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.

3.
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.

4.
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

5.
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

6.
 oral contraception;
 replacement therapy.
MAIN USES OF OESTROGEN

7.
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

8.
OESTROGEN FORMULATIONS
 Oral
 Transdermal patches, gels
 Subcutaneous implants
 Vaginal ( ring, cream, tablet or pessary )
 Nasal spray

9.
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.

10.
PROGESTERONE - Secretion
 By the ovary
 mainly the corpus luteum
 during the second half of the menstrual cycle.

11.
PROGESTERONE AND PROGESTINS
 Drugs which mimic the action of
 progesterone
 complement the action of estrogen on
primary and secondary sex characteristics

12.
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

13.
PROGESTINS
 norgestrel,
 levonorgestrel,
 norethindrone,
 norethindrone acetate,
 norethynodrel,
 ethynodiol diacetate,
 Desogestrel and norgestimate

14.
 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

15.
ABNORMAL UTERINE BLEEDING

16.
 Primary Dysfunctional uterine bleeding
(ovular)
Uterine fibroids
Uterine endometriosis(adenomyosis) – painful
periods
Secondary DUB
REGULAR, BUT HEAVY PERIODS

17.
 Primary Dysfunctional uterine bleeding –
 [anovular or ovular] – common
Uterine fibroids
Uterine endometriosis
Secondary DUB - caused by bleeding disorders {eg
ITP}
ABNORMAL UTERINE BLEEDING

18.
 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)

19.
 DUB
 Endometrial pathology
 Climacteric
 Fibroids/ adenomyosis
 Ovarian pathology
IRREGULAR AND BUT HEAVY PERIODS

20.
 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

21.
 Cervical ectropion
 Cervical polyp
 Cervicitis
 Cervical carcinoma
 Medical  appropriate antibiotics for infection ( based on C/S
reports )
VAGINAL BLEEDING AFTER INTERCOURSE

22.
long-term suppression of ovarian estrogen
production
(eg in endometriosis, uterine fibroids)
PROGESTINS

23.
AMENORRHOEA & MENOPAUSE

24.
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…

25.
 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

26.
 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

27.
JUST FOR JOKE

28.
 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

29.
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

30.
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

31.
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

32.
Modes of HRT
 Combination:
- Pills and patch
 Estrogen:
- Pills, patch, cream
 Progestins
- Pills, vaginal gels,
IUDs

33.
Patches vs. Pills
 Different routes of administration = different side
effects
 Pills 2 times likely to cause blood clots
than patches

34.
INCONTINENCE & PROLAPSE

35.
 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

36.
 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

37.
 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

38.
 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

39.
 Cystocele
 Uterine prolapse – primary, secondary, tertiary
 Rectocele
 Enterocele
I FEEL SOMETHING COMING DOWN

40.
NEOPLASIA

41.
 Infection or inflammation – vaginal discharge
 Dyskaryosis
 Malignancy – early sex, multiple partners, HPV, HSV-2
Infection, smoking, low socioeconomic status
CERVICAL SMEAR IS ABNORMAL

42.
 Pelvic mass ( ovary, fallopian tube, uterus)
 Ascites
 Bladder distension
 Bowel problems
DISTENDED ABDOMEN

43.
megestrol acetate:
 a progesterone derivative,
 used in treatment of endometrial cancer

44.
 Atrophic vaginitis
 Endometrial polyp, hyperplasia, cancer
 Cervical polyp, cancer
 DM, Obesity, HTN  risk factors for endometrial cancer
 tt - surgery
POSTMENOPAUSAL BLEEDING

45.
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

46.
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)

47.
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.

48.
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

49.
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

50.
DISCHARGE & PAIN

51.
 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…

52.
 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

53.
 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

54.
 Antibiotics based on C/S report
 O2, IV fluids, IV antibiotics septic shock
TREATMENT OF PID

55.
 Endometriosis
 Chronic PID
 Primary dysmenorrhoea
PAINFUL PERIODS & PAIN DURING
INTERCOURSE

56.
 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

57.
INFERTILITY

58.
Male causes – 25%
Anovular – 25%
Tubal blockade – 25%
Unknown – 25%
With Irregular periods  primary infertility
( PCOs, prolactinemia (anovulation))
 unexplained
CAUSES OF INFERTILITY

59.
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.

60.
ADVERSE EFFECTS
 Multiple pregnancy
 Ovarian carcinoma
 Hot flushes
 Headache

61.
FERTILITY CONTROL

62.
 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

63.
• 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

64.
• 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

65.
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

66.
 (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

67.
• pregnancy;
• undiagnosed vaginal bleeding;
• severe arterial disease;
• liver adenoma;
• porphyria.
PROGESTOGEN-ONLY CONTRACEPTIVE
ABSOLUTE CONTRAINDICATIONS

68.
 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

69.
Progestin Antagonists: Mifepristone
 Compete with the progestin receptors.
 Uses:
 Contraceptive.
 Abortifacient.

70.
Mifepristone (RU-486)
 effectiveness: is 95% effective during first 7 wks
following conception

71.
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

72.
 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

73.
 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

74.
 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

75.
 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

76.
 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

77.
 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

78.
 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 ?

79.
 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

80.
THANK YOU..