The Menstrual Cycle Flashcards
What is the endometrium of the uterus?
The inner lining of the uterus that is shed every month during the menstrual cycyle
-Glandular tissue, under endoncrine control
- Extensive stroma
- Highly vasculurised networked supploed by spiral arteries
- Distinct histological changes with phases of the m cycle (Noyes criteria)
- Columnar epithelial cell lining (proliferates and degenerates in one cycle)
- Glands extend deep into the endometrial stroma
- Implantation occurs 6-12 days after fertilisation
- Window of implantation - endometrium optimally receptive to blastocyst (36hrs).
What comprises the Upper Female Reproductive Tract (FRT)
- The fallopian tubes
- ovarian ligament
- Fimbriae
- UTERUS
- Ovary (perimetrium, myometrium and endometrium)
What is the Lower FRT comprised of?
The cervix and vagina
What is the female repoductive lifecycle?
- Menarche:
- first ovarian-controlled uterine bleed
- Maturation of HPO axis
- increase in oestrogen (Sexual characteristics)
- Childbearing years (mestrual cycle)
- Around 28 day cycle
- menses, menstruatuion (bleeding phase)
- Menopause/Climacteric
- Oestrogen withdrawl, follicle depletion
- Cessation of menses
- Size, function of ovaries
- Mean age 51.4
What is the differnece between the ovarian and uterine cycle?
- Ovarian : interval between successive ovulations
- describes ovum maturation and release under endocrine regulation
- Progression of follicle - corpus luteum
- Uterine cycle:
- comprises the follicular pase (1-14 days) and the luteal phase (15-28 days)
- Folliculogenesis
- Uterine cycle - describes the effects of oestrogen and progesterone on the uterus (endometrium)
- Has a proliferative and secretory phase
- Has vascular funcrtion, menses
- Angiogenesis
What are the main reproductive hormones in the FRT?
Oestradiol-17ß
* produced from androstenedione and aromatase in granulosa, CL and adipose
**Progesterone (P4) **
* secreted by corpus luteum
**Follicle Stimulating Hormone (FSH) **
* follicle development and recruitment
**Luteinising Hormone (LH) **
* maturation of dominant follicle, ovulation, maintenance of the CL
**Inhibins **
* produced by ovarian granulosa cells to inhibit FSH secretion; Inhibin A during luteal
phase; Inhibin B in follicular phase
Anti-Mullerian Hormone (AMH)
* marker of ovarian reserve
What is the action of oestrogen (c18 steroid)?
- Widespread effects on reproductive, musculoskeleta,vascular and cns
- Regulate GnRH secretion
- stimulate proliferation of endometrium
- Prepares endomentrium for progesterone action
- -Stimulate sex characteristics of female
- Stimulates ductal growth of breast tissue.
What is the action of Progesterone (c21 steroid)?
- Pro gestation - hormone of pregnancy
- Regulate GnRH secretion
- Prepare endometrium for implantation
- Stimulate decidualisation of the endometrium
- Maintain the uterus during pregnancy
- Stimulate growth (alveolar) of breast tissue
- Synergistic and opposing effects to oestrogen
What is the idealised menstrual cycle?
- Day 1-7 bleeding
- Proliferative (Follicular) - when bleeding is more or less over - endometrium begins to regenerate
- Day 12-14 Ovulation
- Secretory (Luteal) phase (!4-28)
- Implantation- this cycle stops if pregnancy occurs
What is dysmenorrhoea?
- painful periods
What are the proliferative and secretory phase dominated by?
Proliferative - oestrogen - dominated
- variable duration typically 14 days
Secretory - progesterone dominated
Important so that women know when they are most fertile
Why do FSH and LH begin to increase at the start of the menstrual cycle?
- act on the follicles of the ovary which secrete eostrogen
- these promote endometrial proliferation
- Around Day 14 - there is a LH peak which is needed for oestrogen levels to rise prior to ovulation = positive feedback regulation
- After ovulation LH levels decrease rapidly
- Progesterone levels increase so that endometrium can thicken so that a blastocyst can embed (prepares endometrium for implantation)
- If no implantation, progesterone levels, and oestrogen levels fall off and LH and FSH levels begin to rise again
What process do inhibins inhibit in the menstrual cycle?
- The recruitment of follicles
- Once there are enough follicles the growth of other follicles are supressed
stalks
What are pinopodes?
- Markers of endometrial receptivity that grow on the endometrial cell layer
- Attract the blastocyst to them
What is the difference between proliferative and secretory ohase endometrium?
- Prolferative : round,regular. Stroma- supprt,nutrients
- Secretory - tortuous,twisted glands .Glycogen droplets prepares for conception - first nutrition for embryo
What supplies the endometrial vascular supply?
- The uterine artery and vein
What layer of the endometrium sheds?
- The functional layer of the endometrium
What is the vascular aspect of the endometrium?
- Rapid angiogenesis and spinal artery lengthening in ptoliferative phase
- Endometrial regression, spinal arteru coiling causes resistance to blood flow resulting in endometrial hypoxia followed by tissue degeneration
- Matrix metalloproteinases (MMP-8-9) from endometrial stroma and proteases from invading leukocytes during late secretory phase begin matrix degradation
- Mechanism : Progesterone withdrawl increases expression of COX 2 and increased prostaglandin (PGF2a) production by endometrial stromal cells and increased prostaglandin-receptor density on blood vessels = vasoconstriction
- (primary symenorrhea caused by PGCS inducinf myometrial contractions and ischaemia)
- Matrix metalloproteinases (MMPs) from endometrial stroma and proteases from invading leukpcytes during late secretory phase begin matix degradation and recovery
- Mestrual blood consists of endometrial cells, unfertilised ovum
- Low viscocity blood and lack prothrombin, thrombin and fibrinogen that prevnt clotting - needs to leave the endometrium
What happens during Day 1-7 proliferative/follicular phase?
Days 1-7 - P4 and E2 levels are low
- Endometrium shed then regrows; mestruation
- Increased GnRH secretion from the hypothalamus
- P4 and E2 decrease due to CL demise - Increased levels of FSH (-ve feedback from steroids)
- FSH act on ovarian follicular cells to increase E2 production
- Of several competing follicles , a single dominant follicle is selected. Other recruited follicles under atresia
- Endometrial glands mostly straight with evidence of mitosis
What happens during days 8-14 of the proliferative/follicular phase?
- Dominant follicle matures with the signifcant increase in size - secretes more E2 from increasing number of granulosa cells - endometrial proliferation and thickening
- High E2 circulatinf levels exceed a certain threshold, switching to +ve feedback on LH production from anterior pituitary
- LH surge induced; induced ~ 24-36 h later, follicle rupture - oocyte release - ovulation
- ## Ovum picked up by fimbriae of fallopian tube and enters oviduct
What is the luteal/secretory phase (days 14-28)?
- Under influence of LH, Empty follicle converted into CL- secretes mostly P4 but also E2
- P4 causes differentiation of endometrial glands to prepare for implantation
- P4 maintains endometrium ; induces decidualisation
- High P4 levels suppress LH and FSH release
- Oocyte remains in oviduct
- If no no fertilisation, CK degenerates - reduced P4
- Vasoconstriction via prostaglandinds (pgS); ischaemia; no vascular support for endometrium, meneses
- Low P4/E2 lebels- GnRH brake release. FSH and cycle begins again
What is decidualisation?
- The transformation of endometrial stromal cells cells to decidual cells by cAMP, progesterone
- Secretory, glycogen-rich, lipid0rich cells
- Early nutrition for embryo
- Secrete prolactin (anterior pituitary)
- Decidua rich in uterine NK cells
- Plays a role in immune tolerance
- Impaired decidualisation implicated in miscarriage, endometriosis
What effect does the mesntrual cycle have on cervical mucus?
- In proliferative phase
- under E2 influence, mucus is thin, watery, stretch to aid sperm transport
- Secretory phase
- Thick impenetrable mucus
- Basis of contraception
What are some menstrual disorders?
- Paindul period/cramps - dysmenorrhoea
- Primary - absence of underlying pelvic pathology
- Secondary - underlying pelvic pathology
- Ovulation pain - Mittelschmerz (‘middle pain’)
- swelling/stretching or ripture od follicle on ovary; bleed
- PMS
- Fluctuating hormone levels - mood swings, irritability, fatigue
- affects 75% of women at some point in their lives
- Absence/ Heavy/ irregular periods
What is endomentriosis?
- When endometrial tissue is found elswehere in the body/ outside of the uterus (e.g. ovaries f tubes, pelvic, periotoneum etc)
- 10% global incidence in women pre-menopause
- 6-7 year delay in diagnosis
- Cause of infertility; adhesions may cause bowel obstructions
- Bladder involvement may cause dysuria
- Explants remain responsive to hormonal stimiulation
- Causes retrogde menstruation
- Inflammation , cytokines
- Reduced apoptosis/stem cells
- Angiogenesis/dossenmination through lymphatics
- What are leiomyamas (fibroids)?
- Derived from the uterine smooth muscle (myometrium)
- Hormone dependent - can enlarge and regress after menopause
- Most common benign tumout in females ; no progression to cancer
- Frequently manifests with menorrhagia, sometimes w metrorrhagia
- often asymptomatic but sometimes vary
- Associated with the presence of a mass (back pelvic pain or pressure), bloating, constipayed, urinary frequency, dyspaureunia
- Pregnancy and infertility - can prevent blastocyst attatchement to the uterine wall
- May block the fallopian tubes
- Can lead to difficulties during labour may need c section
What are the different types of fibroids?
- Pedomculated submucosal fibroid
- Intramural
- Submucosal
- Subserosal
- Pedonculated
What are types of hypothalamic dysfunction (HPO )?
- disordered gnrh released caused by:
- stress
- strenous exercise
- excessive weight gain/loss
- eating disorders
- Jet lag
- Pulsatile GnRH release disrupted
- Ovulation affected
- Altered sex steroids levels in circulation (E2 in blood)
- Prolactinaemia, hyper/hypothyroidism, Cushing;s (amenorrhoea, anovulation)
