This interesting ppt deals with pharmacological aspects of Gynecology highlighting various aspects of it...it'll be very useful for the beginners in Gynecology...

1. Dr. V.SATHYANARAYANAN M.D
PROFESSOR OF PHARMACOLOGY
SRM MCH & RC
CHENNAI, INDIA
DRUG THERAPY 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.

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.

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

10.  oral contraception;
 replacement therapy.
MAIN USES OF OESTROGEN

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

12. OESTROGEN FORMULATIONS
 Oral
 Transdermal patches, gels
 Subcutaneous implants
 Vaginal ( ring, cream, tablet or pessary )
 Nasal spray

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

19. PROGESTINS
 norgestrel,
 levonorgestrel,
 norethindrone,
 norethindrone acetate,
 norethynodrel,
 ethynodiol diacetate,
 Desogestrel and norgestimate

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

22. ABNORMAL UTERINE BLEEDING

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

32. AMENORRHOEA & MENOPAUSE

33. Find out the cause
(secondary amenorrhoea –
 pregnancy
 stress
 PCOS ( infertility & oligomenorrhoea)
 Hyperprolactinemia – prolactinoma ( headache &
visual disturbances)
 Hypo/hyperthyroidism
 premature menopause(associated with hot flushes &
night sweats)
 Drugs – phenothiazines, progestogens
INFREQUENT PERIODS, NOT HAD ANY
FOR 7 MONTHS…

34.  PCOS  combined OCP (patient wishes for regular
periods )
 induce ovulation ( wishes pregnancy)
surgery (ovarian drilling)
 Menopause  combined OCP
 combined HRT
 Hyperprolactinaemia  dopamine agonists
 ( bromocriptine, cabergoline)

TREATMENT OPTIONS

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

36. JUST FOR JOKE

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

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

42. Modes of HRT
 Combination:
- Pills and patch
 Estrogen:
- Pills, patch, cream
 Progestins
- Pills, vaginal gels,
IUDs

43. Patches vs. Pills
 Different routes of administration = different side
effects
 Pills 2 times likely to cause blood clots
than patches

44. INCONTINENCE & PROLAPSE

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

50. NEOPLASIA

51.  Infection or inflammation – vaginal discharge
 Dyskaryosis
 Malignancy – early sex, multiple partners, HPV, HSV-2
Infection, smoking, low socioeconomic status
CERVICAL SMEAR IS ABNORMAL

52.  Pelvic mass ( ovary, fallopian tube, uterus)
 Ascites
 Bladder distension
 Bowel problems
DISTENDED ABDOMEN

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

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)

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.

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

67. DISCHARGE & PAIN

68.  Infection – candida, trichomanas vaginitis, etc
 Inflammation
 Foreign body
 Candida – ass with itching, OCP, antibiotics, DM
 thick white discharge,
 premenstrual,
 intense itching worsening at night
 TV – grey frothy discharge, pain, dyspareunia, burning
 Bacterial vaginosis  green discharge
 Gonococci, chlamydia  yellow mucopurulent, postmenstrual,
pain, burning ( gono)
I HAVE CONSTANT IRRITATING VAGINAL
DISCHARGE…

69.  Advice on Personal hygiene and clothing
 Candida - clotrimazole cream, oral fluconazole
 trichomanas vaginitis - metronidazole
 Bacterial vaginosis - metronidazole
 Gonococci – penicillins + probenecid or erythromycin
 chlamydia – doxycycline
 Herpes – acyclovir
 Treat the partner simultaneously
TREATMENT

70.  Acute PID – fever, pelvic pain, foul smelling vaginal discharge
 STI or STDs
 IUCD
 Secondary PID
 ACUTE ABDOMEN –
 ectopic pregnancy,
 ovarian cyst,
 Related to bowel problems
I AM UNWELL AND HAVE ABDOMINAL
PAIN & DISCHARGE

71.  Antibiotics based on C/S report
 O2, IV fluids, IV antibiotics septic shock
TREATMENT OF PID

72.  Endometriosis
 Chronic PID
 Primary dysmenorrhoea
PAINFUL PERIODS & PAIN DURING
INTERCOURSE

73.  AIM 
 relief of pain
 To induce amenorrhoea
 NSAIDs
 COC pills for 6 months then till pregnancy is desired
 Progestogens – oral, injectable, IUD
 Danazol
 GnRH agonists
TREATMENT

75. INFERTILITY

77. Male causes – 25%
Anovular – 25%
Tubal blockade – 25%
Unknown – 25%
With Irregular periods  primary infertility
( PCOs, prolactinemia (anovulation))
 unexplained
CAUSES OF INFERTILITY

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.

81. ADVERSE EFFECTS
 Multiple pregnancy
 Ovarian carcinoma
 Hot flushes
 Headache

84. FERTILITY CONTROL

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

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

101. • pregnancy;
• thrombo-embolism;
• multiple risk factors for arterial disease;
• ischaemic heart disease;
• severe hypertension;
• otosclerosis;
• breast or genital carcinoma;
• undiagnosed vaginal bleeding;
• breast-feeding;
• porphyria.
COMBINED ORAL CONTRACEPTIVE (COC) – ABSOLUTE
CONTRAINDICATIONS

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

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

111. • pregnancy;
• undiagnosed vaginal bleeding;
• severe arterial disease;
• liver adenoma;
• porphyria.
PROGESTOGEN-ONLY CONTRACEPTIVE
ABSOLUTE CONTRAINDICATIONS

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

113. Progestin Antagonists: Mifepristone
 Compete with the progestin receptors.
 Uses:
 Contraceptive.
 Abortifacient.

115. Mifepristone (RU-486)
 effectiveness: is 95% effective during first 7 wks
following conception

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

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

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

133. THANK YOU..