Functional Gynaecology

Professor Clarke

● Centered around patterns of abnormal uterine bleeding and pelvic pain

Part 1: HPO Axis and Menstrual Cycle

● The ovary controls the menstrual cycle
● This in turn, is controlled centrally from the anterior pituitary gland and hypothalamus
● GnRH from the hypothalamus
→ stimulate anterior pituitary
→ release FSH and LH
● FSH: stimulate follicles
(developing eggs) within
the ovary - important for
reproduction
○ Follicles produce
oestrogen and
progesterone
○ These hormones
have an impact on
organs e.g. breasts,
uterus, brain,
endometrium,
vagina
● Follicles lined by granulosa
cells - produce oestrogen
● Theca cells develop
following LH surge -
produce testosterone and
progesterone
● Oestrogen = negative feedback effect centrally - keep hormone levels within control and
dictate menstrual cycle
● Testosterone peripherally converted to oestrogen by aromatase (produced by fat cells) -
additional oestrogen is produced in this manner
●
● Overweight women - more prone to heavy periods
○ More prone to endometrial cancer
○ Oestrogen driven (more fat cells)
Menstrual Cycle
● Ovulation - day 14
● Standard 28 day cycle - on average
● 21-35 days range
○ Related to length of PROLIFERATIVE PHASE - when endometrium is
proliferative (prior to ovulation)
● Luteal phase (post-ovulation) - constant → around 10-14 days
● Rising FSH → stimulate follicles to produce oestrogen (from granulosa cells)
○ Many follicles being developed

○ Oestro
gen levels rise → negative feedback to anterior pituitary → FSH levels drop
○ Most follicles will become atretic (STOP delevoping)
○ DOMINANT FOLLICLE – the one that is able to survive in low FSH environment
■ It can still produce oestrogen from granulosa cells despite drop in FSH
○ This higher level of oestrogen then becomes a POSITIVE FEEDBACK on
pituitary → further LH and FSH surge (near day 14)
○ Surge in LH → leads to ovulation

○ In IVF, LH used to make eggs ready for collection

EOSTROGEN IS PRODUCED THROUGHOUT CYCLE. PROGESTERONE IS NOT THE

SAME TREND

● No progesterone in proliferative stage of cycle

○ Subsequent to ovulation, progesterone levels rise and then SUDDENLY
plummets
■ Sudden withdrawal of progesterone → menstruation

○ Oestrogen dominated proliferative phase- causes lining of womb thickens

○ Subsequent to ovulation, endometrial lining becomes secretory (glandular and
ready for implantation of developing embryo)
 ● In most cycles → no embryo to implant and menstruation occurs due to sudden withdrawal of
progesterone

● After ovulation, empty follicle → corpus luteum (this produces progesterone from theca cells →
survive around 10 days on average – in absence of pregagncy, dies, progestrone production stops)

● HCG - developing trophoblast will produce HCG

○ Test this in pregnancy test
○ Similar in structure to LH
○ Maintains corpus luteum for 8 weeks or so, so corpus luteum continues to
produce oestrogen and progesterone for further weeks
■ This maintains early pregancy until placenta is large enough to take over
endocrine functions
○ Allows the placenta to develop more fully, and then the placenta will take over
these functions
○ HCG maintains corpus luteum and maintains production of progesterone → menstruation
does not occur

Menstruation
● As the progesterone withdrawal takes place, it leads to
spasm of underlying spiral arterioles
● Constriction and necrosis → shedding os superficial lining of
endometrium And bleeding from underlying spiral
arterioles
● Superficial lining of endometrium sheds each month
● Deeper basal layers are regenerative
○ Under influence of oestrogen, will continue to
proliferate

WHY ARE CYCLES IRREGULAR IF OVULATION DOES NOT

TAKE PLACE
EXPLAIN HOW THE COCP CAN REGULATE CYCLES AND
REDUCE BLEEDING
Natural cycle, eostrgen is produce all and progesterome
sometimes

Ovarian Activity
● At time of puberty: around 400,000 primary oocytes - females are born with all the
primary oocytes that they will ever possess
 ○ Only 400 will develop and mature to be released as an egg (ovulation to take
place)
● COCP - acts by preventing ovulation – therefore these women have fewer than 400
primary oocytes
○ Sperm produced in much greater quantities

● The first meiotic division will take place around ovulation

● The second meiotic division at the time of fertilisation

Menarche and Puberty

● Menarche - onset of menstruation
● Average age: 12-13
● Puberty is a process of sexual maturation

Menopause
● END of reproductive life
● Permanent cessation of menstruation
● Ovaries stop producing oestrogen and eggs
● Climacteric- transition from reproductive to non- reproductive phase of life
○

● Menopausal symptoms
○ Vasomotor symptoms- waves of hot flushes, disturbed sleep due to uncontrolled night
sweats → due to drop in oestrogen

STRAW reproductive ageing system

● Stages reproductive life
● Helps to determine what type of conditions will affect women in certain age categories
● Reproductive Stage
 ○ Pelvis pain, abnormal bleeding, fertility issues
● Menopausal Transition
○ Symptoms of oestrogen
deficiency e.g. vasomotor
symptoms, mood disturbance,
vaginal dryness
● Perimenopause
● Postmenopause
○ Loss of density, urinary
incontinence, prolapse,
development of gynaecological
malignancy

Delayed Menarche/Primary Amenorrhoea (beyond 16 years)

Can occur for a number of reasons:
● Imperforate hymen - structural
○ Blood unable to escape due to imperforate hymen - collection of blood and
distension of vagina (hematocolpos)
○ Associated with pain
● Vaginal agenesis - vagina may not develop
● Testicular feminisation/ androgen insensitivity
○ Phenotype XX, genotype XY

Delayed Puberty
Can occur through many reasons:
● Hypothalamic / pituitary failure
● Gonadal dysgenesis
● Turner’s Syndrome 45XO - underdeveloped ovaries, reduced production of hormones,
phenotypical features e.g. short stature, neck

Secondary Amenorrhoea
● In adult gynaecology this is more common
● Periods have started, but then stop for a duration of time
● Most commonly due to:
○ pregnancy/lactation
○ Hormonal contraception
○ PCOS
○ Primary ovarian insufficiency/premature menopause
○ Extreme changes weight - anorexia/obesity
○ Stress
○ Hypothyroidism
○ Iatrogenic - chemotherapy → induced ovarian failure
○ hypothalamic/pituitary tumour - prolactinoma (tumour of hypothalamus or pituitary
gland - increase in production of prolactin)
■ Visual disturbance - pressure from expanding mass in pituitary
 ■ Discharge from
nipples

Abnormal Uterine Bleeding (AUB)

● PALM COEIN Classification
● PALM - structural causes
● COEIN - non- structural causes

Abnormal Uterine Bleeding

● INCLUDES
○ Heavy menstrual bleeding (HMB)
○ Intermenstrual bleeding (IMB)
○ Post coital bleeding (PCB)
○ Postmenopausal bleeding (PMB)

Heavy Menstrual Bleeding

● Excessive menstrual blood loss which interferes with a women’s quality of life
○ Physical, social, emotional and/or material QoL
● Important to SOME degree to quantify amount of blood
● Lots of sanitary products, clots, bleeding through sanitary towel
● More important to know how this is impacting upon a woman’s life

Regular Cycle HMB

● Regular cycles = ovulation is taking place
● Not fully understood why periods are heavy
● When superficial lining is shed → glandular secretions
● But underlying blood vessels will bleed (normally stop bleeding through vasospasm and local
clotting mechanisms ) → problems with these mechanisms
○ Normally controlled by PGs, prostacyclins
○ Probably a local disorder in these mechanisms
○ Failure of spiral artery constriction

Irregular cycle HMB

● Usually underlying hormonal cause
● Absence of ovulation or less regular ovulation
● Lining of womb to proliferate and then bits of lining to shed at unscheduled times
○ Leads to erratic, unscheduled, heavy bleeding
● Treatment: often requires hormonal therapy or surgery
● More commonly seen at extremes of reproductive life (immature or perimenopause) → cycles
becoming less regular
○ In keeping with reduction of natural underlying fertility - ovulation is less regular
● Endometrial hyperplasia - absence of ovulation and release of progesterone, endometrium
allowed to proliferate more and more → hyperplasia
 ○  development of endometrial cancer over a number of years
■ Once menopause is reached, more often than not, this process reverses
● (Atypical hyperplasia - in addition to thickening, there are
cytologically abnormal/atypical cells )
○ More likely to go on and develop ovarian cancer (approx
40%)

Endometrial Polyps - from lining of women

● Outgrowths of endometrial tissue
● Usually benign
● Can be associated with IMB and subfertility

Fibroids - from underlying muscular layer (myometrium)

● Commonest benign tumour in women
● May have no symptoms at all
● Symptoms:
○ Pressure
○ Abdominal swelling
○ Pain uncommon
● Firm structures
● Interested in where the fibroids are situated
● ALWAYS arise from muscle layer
● Can remain within muscle itself - intramural
fibroids
● Can lead to uterus becoming enlarged
● Some can start to grow into the womb itself - or start
to distort it → submucosal fibroids (0,1,2
fibroids)
○ Often don’t lead to marked enlargement of uterus
○ Distorting the shape and stretching the endometrium - increased SA
○ Disruption to underlying menstrual mechanisms - particularly causative of heavy
menstrual bleeding
○ Fertility problems and subsequent miscarriage
● Subserosal fibroids - starting from lining of womb but growing outwards
● Intramural fibroids and the subserosal fibroids → will cause the uterus to become enlarged
○ Lead to heavy periods
○ And pressure symptoms
● Large fibroids can lead to pressure symptoms - pressure on bladder or bowel
● Women's uteruses should be the size of pear - should not feel on an abdominal
examination
● May become markedly enlarged with fibroids - can feel it abdominally
Complications of Fibroids
● Degenerative changes - most commonly seen in pregnancy
○ Women get older - fibroids can become calcified
○ Malignant changes - leomyosarcoma
○ Mostly seen in postmenopausal women
● Torsion of pedunculated fibroids (serosal)
○ On a narrow pedicle
○ Uncommon

Adenomyosis
● Deposits of endometrial tissue in myometrium (ectopic endometrium)
● Problems with dyspaenuia and heavy menstrual bleeding
● On USS - see evidence of deposits of endometrial
● Leads to uterine enlargement (tender and bulky uterus on abdominal palpation)
● Can be concurrent with endometriosis
Pelvic Pain

Primary Dysmenorrhoea
● Period pain
● Most common type - physiological
○ Pain arising from uterus from contraction of uterine muscle
○ Occurs cyclically
○ Classically: affected nulliparous women (teenagers)
○ Does not imply any pathology
○ Onset of pain may be prior to menstruation - classically will be relieved once
menstruation starts PID
○ Mechanism - PGs leading to myometrial contraction, uterine spasm and pain
● N+V, bowel disturbance

● Management: analgesia, NSAIDs, COCP (thin lining of womb leading to less uterine
contraction and less pain), mefenamic acid

Secondary Dysmenorrhea/Pelvic Pain

● Menstrual pain that does not become relieved by onset of menstrual flow- present
throughout and possibly beyond the menses

● Cyclical Causes:
○ Endometriosis
○ Adenomyosis
○ Mittelschmerz - ovulation pain (can lead to local peritonism due to blood and fluid being
release - 24-48 hours of pain) → mid cycle
● Non-cyclical Causes:
○ PID
○ Ovarian Cyst
○ Tubo-ovarian abscess
○ Rarely, fibroids (HMB and pressure symptoms)
○ IBS/Urinary Issues

Endometriosis
● 10% of women affected (1/10)
○ Most will NOT have problems with fertility
● Cyclical pain
● Can also present with deep dyspareunia
● Can have cyclical GI/urinary symptoms
● Endometrium (lining of womb) contains glands and stroma
○ Biopsies - look identical
○ Endometriosis = endometrium which is in the wrong place (ectopic)
● Most of endometrium is shed vaginally (period)
● Retrograde passage of menses and endometrial tissue = NORMAL
○ Can track back into fallopian tubes for example
○ HOWEVER, if this endometrial tissue survives → endometriosis
○ Despotis of endometrium: ovary, pouch of Douglas (deep endometriosis)
○ Most is superficial - not invading into bowel
 ○ Deep endometriosis can lead to
scarring and adhesions
■ Adhesions → block Fallopian
Tubes → subfertility
○ May be due to neovascularization
and impacts on local neurology
● In most women, examination will be
normal
○ Deeper endometriosis and
scarring - uterus and pelvic
organs may be more fixed, may
have a nodular appearance at the
top of the vagina
● Can have concurrent adenomyosis

● Gold standard investigation: Laparoscopy

- telescope put into abdominal cavity through small cut made in umbilicus
○ To diagnose - has significant risks
○ Can offer some surgical treatments
● First line Rx: analgesics or hormonal treatment

Other Forms of Endometriosis

● Deep infiltrating endometriosis → 1%
○ Pain/blood on urination/defecation
○ Vaginal/rectal nodules on examination
■ Referral to specialist centre may be required
■ Surgery - may required joint surgery with colorectal surgeries
■ Potential for complications
■ GnRH analogues - injections to induce a temporary menopause
● Useful in alleviating pains
● Impact on skeleton - loss of bone mineral density
● May need HRT to offset symptoms associated with lack of
oestrogen
○ THESE PATIENTS REQUIRED PRE-OPERATIVE MRI
AND 3/12 OF GNRH AND SURGERY BY
ENDOMETRIOSIS SPECIALIST SURGEONS
○ (GNRH ANALOGUES INDUCE TEMPORARY
MENOPAUSE TO RELIEVE PAIN n- oestorgen is given
alongisde this (HRT to alleivate vasomotor menpausal
symptons and prevent loss of bone density)

● Chocolate cyst (endometrioma)

○ Endometriosis deposits within ovary → cystic formation → old blood (hemosiderin)
○ Rx: surgical - cystectomy laparoscopically

Pre-menopausal Ovarian Cysts

● Often asymtpomatic but can cause non-cyclical pelvic pain.
● Most are physiological cysts (simple cysts). Often can resolve on their own if left
● SIMPLE/FUNCTIONAL
 ○ <5CM usually ignored as resolve over 2-3 cycles.
○ >5CM: US surveillance vs ovarian cystectomy (lap/abdominal)
■ If symptomatic or big - beyond 5cm, certainly beyond 8cm → generally better
removed
● Can rupture → peritonism
○ Can become ruppture (periotinsm) because hemorrhagic or torted (will lead to
necrosis, May require fallopian tube to be removed)

These complications are less frequent with the above, simple cysts
● More common with complex cysts (i.e solid, multilocular, bilateral)
○ Dermoid - heavier, more prone to twisting
○ Ovarian malignancies - women postmenopausally predominantly
■ Pain is not as common in ovarian malignancy

PID and Tubo-Ovarian Abscesses

● STI which ascends into the pelvis
○ Often gonorrhea or chlamydia - PRIMARY infection
○ Can get secondary opportunistic infections due to mucosal damage from chalmidia or
gonoroea
○ STIs → damage to fallopian tubes
■ Can lead to tubal blockage and subfertility
● In actute phase: Pain and fever and sepsis and vaginal discharge
● O/E- cervical excitation, inflammatory markers will be raised
● Can get subfertility and pain (adhesions)
● Rx: antibiotics
● USS - tubo-ovarian abscess? → surgical management
○ Late manifestation of untreated PID
○ Drainage usually performed surgically
● Remember contact tracing
● Required PID abx cef, doxy, met
Part 4 & 5: History and Examination
● Regularity of menstrual cycles
● Women’s fertility desires - present and future
○ Dictates potential treatment options
● Examination: bimanual pelvic examination

Investigations
Bedside
● HVS for MC+S
● Endocervical swab for NAAT
○ Often done for women presenting with pain and discharge
Bloods
● FBC for anaemia
○ HMB
○ Fibroids or severe clotting disorder → marked anaemia
● Clotting and TFTs if indicated - rare
○ Hypothyroidism → can be linked absent periods (but hyper does not cause heavy)
Imaging
● TA/TV US - main imaging modality in gynaecology
○ Transvaginal - higher frequency sound waves as vaginal probe is right next to the
pelvis, good images
○ Transabdominal - through a full bladder, view of uterus and ovaries
○ Less good with women of obesity or loaded bowels
● MRI - less frequently used; Main use is for 2 reasons
○ Map fibroids - size, number and site of fibroids when planning therapy
○ Deep endometriosis - allow us to see bowel involvement

Special Tests
● Hysteroscopy +/- endometrial biopsy for women at high risk of endometrial pathology
○ Small telescope inside uterus via vagina
○ OP service
○ Image inside of uterus and perform simple treatments e.g. removing small polyps
● Laparoscopy
○ Under anaesthetic
○ Under day case
○ Telescope through umbilicus
○ Can perform surgical procedures- dividing adhesions, removing cysts,
hysterectomy

● Abnormal bleeding - in general, benign pathology

● Women at high risk of endometrial pathology:

○ Intermenstrual bleeding - may imply problem with the cervix
○ Irregular bleeding
○ Infrequent heavy bleeding who are obese or have PCOS
■ Unopposed oestrogen, lack of progesterone → hyperplastic endometrium
○ Tamoxifen - in women who have had breast cancer
■ Partial agonist of oestrogen
■ Proliferative effect on oestrogen
○ Unsuccessful medical treatment
Outpatient Hysteroscopy
● Image uterus
● Thin Pipelle biopsy device

Treatment
● Conservative
○ Weight loss - particularly for women who have erratic and heavy bleeding due to
oestrogen excess (increased adipose)
● Medial
○ Non-hormonal (TXA, MFA)
○ Hormonal (Mirena, COCP, POP, injectable progestogens)
● Surgical
○ Minimally invasive/ uterine/fertility sparing
○ Radiologically

Non-Hormonal
● Tranexamic Acid
○ Antifibrinolytic drug - encourages clotting of underlying arterioles when superficial
lining is shed
○ Spiral arterioles will be clotted off reducing the amount of bleeding
○ Can reduce blood loss of about 50%
○ Benefit: non-hormonal (doesn’t interfere with pregnancy)
● Mefenamic Acid
○ NSAID
○ Treat pelvic pain
○ And to reduce blood loss to some degree

Hormonal
● Can be taken with the non-hormonal treatment
● Particularly effective for HMB

● Mirena
○ Small coil with a capsule in the middle - reservoir containing synthetic
progesterone
○ Released in tiny quantities per day (20mcg daily)
○ High concentration in womb - atrophic endometrium
○ May stop periods all together
○ Effective for menstrual pain
○ Suppress ectopic endometrium
■ In muscle layer - adenomyosis
■ In pelvis - endometriosis
○ Very effective contraceptive
○ Endometrial hyperplasia - caused by a relative lack of progesterone
■ Mirena can be very effective at thinning the endometrium
○ Reversible
○ Needs replacing every 5 years
● COCP
○ Good at regulating cycles
○ Reduce menstruation
 ○ Withdrawal of progesterone = menstruation
○ Take back to back with no periods at all: Higher dose of oestrogen, breakthrough
bleeding may be more common
● POP
○ Less effective contraceptive
○ If cannot take COCP: due to side effects, migraine, strong propensity to breast
cancer, smokers over 35, history of thrombosis, personally or in family
○ Rendering mucus of cervix unfavourable to sperm
○ Some can also prevent ovulation
■ Not licensed to used to treat menstrual iregulatires but can be used to
relieve HMB
● Injectable progestogens
○ Can be used unlicensed to treat menstrual problems
● GnRH analogues
○ Treatment of deep endometriosis
○ Suppress production of oestrogen - shrink fibroids (oestrogen dependent, render
endometriosis quiescent
○ Will induce oestrogen deficiency (menopause) → impact on skeleton
■ Not necessarily long term treatment
■ NOT first line
Esmya
● Selective progesterone modulator
● Withdrawn from market
● Inducing liver failure

Polypectomy
● Removal of polyp
● Can be OP or inpatient
● Biopsy - tissue sent for histopathology

Endometrial Ablation
● Device passed through cervix to uterus
● Heat is applied - strip away superficial lining of womb but also deeper basal layers where
regeneration takes place
● Menstruation does not occur (no regeneration)
○ Most women still do have some bleeding as parts of the womb are left untouched
but is much lighter
 ● Maintains uterus and considered minimally invasive → does take away lining of womb, only
indicated for women who do not require future fertility
● NOT CONTRACEPTIVE however - still need contraception after this technique

Hysterectomy
● Removal of womb
● Most effective treatment for heavy, painful bleeding
● Routes:
○ Key-hole approach - laparoscopically - should be first choice route
■ Minimally invasive
■ Can be day-case
○ Abdominal - if large uterus (fibroids or adenomyosis), or significant adhesions
present
■ Lower transverse incision
■ Midline incision for larger uteruses
■ Longer hospital stay
○ Vaginal - if significant prolapse present e.g. due to multiparity
■ No abdominal cuts
● Fallopian tubes removed
○ Source of ovarian cancer
○ No use anymore so just remove
● Generally leave ovaries in place - will continue to produce oestrogen
● Dependent on menopausal status and acceptability of HRT as oophorectomy will make
patient enter the menopausa
○ Women already perimenopausal (early 50s) or strong family history of ovarian cancers or
propensity to cysts → remove ovaries as well
■ Will require HRT to prevent menopausal symptoms

Management of Fibroids
These are Oestrogen dependent tumours of muscle wall in the womb
● Can be treated medically
● OR in form of hysterectomy
● Some want to retain uterus for future fertility
○ Myomectomy and UAE (uterine artery embolisation) - considered where fibroids
greater than 3cm in size as medical treatment may be less effective
■ UAE- cannula in femoral artery and angiogram, embolisation
○ AUE and myomectomy MAY PRESERVE FERTILITY
■ Blocks blood supply to uterus leading to ischaemic degeneration of
fibroids - performed under LA
● Angiogram
● Embolisation
● Impact of fertility is unknown
Myomectomy
● Fibroid being ‘enucleated’
● Have a good blood supply- risk of bleeding
Oncology
● Cervical screening
● Cervical cancer
● Endometrial cancer
● Ovarian cancer
● Vaginal/vulval cancer