female sex hormones. powerpoint presentation

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1. Female sex hormones:
Oestrogens

2. Cholesterol
Pregnenolone
Progesterone
17-α- Hydroxy
pregnenolone
17- Hydroxy
progesterone
Dehydro-epi
androsterone
Andro-
stenedione
Oestrone
Oestriol
TESTOSTERONE
OESTRADIOL
Premenopausal : ovaries (10-100 µg)
Postmenopasual :adipose tissue(2-10 µg)
Pregnancy : placenta (up to 30mg)

3. LH FSH
Progesterone
Oestrogen

4. http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/Female04/cycle.jpg

5. Oestrogens
Natural
Oestradiol
Oestrone
Oestriol
Synthetic
1.Steroidal
• Ethinyl oestradiol
• Mestranol
• Tibolone
2.Non-steroidal
•Diethylstilbesterol
• Hexestrol
• Dienestrol

6. Pharmacokinetics
•Absorption:
•Well absorbed by oral, parenteral & transdermal admn.
•Oestradiol undergoes high first pass metabolism.
Therefore other synthetic preparations are more
commonly used.
•Oestradiol esters i.m. admn. Slowly absorbed &
prolonged action
•Transport: highly protein bound (SSBG,albumin)
•Metabolism:
– by liver enzymes
–Significant entero-hepatic circulation
–excretion by urine after conjugation

7. Oestrogen preparations
Oral
•Conjugated oestrogen
(0.625, 1.25 mg tab., 25 mg inj)
•Ethinyl oestradiol(0.01, 0.5,0.1mg)
•Mestranol (0.1 mg tab)
•Oesradiol succinate (1, 2 mg tab.)
intramuscular
•Oestradiol benzoate (5, 10 mg
inj.)
Intravenous
•Fosfestrol tetrasodium
(60 mg/ml inj, 120 mg tab)
Topical
•Dienestrol 0.01% vaginal cream
Transdermal
•Oestradiol (25,50 or 100 mcg/24 h)
•Oestradiol + norethisterone
(50 mcg + 0.25mg)

8. Oestrogens: Actions
Sex organs:
vagina, uterus & fallopian tubes (pubertal changes)
Vaginal epi. Thickened,stratified & cornification
endometrium: proliferative & secretary phase
Menstruation (anovulatory cycles)
cervical secretion – watery alk. secrn
Secondary sexual characteristics:
Growth of breast
facial, pubic & axillary hairs, feminine body contour

9. Metabolic Effects
•Anabolic effect (weak)
•Fusion of epiphysis (contd. Ax’n)
•Maintaining bone mass:retard bone resorption,
expression of bone matrix proteins & promotes +
calcium balance by inducing renal hydroxylase enz
• Salt & water retention, edema & rise in B.P.
•Impaired glucose tolerance(high dose of E & P)
• Blood coagulability(dt ind of syn ofclottingfactors)
• HDL & Tg and LDL is decreased
• Cholesterol content of bile
• Thyroxine & cortisol binding glob. are elevated
Oestrogens: Actions

10. Adverse effects of Oestrogen
• Nausea, vomiting, anorexia, diarrohoea
• Libido, gyaecomastia & feminization (male)
• Stunted growth
• Adenocarcinoma of vagina & cervix ( offspring)
• Postmenopausal : endometrial cancer
• Premenopausal : Ca. breast preexisting
• Coronary & thrombo-embolic disorders
• Gall stone
• Benign hepatoma
• LDL and HDL & TG, hyperglycaemia

11. •Substitution therapy:
menopausal
syndrome
Senile vaginitis
delayed puberty
•as oral contraceptive
steroids
•dysmenorrhea
•dysfunctional uterine
bleeding
•acne
•hirsutism
•osteoporosis
•prevention of heart
attacks
•Ca. of breast
•Ca. of prostate
• postpartum lactation
Clinical uses of Oestrogens

12. Hormone Replacement Therapy
Benefits:
•Relief of hot flushes &vasomotor symptoms(in
peri menopause:cyclic HRT)
•Young women with premature menopause
•Osteoporosis (before bone loss.
Bisphosphonates)
•Does not protect against cognitive decline
•Combined HRT inc. risk of breast cancer,
gallstones & migraine
•Transdermal HRT may have advantage over
oral

13. Cardiovascular events
•Improves HDL:LDL
•Retardsatherogenesis
•Red. arterial
impedance
•Prevents
hyperinsulinemia
•Reduction in MI,
CAD, stroke(within 10
yrs)
•Triples risk of venous
thromboembolism
•Inc. risk of MI in 1
st
yr
& no prophylaxis for
CAD (PROGESTIN)

14. Tibolone
•19- norsteroidal drug
•Oestrogen + progesterone + weak androgen in sp ts
•Preparation: 2.5mg tab.
Use: HRT (menopausal symptoms, urogenital atrophy, psychological
symptoms, libido and osteoporosis improved)
ADR: weight gain, increased facial hair, occasional vaginal
spotting
C/I: hormone dependent malignancy of breast, uterus,
undiagnosed vaginal bleeding, thromboembolic disease,
severe liver disease, migraine, epilepsy

15. Transdermal estradiol
•Patch in 3 sizes: 5, 10, 20cm2
delivering .025, .05, .1 mg in 24 hr for 3-4
days
•Usual dose in menopause is .05 mg
/dcyclic therapy 3 wks on, 1 wk off is
advised with oral progestin for last 10 -12
days
•Systemic side effects are same but less
severe
•Risk nof thrombo embolism not inc.

16. Antioestrogens
Anti-Oestrogens
• Clomiphene citrate
• fluvestrant
SERM
• Tamoxifen citrate
• Raloxifene
• Ormeloxifene

17. Clomiphene Citrate PURE estrogen #
Binds to ER AL & B
•Acts as oestrogen
antagonist
Mechanism:
• GnRH & Gn release by#
inh. feedback
Uses:
•Sterility
•Ca. breast
•In vitro fertilization
•Male infertility
ADME:
•p.o. – good absorption
•t½: 5 – 7 days
•adipose tissue
Side effects:
Polycystic ovary, multiple
pregnancy, gastric upset,
vertigo, dermatitis ,hot
flushes,
Cyclofenil: similar to clomiphene but no peripheral
anti-oestrogenic effects

18. Fluvestrant SERDs
•Selective estrogen
receptor down-
regulator
•Pure estrogen
antagonist
•Inhibits ER
dimerization &
receptor degradation
enhanced,complete
supp. Of ER fn.
•USE
•Rx of metastatic ER
+breast ca in
postmenopausal who
aren’t responding to
tamoxifen
•250mg I/M monthly inj

19. SERMs selective estrogen
receptor modulator
•Tamoxifen citrate
•Raloxifene
•Toremifene

20. Tamoxifen citrate
•Potent estrogen ant. at brest
cancer cell,BVs but partial
agonist in uterus, bone, liver
• proliferation of breast cancer
cells andhot flushes
Stim. of endometrial proliferation
• Anti resorptive
•Dec total cholesterol and LDL
• No change in HDL and TGs
• risk of DVT & pulmonary
embolism
•Given orally
•Metabolised in liver to a more
potent 4 OH-tamoxifen
•Undergoes enterohepatic
circulation
Uses
•Palliative therapy for advanced
CA Breast
•Hormonal treatment for both
early and advanced CA Breast
in women of all ages
Adverse effects
•Hot flushes, vaginal discharge,
cataract, nausea

21. Response rate:
ER +ve: 50%
ER & PR +ve: 60-70%
ER –ve: 10%
For 5 years :
Recurrence by 47 – 50%
Death 26 -28
Contralateral Ca. breast 47%
Tamoxifen citrate

22. Raloxifene
•Bone & CVS: partial
agonist
•Endometrium & breast:
antagonist
•Postmenopausal women:
prevents bone loss
•Reduce LDL cholesterol
•65% reduction in risk of
breast cancer
•No increased risk of
endometrial cancer
•No relief of vasomotor
symptoms
•60 mg tab; Orally
absorbed
•high first pass
metabolism
Side effects: 3 fold increase
in deep vein thrombosis &
pulmonary embolism
(same as oestrogen HRT)
• Effective alternative to HRT
for prevention of and treatment
of osteoporosis

23. Ormeloxifene
•Endometrium & breast: antagonist
•Excessive bleeding with anovulatory cycle at
menopause is regularized.
But vaginal epithelium & cervical mucus is not
altered.
•Used for treatment of DUB
•60 mg tab;
•120 mg twice a week for 2-3 months
Side effects:
nausea, headache, fluid retention,
wt. gain, rise in BP, prolonged menstrual cycle

24. Aromatase inhibitors
•Letrozole
•Anastrozole
•Exemestane
•Effective in tamoxifen
failure cases of
advanced breast ca
•No deterioration of
lipid profile
•No inc risk of
thromboembolism,en
do. hyperplasia
•Inhibits prod. Of
estrogen in all ts.
•Not in pre menopause
•More effective in
delaying recurrence in
early stage ca
•Continues prophylaxis
beyond 5 yrs
•Greater delay in ds.
progression

25. letrozole
•Reversibly inhibits
aromatisation,within
brest ca cells,total
estrogen depletion
•1
st
line dg.for adjuvant
therapy for ER+
postmenopausal
•Extend beyond 5 yrs.
•Replace tamoxifen
after 2 yrs(sequential
•100% oral bioavail.
•Slow meta.
•1
st
line dg.advanced
breast cancer as
longer time to ds.
Progression & higher
response rate
•ADR: hot flushes,
thinning of hair,
jt.pain,acc bone loss
•Dose :2.5 mg oral

26. Anastrozole
•More potent than
letrozole
•Suitable for single
daily dose

27. Type Hormonal activitiesProgestOestrogenAndrogAnabolic
Progesterone derivatives
Progesterone
+ - - -
Hydroxyprogesterone Capr.
+ -
slight
-
Medroxyprogesterone acet
+ - + -
Megesterol acetate
+ - - -
Testosterone derivative
Dimethisterone slight
- - -
Nor-testosterone derivative
Norethynodrel slight
+ - -
Lynestrenol slight
+ + +
Norethindrone
+
slight
+ +
Ethynodiol diacetate
+
slight
+
Norgesterol
+ - + -

28. Progestrogen: Actions
Uterus:
 secretray changes (with oestrogen)
 If ovum is fertilized
 prepare endometrium
 oxytocin & ergonovine actions
 FSH, LH ovulation
 cervical secretion – thick and viscid
Vagina: WBC infiltration & cornified epithelium
Breast
Body temperature
Respiration
Pituitary

29. •as OCS
•DUB
•HRT
•dysmenorrhea
•premenstrual syndrome
•endometriosis
•threatened abortion
• post-partum
lactation
•endometrial cancer
•hypoventilation
Clinical uses of Progesterones

30. Adverse effects of Progesterone
• breast engorgement, headache, rise in body temp.,
oedema, acne & mood swings
• masculinization of external genitalia in the foetus
• Increased incidences of congenital abnormalities
• irregular bleeding or amenorrhea
• lower HDL (19-nortestosterone derivatives)
• hyperglycaemia

31. Pharmacokinetics
•Absorption:
•progesterone undergoes high first pass
metabolism. Therefore synthetic
preparations are more commonly used.
•Progesterone esters in oily soln. for i.m.
admn.
•Metabolism:
– by liver enzymes
–excretion by urine after conjugation

32. Antiprogestin
Mifepristone

33. Mifepristone
•19-nor-steroid derivative
Mechanism:
• Blocks progest. &
glucocorticoid receptors
•During luteal phase:
Pregest. PGs
Menstrual bleeding
•Sensitize myocardium to PGs.
•HCG production falls
ADME:
•F: 25 %, CYP3A4 metabolism’ t½: 20 h
Uses:
•Termination of early pregnancy –
along with prostaglandin
•As a cervical ripening agent
•Post-coital contraceptive
•Once a month contraceptive
•Progesterone sensitive tumors
•Cushing’s syndrome
Side effects:
Vomiting, diarrhoea, pelvic pain or
abdominal pain, about 5% have
severe vaginal bleeding

Precaution: Not to be given to a woman with suspected ectopic
pregnancy, hematological disorders, receiving oral anticoagulants,
Liver/renal diseases

34. Combined Oral Contraceptives

35. Introduction
World’s population expected to reach 9 billion by 2050.
India accounts for 18% of World’s population… !!!
Annually, 529,000 maternal deaths & 50 million
morbidity.
In India, contraceptive prevalence is 48.3% .
21% of all pregnancies resulting live births are
unplanned….!!!
If unmet need for contraception was met, we can avoid
52 million unwanted pregnancies
25-50% of maternal deaths
( Hindin MJ, Lancet.
2007;370:1297-8 )
Dr Shashwat Jani. 9909944160 36

36. Dr Shashwat Jani. 9909944160 37

37. 
1
st
Clinical trials of COC were
described by John Charles Rock &
Goodwin Pincus (progestins) with
approval of marketing in USA in
1960.
Addition of estrogen enhanced
efficacy
COC is used by over 100 million
women worldwide.
Dr Shashwat Jani. 9909944160 38

38. Combined Oral Contraceptives ( COC )
 Commonly known as the “ Pill “
Widely Accepted & Most Effective
Reversible method of Fertility
Control.
 In 1951, India was the 1
st
country in
world to introduce COC in National
programme of Family Planning.
39Dr Shashwat Jani. 9909944160

39. COC : Estrogen + Progestogen
 Estrogen :
2 types : - Ethinyl Estradiol
( EE )
- Mestranol ( Not
used )
Dr Shashwat Jani. 9909944160 40

40. Dr Shashwat Jani. 9909944160 41
•Estrogen content ranges from 20-
50 Ug
•Preparations containing <35 are
referred as LOW DOSE PILLS

41. PROGESTOGENS :
( 4 Groups )
1 ) Norethisterone Group : ( 1
st
generation Pills )
Moderate Androgenic property ….
Norethisterone,
Norethisterone Acetate ,
Ethiynoidal diacetate ,
Lynestrenol
2 ) Norgestrel : ( 2
nd
generation pills )
Strong Progestogenic & Androgenic property….

Dr Shashwat Jani. 9909944160 42

42. 3 ) 19 – nor testosterone derivatives :
( 3
rd
generation pills )
Anti ovulatory function by suppressing Gonadotropin…
Desogestrel,
Gestodene,
Norgestimate.
4 ) Spironolactone analogue :
Antiandrogenic & Anti mineralocorticoid …
Drosperinone ( DRSP )

Dr Shashwat Jani. 9909944160 43

43. Types of COC
45Dr Shashwat Jani. 9909944160

44. 1) Monophasic
 Contains Estrogen & Progesterone in same
amount in Each pill .
 Divided in 2 subgroups :
- Low dose pills : EE 30 – 35 microgm
- Very low dose pills : EE 15 – 25 microgm.
Mala - N
•dl – NGL 0.15 mg
•EE 0.03 mg
Mala - D
•l – NGL 0.15 mg
•EE 0.03 mg
46Dr Shashwat Jani. 9909944160

45. 2 ) Multiphasic
 Contains low or variable amounts of E and P in 2
( biphasic ) or 3 ( triphasic ) phases of cycles.
 Biphasic : constant EE – 35 microgm
progestogens : low in first 10 days
higher in next 11 days .
NOT POPULAR – MORE FAILURE RATE .
NOT AVAILABLE IN INDIA … 

47Dr Shashwat Jani. 9909944160

46.  Triphasic :
Triquilar –
- 0.03 EE +0.5mg l-norgestrel (1 - 6)
- 0.03 EE +0.75mg l-norgestrel (7-11)
- 0.03 EE +0.125mg l-norgestrel (12 - 21)
Total monthly intake – 0.68mg EE +1.92mg progesterone
•Adv. – high efficacy rates
- few side effects
- less break through bleeding
- does not affect s.cholesterol & LIPIDS
•Disadv. – high pregnancy rates if errors in pill intake .
48Dr Shashwat Jani. 9909944160

47. •TRANSDERMAL preparation of
norelgestromin and ethinyl estradiol
(ORTHO EVRA) is avail. For weekly
application to buttocks, abdomen,upper
arm or torso for first 3 consecutive weeks
followed by a patch free week
Dr Shashwat Jani. 9909944160 49

48. •Intravaginal ring containing ethinylestradiol
and estonogestrel is also available in 3
week on and 1 week off cycle.
Dr Shashwat Jani. 9909944160 50

49. •Progesterone only Pills
•Highly efficacious
•Block ovulation in 60- 80% of cycles
•Thicken cervical mucus
•Decrease sperm penetration
•Endometrial implantation
Dr Shashwat Jani. 9909944160 51

50. •Depot injections of MPA exert
similar effects
•Yield plasma levels of drugs high
•Prevents ovulation in almost all
pts.
•Decrease frequency of GnRH
pulses
Dr Shashwat Jani. 9909944160 52

51. PROGESTOGEN ONLY PILLS ( POPS)
•Types:
•Norethindrone 350Ug taken daily without
interruption
•Norgestrel subdermal implants (216mg)for
up to 5 yrs
•Etonogestrel 68mg (sub dermal) for 3 yrs
•Medroxy progesterone acetate crystalline
suspension for I/M inj for 3 months

52. •PROGESTASERT _an IUD which
releases low amounts of progesterne
locally
•Avail. For insertion on yearly basis
•Effective 97-98%
•MIRENA _ an IUD releases levonorgestrel
for upto 5 years
•All these act by producing local effects.
Dr Shashwat Jani. 9909944160 54

53. Emergency Contraception…
1) Yuzpe regimen –
0.1mg EE + 1 mg dl-Norgestrel
1
st
dose Within 72 Hrs of Contact
Repeated after 12 Hrs.
2) Ovral
1
st
dose 2 tablets within 72 hrs.
2
nd
dose 2 tablets after 12 hrs.
3) Overal – L
1
ST
dose 4 tablets within 72 hrs.
2
nd
dose 4 tablets after 12 hrs.
Dr Shashwat Jani. 9909944160 55

54. Emergency Hormonal Contraception
•Levonelle 1500 (one step)
•Contains high dose progesterone
(levonorgesterel)
•One 1500mcg tablet taken as soon as
possible after unprotected
intercourse (up to 72 hours after)
•Preferably within 12 hours, no later
than 72 hours

55. • Ulipristal SPRM SELECTIVE
PROGESTERONE RECEPTOR
MODULATOR 30 mg single dose as soon
as possible but within 120 hrs of contact.
•It is equally effective .well tolerated
•Extended window of protective action
•Mifepristone 600 mg single dose within 72
hrs is also used in Europe & China.
Dr Shashwat Jani. 9909944160 57

56. How does EHC work?
•Dependent on point in the menstrual
cycle
•Either prevents or delays ovulation,
prevents fertilisation or prevents
implantation of the fertilised egg into the
uterus.
•Clinical opinion is that EHC is not an
abortifacient

57. Mechanism of
action:
1 ) Inhibition of Ovulation :
 both hormones act on Hypothalamo
pituitary axis , suppress release of FSH &
LH from Ant. Pituitary.
E – inhibits FSH.
P – inhibits preovulatory LH Surge , less
effect on FSH.
59Dr Shashwat Jani. 9909944160

58. 2 ) Endometrial Hyperplasia :
 stromal oedema , decidual reaction &
regression of glands making endometrium
nonreceptive to embryo.
3 ) Cervical mucus :
thick , viscid , scanty .
impaired sperm transport & penetration.
4 ) May affect tubal motility & alter tubal
transport so that eggs cannot effectively
move towards uterus.
60Dr Shashwat Jani. 9909944160

59. How does it work?

60. Available Dosage forms
•Birth control (contraceptive) medications contain
hormones (estrogen and progesterone, or
progesterone alone).
• The medications are available in various forms,
such as pills, injections (into a muscle), topical
(skin) patches, and slow-release systems
(vaginal rings, skin implants, and contraceptive-
infused intrauterine devices

61. How to choose the drug?
•Choosing which estrogen and progesterone dose, type,
and administration method is
–Highly patient specific, meaning that the choice greatly
depends on factors unique to an individual.
•General goals are to choose a product that provides good
menstrual cycle control with the fewest adverse (side)
effects and to use the lowest hormone dose possible.
• After beginning birth control medications, it may be
necessary to adjust the dose or to choose a different
product.

62. Selection of the patient
 Detail history ( headache , migraine ,
etc…)
 Thorough general examination
( Breast , blood pressure… )
Pelvic examination to exclude cervical
pathology.
Cervical cytology
Rule out any other contraindications.
Dr Shashwat Jani. 9909944160 64

63. Checklist for Prescribing COC…
Last menstrual period, rule out pregnancy
Less than 6 months postpartum & lactating?
Age, Cigarette smoking, h/o migraine
Known case of diabetes or hypertension
History of stroke, MI or thrombosis
h/o jaundice/ liver disease
h/o breast/ genital tract malignancies
h/o drug intake: Antitubercular, antiepileptic
Dr Shashwat Jani. 9909944160 65

64. Administration
New User :
- 1
st
day of Cycle .
- Daily 1 tab. Preferably at night for consecutive 21
days.
- Continued for 21 days and then 7 days break ( with
iron tablets ) .
- Next pack of Pill should be started on 8
th
day ,
IRRESPECTIVE OF BLEEDING ( same day of the
week , pill finished ).
- Simple Regimen of “ 3 WEEKS ON & 1 WEEK OFF “
- No break between packs.

66Dr Shashwat Jani. 9909944160

65. Missed Tablets :
1 missed – Take 2 tablets next day .
2 or 3 missed – Take 2 tablets on two
consecutive days and continue the rest of
the pack.
+Another Contraceptive for 1
week.
Dr Shashwat Jani. 9909944160 67

66. •Lactating Women – Progestogen only pills
/
Combined pills after 6
months
•Non Lactating Women – Combined oral
pills after 3 to 6 weeks or after
menstruation
•1
st
/ 2
nd
Trimester abortion – during first 7
days.
•Amenorrhea : At any time after excluding
pregnancy + barrier method for 7 days.
68Dr Shashwat Jani. 9909944160

67. Follow up …
 Examined after 3 months , then after
6 months and then yearly .
 Ask for any symptoms…
 Examination for breast , pelvis, BP &
weight & cervical cytology.
Dr Shashwat Jani. 9909944160 71

68. Effectiveness…
Failure rate : 0.1%

Failure rate
are mainly due to
missed pills.
72Dr Shashwat Jani. 9909944160

69. How long can be continued
…???
In properly selected patient without
any risk factor , benefits are more ,
and so can be continued up to age
of 50 with careful monitoring.
Offers dual advantage of
Contraception and HRT.
For spacing of birth : 3 – 5 years.
73Dr Shashwat Jani. 9909944160

70. Advantages of COCs
1.Highly effective if used correctly.
2.Rapid return of fertility after stoppage.
3.Suitable for nulligravida and newly
married couples.
4.Completely controlled by the woman and
can be stopped at any time unlike other
methods (IUD & Implants).
5.No need to do any thing at the time of
intercourse.

71. Advantages…
•Prevention of pregnancy
India - MMR is high &
2/5
th
of these deaths can be prevented by
use of OCs
•Cyclical Stabilisation
Great social advantage.
Withdrawl bleeding is
predictable & postponed safely by taking
more low dose pills contineously .
75Dr Shashwat Jani. 9909944160

72. •Cure of Menstrual Disorders

Dysmenorrhoea & Ovulation pain – By inhibiting ovulation &
production of PG .

Menorrhagia & Metrorrhagia - Norgestrel High dose oral pills more
useful.
Lessens PMT.

•Protection against Cancer
a) Endometrial cancer- Reduction by 50 %
effect persists for 15 yrs.
b) Ovarian Cancer – Reduction by 40 %

effect persists for 10 yrs.
c) Choriocarcinoma – Indirectly prevention by preventing
pregnancy.
76Dr Shashwat Jani. 9909944160

73. •Protection against benign tumors
1) Fibrocystic and Fibroadenomatous
disease
2) Ovarion Functional Cysts
1) Follicular Cyst – 50 %
2) Corpus Luteum Cyst – 80 %
3) Fibroid Uterus - Reduction by 30%
Low Dose OC’s reduce fibroid ( WHO
1996)
77Dr Shashwat Jani. 9909944160

74. •Protection against diseases
1) Ectopic Pregnancy
2) PID
3) Anaemia and Malnutrition
4) Endometriosis
5) Acne and Hirsutism(anti androgenic
progestin Drosprirenone)
6) DUB
7) Osteoporosis
•Simplicity and Attractiveness
•No Affection on Future fertility ( 3 months )
78Dr Shashwat Jani. 9909944160

75. Minor Side Effects…
•Nausea, Vomiting and Lack of appetite
•Break through bleeding (progestins)
•Menorrhagia and irregular bleeding
•Oligomenorrhoea and Amenorrhoea(inj./ mini pill)
•Breast changes – Heaviness and Tenderness
•Headache and Migraine
•Chloasma(similar to as in pregnancy)
•Wt. Gain, acne & inc. body hair(androgenic axn of
older pills)
•Mood changes
79Dr Shashwat Jani. 9909944160

76. Major Side Effects…
•Cardiovascular Diseases
1) MI – Increased Risk in heavy
smokers
2) Haemorrhagic or Ischemic Stroke –
2-6 fold
3) Venous Thromboembolism – Risk
increases with age, diabetes,
hypertension & smoking.
80Dr Shashwat Jani. 9909944160

77. •Estrogen is responsible for venous
thromboembolism
•Estrogen & Progestins both for arterial
thrombosis
•Mechanism involved :
•Inc. in blood clotting factors
•Decrease antithrombin III
•Decrease plasminogen activator in endothelium
•Increased platelet aggregation
Dr Shashwat Jani. 9909944160 81

78. •Hypertension - in 5-10% women
•Lesser incidence with low dose pills
•Stop Ocs—BP normalises in 3-6 months
•Both hormones probably increase
plasma angiotensinogen level & renin
activity_ salt & water retention.
•Llipid Profile – Triglycerides may inc.
marginally.Estrogens inc.HDL/LDL
RATIO but progestins nullify it.
Dr Shashwat Jani. 9909944160 82

79. •GENITAL CARCINOMAS
INCREASED INCIDENCE of vaginal,
cervical & breast cancer in animal studies
but not seen in general population
RISK IS INCREASED IN PREDISPOSED
INDIVIDUALS
Minor increase in Breast cancer
Dr Shashwat Jani. 9909944160 83

80. •BENIGN HEPATOMAS
•Higher in OC users
•GALLSTONES
•ESTROGENS INCREASE BILIARY
CHOLESTEROL EXCRETION
Dr Shashwat Jani. 9909944160 84

81. Interaction With Drugs…
ENZYME INDUCERS
Phenytoin,phenobrbitone.carbemezepine &
rifampicin incm metabolism of hormones
and cause failure of contraception.
SUPPRESSION OF INTESTINAL
MICROFLORA
Ttc, Ampicillin_deconjugation of estrogen
excreted in bile fails to occur, enterohepatic
circulation is interrupted & blood levels fall.
85Dr Shashwat Jani. 9909944160

82. Absolute Contraindications
•Thromboembolic, coronary and
cerebrovascular ds or a history of it
•Suspected/ overt malignancy of genitals/
breast
•Porphyria
•Moderate to severe hypertension
•Congenital hyperlipidemia
•Abnormal undiagnosed vaginal bleeding
Dr Shashwat Jani. 9909944160 86

83. Absolute Contraindications…
•Complicated valvular heart diseas
•Active hepatitis, liver tumors or H/O
jaundice in past pregnancy
•Major Surgery---to avoid risk of
postoperative thromboembolism
•Prolonged Immobilization
•Porphyria
87Dr Shashwat Jani. 9909944160

84. Relative Contraindications
•Diabetes
•Obesity
•Smoking
•Age above 35 years
•Migraine
•Mild hypertension
•Uterine leiomyomas
Dr Shashwat Jani. 9909944160 88

85. Indications of Withdrawal :
 Severe migraine
Visual or speech disturbances
Sudden chest pain
Unexplained fainting attack or acute vertigo
Severe leg cramps
Excessive weight gain
Severe depression
Prior to surgery ( Atleast 6 weeks )

Patient wants pregnancy … 
89Dr Shashwat Jani. 9909944160

86. Non contraceptive uses …
•DUB
•Endometrial Hyperplasia
•Endometrios
•Reduce incidence of ovarian &
endometrial cancer
•Depot MPA reduce incidence of uterine ca.
90Dr Shashwat Jani. 9909944160

87. •Reduce incidence of ovarian cyst & benign
fibrocystic breast disease
•Regular menstrual cycle,reduced blood
loss and less iron deficiency anemia
•Less dysmenorrhoea
•Less PID & ectopic pregnancy
Dr Shashwat Jani. 9909944160 91

88. Long-Acting, Injectable, Progesterone-Only
Contraceptives
•Medroxyprogesterone acetate (Depo-Provera)
•Use:
–The first injection is given within 5 days following the onset of menstruation.
–After that, an injection is needed every 11-13 weeks.
 
•Side effects:
–Since progesterone is the only hormonal ingredient, estrogen-related side effects are
avoided.
– A side effect unique to this method of birth control is that most women eventually
stop having their periods.
–Depo-Provera may last in the body for several months in women who have used it on
a long-term basis and can actually delay the return to fertility after stopping the drug.
– Approximately 70% of former users desiring pregnancy conceive within 12 months,
and 90% of former users conceive within 24 months. Other side effects include
weight gain and depression.

89. Combined Injectable
Contraceptives
•CYCLOFEM :
- DMPA 25 mg + Ostradiol cypionate 5
mg.
• MESIGYNA :
- NET- EN 50 mg + Oestradiol valerate 5
mg.
•Given within first 5 days of menstruation
•Next dose on same date of each month.
93Dr Shashwat Jani. 9909944160

90. New formulation of Depo-Provera:
Depo-subQ Provera 104, for delivery with Uniject
Depo-subQ Provera 104:
tNew formulation for subQ injection
t30% lower dose (104 mg vs. 150 mg)
tRapid onset of action
tSame effectiveness, same length of protection (>3
months)
tApproved by USFDA (2005) and UK
tPotential for home- and self-injection
tAvailable for roll-out in 2011; Acceptability studies to
begin in mid-2010
Uniject:
t Single dose, single package
t Prefilled, sterile, non-reusable
t Short needles for subQ injection (easier use by non-
clinical personnel/CHWs)
t Compact; easy to use and store
Potential “home
run”

91. LNG ROD
•Implant with total 150 mg of LNG
( 75 mg / rod ) is found effective for 5 years.
UNIPLANT
•Single rod implant
•Nomegestrol 38 mg.
•Releases 100 microgm / day.
•For 1 year.
95Dr Shashwat Jani. 9909944160

92. Transdermal delivery system
•Nestorone ( newer progestin ) :
- Available as Cream & Patch.
- Patches used like pills : 3 weeks ON 1
week OFF.
96Dr Shashwat Jani. 9909944160

93. Topical Contraceptive Patch
•Norelgestromin/ethinyl estradiol (Ortho Evra)
–The topical patch may be applied to clean, dry skin on the shoulders,
upper arms, buttocks, or abdomen.
–It should not be applied to red or inflamed areas of the skin or in areas
where tight clothing may rub.
–The patch may be less effective in women weighing more than 198
pounds (90 kg).
•Use:
–A new patch is applied on the same day of the week, each week for 3
weeks in a row.
–The first patch is applied either on the first day of the menstrual period
or on the Sunday following menses.
– On the fourth week, no patch is applied.
–Menstruation should begin during this time.
–This 4-week period is considered 1 cycle.
–Another 4-week cycle is started by applying a new patch following the 7-
day patch-free period.

94. NEWER
CONTRACEPTIVES
Dr Shashwat Jani. 9909944160 98

95. Centchroman ( Saheli )
•Ormeloxifene .
• research product of CDRI , Lucknow
•Non steroidal , potent anti estrogenic ,
weak estrogenic.
•Prevent implantation of fertilized ovum .
•Orally 30 mg twice weekly for first 3
months then once a week.
•Avoided in PCOD, liver , kidney disease.
99Dr Shashwat Jani. 9909944160

96. MALE
 GOSSYPOL :
- A Chinese drug … !!! 
Nonsteroidal compound
- extract from Cotton seed.
- Oral 10 – 20 mg daily for 3 months then 20 mg
twice weekly.
Infertility develops after a couple of months
- Inhibit Spermatogenesis by toxicity on
seminiferous tubules & reduce sperm motility.

100Dr Shashwat Jani. 9909944160

97. •Fertility is restored several months after
discontinuation
•10% of men remain oligozoospermic
•During treatment serum LH &
Testosterone levels do not change
•Libido and potency not affected
•SIDE EFFECTS: Hypokalemia(dt renal
loss of K)
•Muscular weakness,edema,
diarrhoea,neuritis
Dr Shashwat Jani. 9909944160 101

99. Dr Shashwat Jani. 9909944160 103

100. RISUG :
- “Reversible Inhibition of Sperm Under
Guidence . “
- Developed by IIT & AIIMS.
- clear polymer gel made of Styrene maleic
anhydrate ( SMA ) mixed with Dimethyl
Sulphoxide ( DMSO ) injected in to Vas
deferens  partially blocks Vas , preventing
sperm from coming in to ejaculate.
- Phase I & Phase II trials cleared.
- VASALGEL is similar to it.
107Dr Shashwat Jani. 9909944160

101. Intra Vas Device ( IVD ) –
Shug :
- 2 devices inserted in to each Vas .
- Needs special surgical skill.
- wider trials needed.
108Dr Shashwat Jani. 9909944160

102. Voegeli’s Heat Method
• A small increase in the temperature of the testes has a
large negative impact on the production of sperm
(spermatogenesis).
•Voegeli’s program for temporary sterilization is as follows:
“A man sits in a [shallow or testes-only] bath of 116
degrees Fahrenheit for forty-five minutes daily for three
weeks.
Six months of sterility results, after which normal fertility
returns.
For longer sterility, the treatment is repeated. ”
•.
109Dr Shashwat Jani. 9909944160

103. Artificial Cryptorchidism/ Suspensories
(a) testes in normal position;
(b) testes raised to near inguinal canal; testes held in
place with
(c) briefs with ring of soft rubber or (d) ring alone.
110Dr Shashwat Jani. 9909944160

104. Gendarussa
•First nonhormonal male contraceptive pills.
•Developed by Indonesia.
•Active ingredient in Gendarussa disrupts
an enzyme in the sperm head, which
weakens the ability of the sperm to
penetrate the ovum.
•The effect is short term and reversible –
having no effect on male hormones.
•Still under clinical trials…
111Dr Shashwat Jani. 9909944160

105. Nifedipine – CCB
•CCBs also partially block the calcium
channels within the cell membranes of
sperm. This affects sperm function rather
than production.
•A man taking nifedipine produces a normal
amount of sperm, and the sperm appear
functional when viewed through a
microscope. But
 
in vitro 
tests show that
these sperm cannot fertilize an egg.
112Dr Shashwat Jani. 9909944160

106. Male Vaccines …
•Scientists are trying to isolate, identify,
and produce Anti sperm surface antigens
which will hinder sperm – egg without side
effects.
•Will take long time…
113Dr Shashwat Jani. 9909944160

107. Other Ongoing trials…
•Use of following as Male Contraceptives…
1 ) Neem extracts.
2 ) retinoic receptor antagonist
3 ) papaiya seed extracts
4 ) olealonic acid
114Dr Shashwat Jani. 9909944160

108. FEMALE
Many researches are
going on for development of
newer Contraceptives for females
which are either Non Hormonal
OR having low dose of Estrogen
and newer Progestogens.
115Dr Shashwat Jani. 9909944160

109. PATH Women’s Condom
•Polyurethane condom
pouch
• Foam dots improve
adherence to vaginal
walls
• Soft outer ring
• Dissolving capsule
116Dr Shashwat Jani. 9909944160

110. SILCS Diaphragm
• Cervical barrier device
• One-size-fits most
• Developed with input
from women and men
in multiple countries
• Regulatory application
in Europe & US.
117Dr Shashwat Jani. 9909944160

111. VAGINAL RINGS
•LNG ring covered by silastic
tube .
•Delivers 20 microgm / day
•Replaced every 3 months.
118Dr Shashwat Jani. 9909944160

112. Combined Ring – NUVA RING :
•Soft, transperent, ethinyl
vinyl ring
•Releases EE 15 microgm
+ Etonogestrel daily over
a period of 21 days.
•Then removed , after 1
week ( bleeding ) new
ring inserted.
•S/E : headache,
leucorrhea, vaginitis
Dr Shashwat Jani. 9909944160 119

113. Biodegradable
•Cipronor ( Single Capsule) – IMPLANTS :
- LNG 26 mg
- begins to disappear after 12 months.
•INJECTABLE :
-Microsphere of 0.06 – 0.1 mm diameter with
Norethindrone with or without EE.
-Given over Gluteal muscle.
-Once injected , can’t be removed.
120Dr Shashwat Jani. 9909944160

114. Quinacrine pellet
•It acts as Sclerosing agent
•Inserted transcervically through
hysteroscope in proliferative phase.
•Repeated in next cycle.
•Long term results are awaited.
121Dr Shashwat Jani. 9909944160

115. Frameless IUD - Gynefix
•Made of 6 copper beads ( 330 sqmm of
Cu ) on monofilament polypropylene
thread.
•Thread is knotted at one end , embeded in
to fundal myometrium up to 1 cm.
•Reduced risk of Expulsion,
Dysmenorrhoea, Bleeding , Infection.
•Can be used in Nulliparous.
•Removed with Hook.
122Dr Shashwat Jani. 9909944160

116. Gynefix
Dr Shashwat Jani. 9909944160 123

117. ESSURE
•Transcervical sterilisation
•4 cm long , 2 mm
diameter microcoil
•Spring like device
•Inserted in each fallopian
tube through
hysteroscope.
•Tube is blocked
permanently when scar
tissue grow inside.
124Dr Shashwat Jani. 9909944160

118. Dr Shashwat Jani. 9909944160 125

119. Drugs acting on uterus

120. UTERINE STIMULANTS
•Called as abortifacients/ oxytocics/ ecbolics
•Posterior pituitary hormone: Oxytocin,
Desamino oxytocin.
• Ergot alkaloids: Ergometrine (Ergonovine),
Methylergometrine.
•Prostaglandins: PGE2, PGF2α, 15-methyl PGF2α,
Misoprostol.
•
Miscellanous: Ethacridine, Quinine.

121. OXYTOCIN
•A posterior pituitary hormone
•An octapeptide
Synthesis
•Synthesized in supra optic and para ventricular nuclei of
hypothalamus and then secreted by post-pituitary
Stimuli for secretion (cuddling hormone)
•Coitus, parturition, suckling of an infant

122. OXYTOCIN
Pharmacokinetics
•Given intravenously/ intranasaly
•Nil plasma protein binding
•Catabolised via kidney and liver
•T1/2= 5 min
•Onset of action – 1min.
•Duration of action – 30min.
•Plasma half life – 12-17m

123. OXYTOCIN
Pharmacological Actions:
•Uterus: Oxytocin increases the force and frequency of uterine
contractions like a physiological labour i.e relaxation between
contractions. Estrogen sensitizes the uterus to oxytocin. Non-
pregnant uterus and uterus during early pregnancy is resistant.
•Breast: Milk ejection reflex. Contracts myoepithelial cells of
mammary alveoli
•CVS: Higher doses cause vasodilatation by direct action – brief
fall in BP, reflex tachycardia and flushing
•Kidney: Oxytocin exerts ADH like action – urine output is
decreased leading to pulmonary edema.

124. OXYTOCIN
Therapeutic uses
•Induction of labour in case of prematurity, in toxemia of
pregnancy, diabetic mother erythroblastosis, placental
insufficiency etc.
• Uterine inertia: It is preferred over ergometrine due to
–Because of short t1/2 and slow i.v infusion, intensity of
action can be controlled and action can be quickly
terminated.
–Low concentrations allow normal relaxation in between
contractions.
–Lower segment is not contracted: fetal descent is not
compromised.

125. OXYTOCIN
Physiological role
•Labour: obligatory for initiating parturition.... Labour
prolonged in its absence. PGs complement oxytocin
•Milk ejection reflex: suckling by infant– stimulate
mechanoreceptors in nipple--- signal hypothalmus
•Neurotransmission: regulate autonomic flow

126. OXYTOCIN
Therapeutic uses
•Post partum hemorrhage, Ceasarean section: Ergometrine
is generally preferred but oxytocin may be injected i.v for
immediate response.
• Midtrimester abortion but require oestrogen sensitized
uterus, thus prostaglandins prefered
•Breast engorgement (may occur due to inefficient milk
ejection reflex) – oxytocin is given as intra nasal spray few
minutes before sucklings
•Oxytocin challenge test to assess uteroplacental
insufficiency: oxytocin leads to marked increase in fetal
heart rate

127. OXYTOCIN
•Adverse drug reactions
•Injudicious use of oxytocin during labour can produce too
strong uterine contractions forcing the presenting part
through incompletely dilated birth canal (cause
premature birth & foetal death).
•Water intoxication: because of ADH like action of large
doses given along with i.v fluids specially in toxemia of
pregnancy and renal insufficiency.

128. OXYTOCIN
Side effects
•Hypotrension, Increased pulse rate.
•Nausea, vomitting, Anorexia, Constipation.
•Jaundice, Skin rash.
•Asphyxia, hypoxia.
Contraindications
•Hypersenstivity.
•Foetal distress.
•Severe toxemia.
•Patient with uterine surgery and uterine sepsis.

129. Available as:
•Inj Pitocin 10 IU/ml.
•Inj Syntocinon 5 IU/ml.

130. Desamino oxytocin
•Action is similar to Oxytocin.
•Available as Buctocin buccal tablet 50
IU.
•Uses
–Induction of labour. 50 IU buccal tab
repeated every 30min. Maximun
10tabs/day.
–For breast engorgement 25-50 IU just
before breast feeding.

131. ERGOMETRINE
•Ergot is a compact mycelium of a fungus Claviceps purpurea,
used by dais in rural India.
•Ergometrine is an amine alkaloid of ergot. It is also known as
ergonovine
Pharmacological actions
•Uterus: increase force, frequency and duration of uterine
contractions. Gravid uterus is more sensitive specially at
term and in early puerperium. It also involves the lower
segment.
•Low dose: contraction with relaxation
•High dose: contraction (no relaxation)

132. ERGOMETRINE
Pharmacological actions
•CVS : They are much weaker vasoconstrictors leading to
increase blood pressure
•CNS : Partial agonistic/ antagonistic interaction with adrenergic,
serotonergic and dopaminergic receptors in the brain.
•GIT : High doses can increase peristalsis leading to diarhea
Pharmacokinetics
•With IV onset of action immediate.
•IM: 2-5 min.
•Duration of action 45min.
•Metabolized in liver. Excreted in kidney

133. ERGOMETRINE
Caution in
•Patients with vascular disease, hypertension and
toxemia.
•Presence of sepsis – may cause gangrene.
•Liver and kidney disease, anaemia, asthma, convulsions
Uses
•To control and prevent post partum hemorrhage
•After c-section / instrumental delivery to prevent uterine
atony.
•To ensure normal involution.

134. ERGOMETRINE
•Available as
–Tablet methergin contains 0.125mg
methylergometrine.(Methylergometrine
is 1½ times more potent than
ergometrine on uterus).
–Inj methergin 0.2mg/ml (1ampoule

135. PROSTAGLANDINS
•PGE-2, PGF-2 α and 15-methyl PGF-2α
Actions:
•Uterus: PGE & PGF stimulate the tone and amplitude of
uterine contractions. Cause ripening of cervix.
•Reproductive System: produce luteolysis, decrease
progesterone secretions, prevent the implantation of fertilized
ovum.
•CVS: PGE-2 & PGA-2 produce vasodilatations & fall in BP.
PGF produces vasoconstrictions.
Uses
•Therapeutic Abortions.
•Induction of labour.

136. TOCOLYTICS
•Drugs which decrease uterine motility. They have been
used to delay / postpone labour, arrest threatened
abortion and in dysmenorrhea.
1.
 Adrenergic agonists :
•
2
selective agents – salbutamol, terbutaline and
ritodrine are preferred drugs to suppress premature
labour.
•Isoxsuprine oral / i.m. has been used to stop threatened
abortion but efficacy is uncertain.

137. TOCOLYTICS
2.
 Magnesium sulfate :
•Used to control convulsions and to reduce BP in toxemia
of pregnancy.
•It also suppresses uterine contraction effectively.
•It can cause cardiac arrhythmias, muscular paralysis,
CNS and respiratory depression in mother as well as in
neonate.
•It is generally used when β agonists are contraindicated

138. TOCOLYTICS
3.
 Calcium channel blockers:
•These can reduce the tone of myometrium and oppose
contractions (postpone labour if used early enough).
•Tachycardia and hypotension may be prominent and
reduced placental profusion causing fetal hypoxia is
apprehended.
Oxytocin Antagonist : ATOSIBAN # oxytocin receptors and
supress premature contractions and postpone preterm
delivery. s/e : N,V, rash .

139. TOCOLYTICS
4.
 Prostaglandin synthesis inhibitor:
•Aspirin, ibuprofen and indomethacin can delay labour
before it has started.
•But it carries risks to mother and fetus (specially
intrauterine closure of ductus arteriosus and
oligohydramnios).
5.
 Ethyl alcohol given by i.v infusion stops labour but
produces marked maternal CNS depression.

140. TOCOLYTICS
6.
 Progesterone decreases sensitivity of the uterus to
oxytocin.
•It is frequently used for threatened / habitual abortion.
7. Miscellaneous drugs:
•Nitrites, diazoxide, anticholinergics, phenothiazines and
general anaesthetics reduce uterine contractions.
•Halothone is an efficacious uterine relaxant and has
been used as the anaesthetic when external or internal
version is attempted.

141. THANK YOU