recent advances in contraception

1. DR. PRIYANKA KUMAWAT
Pharamcology deptt.
PGIMS, Rohtak

2. World’s population expected to reach 9
billion by 2050.
India accounts for 17% of world’s
population.

3. 21% of all pregnancies resulting live births
are unplanned.
Around 2/5
th
of all pregnancies are
unintended.
If unmet need for contraception
was met, we can avoid
◦55 million unwanted pregnancies(71%)
◦22 million fewer abortions
◦90,000 fewer maternal deaths
◦3,90,000 fewer children who would lose
their mothers.

4. Unawareness
Use of traditional methods
Side effects
High cost
Difficult mode of delivery
Fear of irreversibility of fertility
Length of effctiveness(inconvenience to take pills daily)
Fear of problems associated with amenorroea

5. Slow the pace of population growth
Slow the pace of population growth
Decrease abortion related complications and deaths
Cut down maternal care costs
Promote better maternal health
Improve the health of children through provision of
better nutrition and other care
……..beneficial to the society at large!!!
Po

7. TEMPORARY
METHODS

8. All hormonal birth contol measures act via same
mechanism
Stops ovulation
Prevents uterus lining from build up
Making the cervical mucous thick to prevent
penetration of sperm

9. Monophasic pills
Biphasic pills
Triphasic pills
Progesterone only pills

10. Type Estrogen Progestin
Mala N EE 30 ugNorgestrel 300 ug
Mala D EE 30 ugLevonorgestrel 150 ug
Ovral L EE 30 ugLevonorgestrel 150 ug
Ovral G EE 50 ugLevonorgestrel 250 ug
Novelon EE 30 ugDesogestrel 150 ug
Femilon EE 20 ugDesogestrel 150 ug
Loette EE 20 ugLevonorgestrel 100 ug
Yasmin EE 30 ugDrospirenone 3 mg
Yaz EE 20 ugDrospirenone 3 mg

11. 
Comparable in efficacy to monophasic pillsComparable in efficacy to monophasic pills

It was introduced with an aim of reducing the total dose of It was introduced with an aim of reducing the total dose of
hormones per cycle and to ↓ BTB.hormones per cycle and to ↓ BTB.
Better carbohydrate and lipid profile.Better carbohydrate and lipid profile.
Type Estrogen Progesterone

Triphasic-
Triquilar
EE – 30 ug (D1-6)
EE – 40 ug (D7-11)
EE – 30 ug (D12-21)
Levonorgestrel 50 ug
Levonorgestrel 75 ug
Levonorgestrel 125 ug

12. Reducing the dose to the lowest possible without
reducing efficacy (10 fold reduction)
Norethisterone 350μg
Norgestrel 75μg
Levonorgestrel(LNG) 30μg
Dosing shedule-
Started on 5
th
day of menstruation normally
21 day of post partum period
Soon after abortion
Extra precaution for 2 days to be taken

13. POPs have no estrogen side effects.
POPs do not decrease breast milk production.
A woman’s periods may be lighter, shorter and
have less cramping.
POPs may be used by women:
Who are breastfeeding
Over 35 years who smoke
Have a history of blood clots in the veins
Have migraine headaches
Have a higher risk of heart attack or stroke
S/E- depression,irregular
bleeding,headache,migraine,weight gain,ectopic
pregnancy.

14. 1.Intermenstrual spotting
2.Amenorrhoea
3.Lactation suppression
4.Decreased libido
5.Nausea,vomiting
6.Liver adenomas
7.Gall stones
8.Carbohydrate intolerance
9.Abnormal lipid profile
10.Headache,depression,irritability,lethargy
11.Weight gain
12.Vascular thromboembolism

15. Estrogen-estradiol valarate along with newer progestin
(dienogest-DNG) is used.
Step down doses of estrogen and step up doses of progestin
preperation is used.
ADV-
-fewer spotting days,reduction in mean blood loss
-reduced breakthrough bleeding
-more increase in HDL(8%)
-stability in carbohydrate metabolism
-effective in treatment of heavy mensrrual bleeding
-significant improvement in Hb,hematocrit,ferritin levels

16. COMPOUN
D
DAYS ESTROGEN PRODESTE
RONE
E
2
V-DNG 1-2 3mg 2mg
3-7 2mg 2mg
8-24 2mg 3mg
25-26 1mg 3mg

17. SEASONALE-
150µg of LNG + 30µg of
EE
Taken continuously for 84
days, break for 7 days
Fewer periods (4 in a year)
Pearl index- 0.78
Breakthrough bleeding/
spotting – First few cycles
CONTINUOUS-
For 365 days
No break
0.09mg LNG+20μg EE
Less side effects
associated with hormone
withdrawl
Diminished breakthrough
bleeding after 8-9 months

18. Decreased incidence of:
1.Pelvic pain,
2.Headaches,
3.Bloating/swelling, and
4.Breast tenderness for women who experience these
symptoms during the pill-free interval;
Improved control over symptoms of endometriosis and
polycystic ovary syndrome; and
Greater convenience due to fewer withdrawal bleeds
per year.

19. Include little information on :
1.Long-term safety (although there are long-term
data for comparable total estrogen- progestin doses
per month)
1.Slightly higher cost for medications (an extra 3 pill
packages per year for a 91-day cycle).

20. These potential disadvantages must be weighed against
the likely reduction in the:

1.Cost of sanitary supplies
2.Pain medication
3.Time off work or school
4.More breakthrough bleeding initially
5.Possible delay in the recognition of pregnancy

22. a
a

24. Carcinoma endometrium – protective !!!
◦Use of COC for 12 months: 50% risk reduction
◦Protection persists 20 yrs after discontinuation

Epithelial ovarian cancers – protective !!!
◦Even 3-6 months use: 40% risk reduction (3 yr use- notable
impact, 10 yr use- 80% risk reduction)
◦protection continues 20 yrs after stopping.
 Colon & rectal carcinoma-protective!!!
- risk reduction by 37%!!!
 Indirectly prevents choriocarcinoma by preventing
pregnancy
Carcinoma liver-no association!!!

25. Carcinoma cervix – no definite association !!!
◦Detection bias due to increased screening with pap smear
◦No significant increased risk of invasive carcinoma cervix

Carcinoma breast – controversial, caution !!!
◦Current use: ↑early premenopausal ca breast, detection bias.
◦Past use: ↓ incidence metastatic postmenopausal ca breast
◦Known case of ca breast: COCs are C/I
◦BRCA1BRCA1 & & BRCA2BRCA2 carrierscarriers –50% 50% risk reduction for ca ovary vary
(baseline risk (baseline risk 45% & 25% in BRCA1BRCA1 & & BRCA2BRCA2 respectively)

Clear the confusion !!!
Cancers and COCs

26. Cycle-related:
◦Irregular cycles, dysmenorrhea, menorrhagia &anemia
◦Functional ovarian cysts
Prevention of:
◦Bone loss
◦Fibrocystic/benign breast disease
◦Pelvic inflammatory disease (PID), Ectopic pregnancy
Treatment of:
◦Acne, Hirsuitism
◦Perimenopausal symptoms

27. Should include the following:
1.Instructions on how to take the combined OC
2.Information on potential side-effects
3.Non-contraceptive benefits of the combined OC
4.Addressing common myths and misconceptions
5.Discussing risks and warning signs, including when to
seek medical care
6.Discussing what to do if pills are missed
7.Emphasizing dual protection (the combined OC with
condom use to prevent STIs and HIV infection)
8.Information about emergency contraception in the event
of missed pills

28. Progestin-only injectables:
◦Depot-medroxyprogesterone acetate (DMPA; “Depo-
provera”; Megestron®
150 mg given IM every three months
also SQ formulation, lower dose (104 mg); CBD …
◦NET-EN: norethindrone (or norethisterone) enanthate, Noristerat®)
given every two months
Combined injectable contraceptives (CICs, progestin plus
estrogen) — given monthly:
◦Cyclofem® (MPA, 25mg plus estradiol, 5 mg)
◦Mesigyna® (50 mg Norethindrone enanthate, plus 5 m.g.
estradiol)

29. Depo in Uniject

30. effectiveness-0.1-0.4 preg/HWY
reversibility- 6 WKS
Injectable sustained released preperation of DMPA
available as uniject
Inhibits Ovulation,follicular formation,thicken cervical
mucous
150 mg ,in 3months (14 day grace period)
Delayed Ovulation After Discontinuation
Main Side-Effects:
◦Amenorrhea
◦AUB
◦Weight Gain
◦Hair Loss

31. most suitable for women that require an
estrogen free birth control method:
◦women with a known sensitivity (allergic) to estrogen
◦women over the age of 35 years who smoke
◦women with migraine headaches
◦women who are breastfeeding
◦women who have endometriosis
◦women who have sickle cell disease
◦women taking anti-convulsant (for seizures)
medication

32. Reliable method of birth control.
Reduced risk of endometrial cancer and Pelvic
Inflammatory Disease (PID).
Reduced symptoms of endometriosis, PMS
and chronic pelvic pain,
Decreased incidence of seizures.
Possible decreased number of sickle cell crisis.
Periods may disappear after 9 to 12 months on
Depo-Provera.
Only need to get injection every 12 weeks.

33. Contraceptive patch(orth evra)
Transdermal gel
Transdermal spray

35. Effectiveness-0.8-1.3 preg/HWY
28 day regimen
Replaced every week
No patch free interval if only LNG 40μg is in it
21 day regime
Replaced every week
7 day patch free interval if EE 30μg+LNG 100 μg


ADV
Once a week dosing
,good compliance
Avoid first pass
metabolism
Progestin with minimal
androgenicity
DISADV
Patch is noticeble
High cost
Minor skin reaction
Room temperature storage is
necessory

37. Nestorone(NES) a progestin is used
Applied in dose 2.3 mg/day once for 21 days with
7 free days
Antiovulatory mechanism
Adv-
-no skin irritation
-regular bleeding pattern maintained
-No serious adverse events

39. MDTS-metered dose transdermal system
Spray delivers drug in skin with the aid of safe
enhancers forms reservoir in skin
drug slowly absorbed in the circulation over a period of
hours
Antiovulatory mechanism
3×90μl of NES(norethisterone) daily once application
S/E- bruising at the site,breast
tenderness,tearfullness,tiredness,headaches,dizziness
,vagueness.

41. Norplant
®
6 capsules
Effective 7 yrs
1-yr failure: 0.05%
(1 in 20,000); 5-yr.
failure 1.6%
Reg. approval in
62 countries
Insertion time: 4.3
min (0.8-18.0)
Removal time: 10.2
min (1.3-50m)
Cost: $27
Jadelle
®

2 rods
Effective 5 years
1-yr failure: 0.05%
(1 in 20,000); 5-yr
failure 1.1%
Regulatory approval
in 11 countries
Insertion time: 2 min
Removal time:4.9
min ± 3.5 minutes
Cost: $29
[Sinoplan: $5]
Implanon
®
 1 rod
 Effective 3 years
 Regulatory approval
in in 25 countries
 Insertion time: 1.1
min (0.03-5.0)
 Removal time:2.6
min (0.2 – 20.0)
 Cost: comparable;
AID RFA out now

43. Effectiveness- 92-97%
Failure rate- 1.2-1.5 preg/HWY
NES 150μg+15μg EE/day
21day/7 day
ADV-
-reused for a year
-reduced cost
-excellent bleeding
control
-rapid return of fertility
-no changes in weight
DISADV-
-feeling of ring on place
-difficulty in remembering to
reinsert

45. C31G Glyminox 1% Gel(savvy)
50-60% effective
1.2-1.5 preg/HWY
Vaginal microbicide(carrageenan,betacyclodextrin)
contraceptive along with spermicidal agent(nonoxynol-
9)
Applied 15 minutes prior to intercourse
Prevent from sexually transmitted diseases
MOA-
-boost bodies natural defense against infection
-damage and disable disease pathogen
-entry and fusion inhibitors
-replication inhibitors
ADV-
-women can control theselves its use
-No serious side effects

46. Failure rate-0.1-2.5
IUD impregnated with SPRM(selective
progesterone receptor modulator)-ulipristil
Act by suppression of ovulation,endometrial
atrophy

47. ESSURE- a spring like device plugged into
fallopian tube
QUINARINE- a chemical compound gel like
introduced
The ADINA procedure- a plastic implant is
inserted into a lesion in fallopion tube and tissue
grows into it and plug the tube

48. Currently available methods
-Condoms
-Gossypol
-vasectomy

49. Suppression of gonadotropin releasing hormone from
the hypothalamus and the gonadotropins, LH and FSH,
from the pituitary gland.
-Decreased LH-decreased testosterone production from
Leydig cells, low intratesticular testosterone level,
decreased Sertoli cell function and suppression of
spermatogenesis
-Decreased FSH results in Sertoli cell dysfunction and
impaired spermatogenesis ,
Decreased in spermatozoa production occurs via:
-Decreased proliferation of spermatogonia
-accelerated germ cell apoptosis
-defective spermiation

50. HORMONAL APPROACHES-
Testosterone enanthate,testosterone undecanoate wkly
injections
testosterone + progestin
-TE gel + inj DMPA
-TE inj/wk + LNG oral daily
-TU inj/8wk + LNG implant
-TE pellet(implant) +DMPA
GNRH antagonist s.c/day + TE inj/wk
S/E- weight gain,HDL suppression,prostatic hypertrophy
SARM-MENT(7α methyl-19-norgesterone) implants
-10 fold greater potency than testosterone
- additional 5α reductase inhibition property(minimize
prostatic problems)

51. NON HORMONAL

o Target sertoli cell-Indenopyridines(CDB4022) with
GNRH antagonist
oSpermatid sertoli cell interaction-Adjudin
oHE6 epididymal duct specific protein receptor
oCRISP-1 preventing initiation of capacitation during
sperm transit and maturation
oCatspers –allow Ca
++
entry in sperm tail
oCAMP-necessory for capacitation
oIZUMO-sperm specific membrane protein responsible
for sperm egg fusion
RISUG- a clear gel injected in vas blocks it
IVD-intra vas devices

52. Safe, effective and acceptable contraceptive vaccines
may be an attractive addition to the currently available
range of family planning methods in that they would:
Confer long-term (but not permanent) protection
following a single course of immunization.
Be free of overt pharmacological activity and the
metabolic and endocrine disturbances that often
accompany other methods of birth control.
Not require insertion of a device or implant.
Remain effective without continuous conscious action
by the user.
Be inexpensive to manufacture.

53. ANTI-SPERM VACCINES
-Research has focused on two types of sperm
antigens:
Functional antigens as the enzymes known to be
required for sperm metabolism (lactic
dehydrogenase-X) , involved in sperm-egg
interactions and the processes leading to
fertilization (acrosin and hyaluronidase).
Structural antigens such as the molecules
expressed on the sperm cell membrane and which
may be involved in gamete interaction and fusion.

54. ANTI-OVUM VACCINES
 antigen-focused on the surface antigen zona
pellucida (ZP), the jelly-like glycoprotein coat
surrounding the egg.
 To date, however, no convincing data have been
presented to indicate that it can inhibit fertility
without causing an inflammatory reaction in the
ovary which might be indicative of a risk of acute
ovarian disturbances or long-term
immunopathology.

55. ANTI-CONCEPTUS VACCINES
placenta-specific antigens
 structural antigens, forming part of the trophoblast cell
membrane
-Pregnancy-specific ß1 glycoprotein (SP-1) an
antifertility effect was observed when female baboons
and cynomolgus monkeys were actively immunized
with human SP-1, in the majority of cases (50-80%),
this effect was manifested as a late abortion.
Another placental antigen PP-5,when animal is
actively immunized with human PP-5 and a substantial
reduction in fertility was shown.
functional antigens, such as placental hormones, have
been evaluated.

56. HORMONAL PLACENTAL ANTIGENS
human chorionic gonadotrophin (hCG)-production or function
of hCG can be inhibited immunologically, the corpus luteum
would regress
One type of anti-hCG vaccine, developed by the Population
Council in New York and by the National Institute of
Immunology (NII) in New Delhi, is based on the whole beta
subunit of the hormone (ß-hCG) (21,22). The other type of
anti-hCG vaccine, developed with support from the WHO Task
Force on Vaccines for Fertility Regulation, is based on a
portion (the carboxyterminal peptide or CTP) of the beta
subunit of the hormone (ß-hCG-CTP)
All of these anti-hCG vaccines require multiple injections to
achieve and maintain levels of immunity that are considered
effective.

57. Endocr Rev. 2008 June; 29(4): 465–493.doi: 
10.1210/er.2007-0041
Contraception. 2010 November ; 82(5): 471–475.
doi:10.1016/j.contraception.2010.03.010
Home |2008 Archive |July 2008 |Barbieri 93 (7): 2439
Special Programme of Research, Development and
Research Training in Human Reproduction,World
Health Organization, 1211 Geneva 27, Switzerland
Expert opinion,Emerging Drugs(2011)16(2):373-387
Shaw’s textbook of Gynaecology