0.3 mg
Oral micronized 17b-estradiol 4.0 mg 2.0 mg 1.0 mg 0.5 mg
Oral estradiol valerate 2.0 mg 1.0 mg
Oral piperazine estrone sulphate 1.25 mg 0.625 mg
Transdermal 17b-estradiol patch 100 μg 50 μg 25 μg 14 μg/day
Subcutaneous implant estradiol 100 mg 50 mg 20 mg
Vaginal
Estriol 1 mg/g 15gm with applicator
Estradiol 25 μg 10 μg/ tablet
Vaginal ring 7.5 μg/24 h
Premarin 625 μg/g 42.5 g with applicator
Transdermal estradiol gel 1 mg/1 g
Nasal spray estradiol hemihydrate 150 μg/actuation
Will transdermal patches become the preferred option?
Discuss the controversies of HRT
The Women’s Health Initiative in 1990s-2001 released studies showing HRT caused health risks e.g. breast cancer/thrombosis/patient anxiety - however these studies were on older women who were 6-10 years on average past menopause, suggesting these health implications were pre-existing and there weren’t enough studies on early-onset menopausal women who were having HRT earlier on when experiencing symptoms
What may the benefits of HRT be?
Symptom relief Heart protection? Bone protection Cancer reduction Reduces Alzheimer’s? Patient request
Describe the 3 large studies to do with HRT
Three large studies
Heart and Estrogen/Progestin Replacement Study (HERS) (CCEPT in postmenopausal women with CHD)
Women’s Health Initiative (WHI) (healthy postmenopausal women)
Prospective, randomised, double-blind, placebo-controlled studies of continuous-combined estrogen progestin therapy (CCEPT)
Evaluated only one hormone combination; no perimenopausal women
HERS ended after 4.1 years
WHI was stopped at 5.2 years –increased risk of breast cancer
Million women study - retrospective
