This interesting ppt deals with pharmacological aspects of Gynecology highlighting various aspects of it...it'll be very useful for the beginners in Gynecology...
2. SEX AND HORMONES
The sex hormones are a special kind of
steroids,
released mostly by the gonads
and to a lesser degree by the adrenal glands.
affect the brain, genital and other organs
Two types
1. Androgens
2. Estrogens
Both sexes have both hormones.
3.
4.
5. ESTROGENS AND PROGESTINS
Estrogens include estradiol and others
and are referred to as “female hormones”
because women have higher levels.
Progesterone is a type of hormone that
prepares the uterus
for the implantation of a fertilized ovum
and promotes the maintenance of pregnancy.
6.
7.
8. STEROIDS BASICS
Steroid hormones are all derived from cholesterol
Cholesterol contains cyclopentanophenanthrene
ring
Estrogen and progestins are just two
of the many steroids found in the human body
Mechanism: - Modulate gene expression inside
cell
Cholesterol
9. Actions of estrogens
Development and maintenance of internal
(fallopian tubes, uterus, vagina), and external
genitalia
skin: increase in vascularization,
development of soft, textured and smooth skin
bone: increase osteoblastic activity,
decreases resorption
electrolytes: retention of Na+, Cl- and water by
the kidney
cholesterol: Increases HDL, decrease LDL
Enhance coagulability of blood
11. Oral contraception;
• the treatment of symptoms of menopause;
• the prevention of osteoporosis•
the treatment of vaginal atrophy;
• the treatment of hypo-oestrogenism (as a result of
hypogonadism, castration or primary ovarian failure);
• treatment of primary amenorrhoea;
• treatment of dysmenorrhoea;
• treatment of oligomenorrhoea;
• treatment of certain neoplastic diseases;
• treatment of hereditary haemorrhagic telangiectasia
(Osler–Weber–Rendu syndrome);
• palliative treatment of prostate canceR
USES OF
OESTROGENS
15. Progestins - Physiological Effects:
Development of the endometrium.
Development of the mammary gland during
pregnancy.
Milk secretion starts when its level decrease with
birth.
Thermogenic action.
16. PROGESTERONE - Secretion
By the ovary
mainly the corpus luteum
during the second half of the menstrual cycle.
17. PROGESTERONE AND PROGESTINS
Drugs which mimic the action of
progesterone
complement the action of estrogen on
primary and secondary sex characteristics
18. to control anovulatory bleeding;
to prepare the uterine lining in infertility
therapy and
to support early pregnancy;
for recurrent pregnancy loss due to
inadequate progesterone production;
in the treatment of intersex disorders,
to promote breast development.
USES OF PROGESTERONE
20. as part of the combined oral contraceptive
and in the progestogen-only pill.
Medroxyprogesterone acetate administered by depot
injection is used when parenteral contraception is indicated.
as an anti-androgen in prostate cancer, e.g. cyproterone
acetate;
as part of hormone replacement therapy
endometriosis;
in menstrual disorders, such as premenstrual tension,
dysmenorrhoea and
menorrhagia;
USES OF PROGESTOGENS
23. Primary Dysfunctional uterine bleeding
(ovular)
Uterine fibroids
Uterine endometriosis(adenomyosis) – painful
periods
Secondary DUB
REGULAR, BUT HEAVY PERIODS
24. Primary Dysfunctional uterine bleeding –
[anovular or ovular] – common
Uterine fibroids
Uterine endometriosis
Secondary DUB - caused by bleeding disorders {eg
ITP}
ABNORMAL UTERINE BLEEDING
25. Tt of choice Trenexamic acid during menses ( reduce
bleeding 50%)
Associated pain mefenamic acid
Combined oral contraceptive pill
Levonorgestrel IUCD ( warn of irregular menstrual cycle upto
9 months)
Danazol ( but ADR like acne, weight gain, voice changes)
Iron supplements
Progestogens are not indicated
SURGICAL Tt endometrial ablation,
hysterectomy(definitive)
TREATMENT OF PRIMARY DUB
(DYSFUNCTIONAL UTERINE BLEEDING)
26. DUB
Endometrial pathology
Climacteric
Fibroids/ adenomyosis
Ovarian pathology
IRREGULAR AND BUT HEAVY PERIODS
27. anemia iron supplements
In the climacteric combined HRT
high doses of progestogens in the second half of
menstrual cycle
With anovular DUB resulted in endometrial
hyperplasia progestogens in high doses
Consider Levonorgestrel IUCD release continuous
progestogens locally for upto 5 years
SURGICAL Hysterectomy is definitive
TREATMENT OF HEAVY IRREGULAR
PERIODS
28. Cervical ectropion
Cervical polyp
Cervicitis
Cervical carcinoma
Medical appropriate antibiotics for infection ( based on C/S
reports )
VAGINAL BLEEDING AFTER INTERCOURSE
29. long-term suppression of ovarian estrogen
production
(eg in endometriosis, uterine fibroids)
PROGESTINS
35. Premenstrual syndrome – around 35 yrs, resolved by menses,
during the week before menses, tension, aggression,
depression
Secondary Dysmenorrhoea –
endometriosis ( adenomyosis ) – heavy periods
PID
Pelvic venous congestion
INTOLERABLE MENSTRUAL PERIODS
37. Supportive –reassurance cognitive and relaxation therapy
Medical-
COC
Evening primrose oil
Vitamin B6
SSRIs
High dose estrogens + progestins
GnRH agonists to stop ovarian function temporarily
TREATMENT FOR PMS
38. Menopause
Transition period in a woman's life when
her ovaries stop producing eggs,
her body produces less estrogen and progesterone,
and menstruation becomes less frequent
Symptoms are
mood swings,
hot flashes and
vaginal dryness
39. Combined estrogens and progestins
Currently very popular forms for HRT
combine an estrogen (natural or semi-synthetic) with
an orally effective progestin
Prempro and Premphase
FemHRT
Combipatch
40.
41. Hormone Replacement Therapy
(HRT)
Estrogen + progestins or either!
Medical treatment for menopausal or post-menopausal
women
Progestins keep weight off and stop cell proliferation
Benefits of estrogen:
Reduction in loss of bone mass (osteoporosis)
Decreased risk of cardiovascular disease
Positive effect on cognitive function
45. PRE-TREATMENT – BP measurement,
Weight,
breast examination,
cervical smear,
pelvic examination
6 monthly – Wt,
BP
Yearly – breast examination
3-yearly – mammography, cervical smear
SCREENING PROGRAM FOR HRT
46. Short-term HRT for menopausal symptoms – beneficial,
outweigh risks
Decision for HRT – individual
Lowest dose, shortest period, review annually
Inc risk of fractures, > 50 use HRT only when other
therapies C/I
Healthy woman without menopausal symptoms – advised
against HRT
NO BENEFITS for CHD, cognition
C/I past H/O breast cancer
Oestrogen alone woman without uterus
HRT ADVICE FOR PRESCRIBERS
47. Sphincter incontinence ( GSI ) – multiparity, prolonged labour,
H/O uterovaginal prolapse
Urodynamics normal
Detrusor instability – urgency, urge incontinence
Mixed incontinence
Tt- pelvic floor exercises + physiotherapy
Drugs alpha agonists ( phenylproponalamine)
surgery
EVERY TIME I COUGH, I LEAK URINE
48. Detrusor instability
GSI
Mixed incontinence
Neurological disorder ( uncommon )
Detrusor instability
H/O urgency, frequency, nocturia with or without UTI
Tt – alter fluid intake habits,
Anticholinergic drugs flavoxate, oxybutinin detrusor
relaxation ( S/E – dry mouth. Constipation, blurring of vision)
No surgery
I HAVE TO RUSH TO THE TOILET,
OTHERWISE I LEAK URINE
49. Cystocele
Uterine prolapse – primary, secondary, tertiary
Rectocele
Enterocele
I FEEL SOMETHING COMING DOWN
55. megestrol acetate:
a progesterone derivative,
used in treatment of endometrial cancer
56. Atrophic vaginitis
Endometrial polyp, hyperplasia, cancer
Cervical polyp, cancer
DM, Obesity, HTN risk factors for endometrial cancer
tt - surgery
POSTMENOPAUSAL BLEEDING
57.
58. SERMs
Selective Estrogen Receptor Modulators
Because Estrogen receptors differ slightly
in different organs,
SERMs can target receptors of a certain organ
So a SERM that blocks estrogen’s effects in
breast cells won’t impact
estrogen binding in the uterus!
Tamoxifen
59. Uses of SERMs..
Used before or after menopause
Can help in slowing metastasis of cancer breast
Can treat osteoporosis
Advantage: specificity
Yet to find a SERM that has no negative side effect (
both mentioned cause colon cancer)
60.
61. Tamoxifen
Non streoidal competetive estrogen antagonist
Partial-agonist antagonist in breast cancer, hypothalamus,
anterior pituitary;
agonist in endometrium, bone, and liver.
Effective orally
palliative or adjuvant treatment for ER + metastatic (
hormone dependent) breast cancer.
Use for longer than five years = 3-5x ↑risk of endometrial
cancer,
S/E : Amenorrhoea, hot flushes, N, V, Bleeding
also may increase risk venous thrombosis and cataracts.
62.
63. ANTIESTROGENS - SERD
Fulvestrant
Antagonist at all tissues with estrogen receptors
250 mg I.M depot injection, once a month
Uses breast cancer resistant to tamoxifen
Side effects headache, hot flushes, nausea
64. AROMATASE INHIBITORS
Aromatase catalyses the final step
In estrogen synthesis
Letrozole, anostrozole, vorozole, fadrozole
Not steroids
Reversible inhibition
Preferred drugs in breast cancer
No risk of thromboembolism or endometrial cancer
78. Clomiphene citrate
: is a partial agonist of estrogen
(so binds receptors
but doesn’t act as a full agonist,
thus get less activity),
hypothalamus therefore thinks
there’s not enough estrogen around →
↑FSH/LH →stimulate follicle
and induce ovulation.
Give clomiphene 50 mg daily ( day 2-6 ) for 5 days to get
follicle stimulation
Ovarian hyper stimulation may occur.
89. Nearly 50% of all women in their twenties in the UK
use this form of contraception.
It is the most consistently effective contraceptive
method
and allows sexual relations to proceed without
interruption
but it lacks the advantage of protection against
sexually transmitted disease that is afforded by
condoms.
The most commonly used oestrogen is
ethinylestradiol.
THE COMBINED ORAL CONTRACEPTIVE
90.
91. • thrombo-embolic disease;
• increased blood pressure;
• jaundice;
• migraine – precipitates attacks or aggravates
previously existing migraine;
• increased incidence of gallstones;
• associated with increased risk of liver cancer.
COMBINED ORAL CONTRACEPTION (COC)
– ADVERSE EFFECTS
105. Levonorgestrel 1.5 mg
as a single dose as soon as possible,
preferably within 12 hours of,
and no later than 72 hours
after, unprotected sexual intercourse.
POST-COITAL CONTRACEPTION
106.
107.
108.
109. (e.g. norethisterone, norgestrel)
are associated with a high incidence of menstrual
disturbances, but are useful if oestrogen-containing pills are
poorly tolerated or contraindicated
(e.g. in women with risk factors for vascular disease such as older
smokers, diabetics or those with valvular heart disease or migraine)
or during breast-feeding.
Contraceptive effectiveness is less than with the combined pill,
as ovulation is suppressed in only
approximately 40% of women and
the major contraceptive effect is on the cervical mucus
and endometrium.
PROGESTOGEN-ONLY CONTRACEPTIVE
PILLS
112. are more effective than oral preparations.
A single intramuscular injection of medroxy
progesterone acetate provides contraception for ten
weeks
with a failure rate of 0.25 per 100 women per year.
It is mainly used as a temporary method
(e.g. while waiting for vasectomy to become effective),
but is occasionally indicated for long-term use in women for
whom other methods are unacceptable.
The side effects are essentially similar
After two years of treatment up to 40% of women develop
amenorrhoea and infertility,
so that pregnancy is unlikely for 9–12 months after the last
injection
DEPOT PROGESTOGEN INJECTIONS
117. A 26-year-old woman consults you in your GP
regarding advice about starting the combined
oral contraceptive pill.
Question
Outline your management of this patient.
CASE HISTORY
118. It is very important to take a careful history
in order to exclude any risk factors
which would contraindicate the combined oral contraceptive,
such as
a past history of thrombo-embolic disease
or risk factors for thrombo-embolic disease.
In addition, it is important to ascertain whether
the patient is a smoker and
when she last had a cervical smear.
It is important to exclude
a history of migraine and
to check her blood pressure.
ANSWER
119. The combined oral contraceptive is probably an appropriate
form of contraception in a woman of this age,
who would possibly be highly fertile,
as it is the most reliable form of contraception available,
provided that there are no risk factors to contraindicate the
combined oral contraceptive
There are many COCs on the market and
selection for this individual would be
dependent on
a balance of achieving good cycle
CHOICE OF OCP FOR THIS PATIENT
120.
121. control and weighing
the beneficial effects on plasma lipids offered by
the newer progestogens, such as
desogestrel, gestadine and norgestimate,
against the recently reported
two-fold increased risk of venous thrombo-embolism
noted with desogestrel and gestadine.
In a woman of this age, the beneficial effects on plasma
lipids are probably of minor importance and
in view of the increased risk of venous thrombo-embolism
it would probably be appropriate to choose a pill containing
norethisterone, levonorgestrel or norgestimate.
CHOICE OF PROGESTIN FOR THIS
PATIENT
122. The majority of women achieve good cycle control
with combined oral contraceptives
containing oestrogen at a dose of
about 30–35 μg;
pills containing the higher dose of oestrogen
would only be required
if the individual was on
long-term enzyme-inducing therapy
(e.g. rifampicin) or anticonvulsant medication.
THE DOSE OF ESTROGEN FOR THIS
PATIENT
123.
124.
125. A 50-year-old woman consults you about her
symptoms of flushing and vaginal discomfort.
She is thin and is a smoker.
Question
Outline the therapy most likely to be of benefit,
including the reasons for this.
CASE HISTORY 3
126. This woman is probably menopausal
and is suffering the consequences of
the vasomotor effects of the menopause,
as well as vaginal dryness.
The vaginal dryness could be treated
locally with short periods of treatment with
topical oestrogens.
ANSWER
127. However, in view of her other symptoms,
a better option would be to start her
on hormone replacement therapy.
If she still has an intact uterus then
it is important to give
both oestrogen and cyclical progestogen
to protect the endometrium from hyperplasia.
Depending on preference, life-style and
the likelihood of compliance,
either oral therapy or
patches may be appropriate.
WHY HRT ?
128. In this woman,
who has risk factors for osteoporosis,
such as smoking and thinness,
it may be of benefit to continue the hormone
replacement Therapy
for a period of at least five years
and possibly longer,
although it is important to exercise caution
with regard to her risk for breast cancer
and cardiovascular disease
DURATION OF HRT IN THIS WOMAN