This document discusses recent advances in contraception methods. It begins by outlining the need for contraception given projections of global population growth. It then categorizes contraception methods as temporary or permanent, and as female-oriented or male-oriented. The majority of the document provides details on various hormonal and non-hormonal contraception methods for both females and males, including mechanisms of action, dosages, effectiveness, advantages, and disadvantages. It covers oral contraceptives, implants, IUDs, patches, vaginal rings, injections, and emerging methods like transdermal gels and sprays. The document concludes by emphasizing the importance of contraception in managing global population.

1. Recent advances in
contraception Dr. Siddhartha Dutta
MAMC,
New Delhi

2. Outline
Introduction
Contraception types
Mechanism
Female contraception
Male contraception
Immuno- contraception
Conclusion

3. Contraception : need of the hour
• World’s population expected to reach 9 billion
by 2050
• India accounts for 17% of world’s population
• 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

4. IDEAL CONTRACEPTIVE
Safe Effective Acceptable
Inexpensive Reversible
Simple to
administer
Independent
of coitus
Long lasting to
avoid frequent
administration
Requiring little
or no medical
supervision

5. Contraception
Female/ Male
Temporary
Barrier Hormonal IUD
Permanent
Vasectomy
Tubectomy

6. Temporary
methods
• Condoms
• Diaphragms
• Cervical cap
Barrier
• OCP
• Implants
• Injectables
• Orthoevra patch
• Nuvaring
Hormonal
• Copper T
• Progestrasert
• Lipple’s loop
IUD

7. Hormonal
contraception
•All hormonal birth control
measures act via same
mechanism
•Stops ovulation
•Prevents uterus lining from
build up
•Making the cervical mucous
thick to prevent penetration of
sperm

9. Oral
Contraceptives
Monophasic
pills
Biphasic pills
Triphasic pills
Progesterone
only pills

10. Monophasic pills
Low dose pills
EE= 30-35μg
Very low dose pills
EE= 15-25 μg

11. Yaz
• 20 μg EE and 3 mg Drosperinone
regimen
• 24 pills with active medication
• Once daily for 24 days in a row
• Only COC with reported evidence
for and approved indication in the
treatment of emotional and
physical symptoms of
premenstrual dysphoric disorder

12. Multiphasic pills
• Comparable in efficacy to monophasic pills
• Introduced with an aim of reducing the total dose of hormones per
cycle and to ↓ BTB
• Better carbohydrate and lipid profile
Type Estrogen Progesterone
Triphasic EE – 30 ug (D1-6) Levonorgestrel 50 ug
EE – 40 ug (D7-11) Levonorgestrel 75 ug
EE – 30 ug (D12-21) Levonorgestrel 125 ug

13. 4 phase pills
• Estrogen-estradiol valarate along with newer progestin (dienogest-
DNG) is used
• Step down doses of estrogen and step up doses of progestin
preparation is used
• Qlaira
• Dosing schedule
Days E₂ V DNG
E₂ V-DNG 1-2 3mg
3-7 2mg 2mg
8-24 2mg 3mg
25-26 1 mg
27-28 placebo

14. • DNG- least CVS & metabolic effects
• More increase in HDL(8%), LDL ↓(6.5%)
• Stability in carbohydrate metabolism
• No glucocorticoid, anti-mineralocorticoid or anti
estrogenic effects
• Reduced breakthrough bleeding
• Effective in treatment of heavy menstrual bleeding
• Significant improvement in Hb, hematocrit, ferritin
levels
ADVANTAGES-
• VTE ??
• Amenorrhea more common
DISADVANTAGES

15. Extended cycle regimen
SEASONALE
• 150µg of LNG + 30µg of EE
• Taken continuously for 84 days,
break for 7 days
• Fewer periods (4 in a year)
• Breakthrough bleeding/ spotting
– First few cycles
CONTINUOUS
• For 365 days
• No break
• 0.09mg LNG+20μg EE
• Diminished breakthrough
bleeding after 8-9 months

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

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

18. Adverse effects of OCP
Mild
• E-Nausea,
vomiting, breast
tenderness, mild
edema, migraine
• P- increased
appetite, wt.
gain, acne,
hirsutism,
decrease in
libido, increased
body temp.
Moderate
• E- vertigo, leg &
uterine cramps,
ppt of DM
• P- BTB, monilial
vaginitis,
amenorrhea
Severe
• E- TE, cholestatic
jaundice,
cholelithiasis,
hepatic
adenoma
• P- MI,
cerebrovascular
thrombosis

19. Progestin only pills
• Reducing the dose to the lowest possible without reducing efficacy (10
fold reduction)
•Dosing schedule-
• Started on 5 th day of menstruation
normally
• Strict compliance(< 3 hrs window)
• 21 day of post partum period
• Soon after abortion
• lactation
• Extra precaution for
2 days to be taken
Norethisterone
350μg
Norgestrel
75μg
PoP
LNG
30μg

20. Desogestrel
• Suppress ovulation(97-100%) vs 40% with other pop
• 0.75 mg
• Thick mucus plug in the cervix
• ↑ tubal peristalsis
• Can be taken within 12 hrs window
Stringent time
not necessary
No androgenic
S/E-Acne
No ectopic
pregnancy
No altered
carb/lipid met
Failure rate is
low

21. Transdermal delivery
Contraceptive
patch(orthoevra)
Transdermal gel
Transdermal spray

22. Ortho evra patch
• Effectiveness-98-99%
• 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 DISADV
Once a week dosing- good compliance High cost
Avoid first pass metabolism Minor skin reaction
Progestin with minimal androgenicity Breakthrough bleeding and mastalgia

23. Gel
• Nestorone(NES) a progestin is used
• Applied in dose 2.3 mg/day once for
21 days with 7 free days
• Nestorone®/Estradiol Transdermal
Gel(Phase 3)
• Adv-
-No skin irritation
- Regular bleeding pattern
maintained
-No serious adverse event

24. Spray
• Metered Dose Transdermal System (MDTS) to administer a
pre-set dose of the Nestorone once daily to the skin (forearm)
• Phase 1
• Fast-drying spray & drug is slowly absorbed in the blood
over a period of hours
• Suitable for
• Breastfeeding mothers
• Who cannot tolerate contraceptive pills with estrogens
• Leaves no visible residue & less irritation than patches
• S/E- bruising at the site, breast tenderness, tiredness,
headaches, dizziness

25. Vaginal contraception- Nuva ring
• Effectiveness- 92-97%
• 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

26. Vaginal gel
C31G Glyminox 1% Gel(savvy)
50-60% effective
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
ADV-
• -Easy to use
• -No serious side effects

27. AG200-15 (Twirla™)
• Transdermal Contraceptive Delivery System
(TCDS)
• Low-dose, once-weekly patch
• EE + LNG
• Once weekly for 3 weeks, followed by a
week without a patch
• Minimizes seepage of adhesive around edge
of patch & ↓ chance of residue on skin
• Promote enhanced patient compliance
• Completed phase 3(FDA approval awaited)

28. IUD: LNG20
•Levonova
• 20mcg/day LNG -- Mirena
(52mg) over 5 years
• It releases 15µg of LNG per day
in vivo and is effective for 7-10
years
• Purpose:
• ↑ use from 5 to 7 years
• ↓ cost
• Study completion ~Dec. ‘18

29. Cyclofem
• Monthly injectable
• Pre-filled estradiol cypionate and
medroxyprogesterone syringes
• 25 mg MPA, 5 mg estradiol cypionate
• 94% to 99% effective at preventing
pregnancy
• Still to be introduced in US
• India- completed phase 3

30. Nestorone/EE 1 Year Ring (CVR)
• Nestorone/Ethinyl Estradiol
• 1-Year Ring (CVR)
• Releases 150 mcg Nestorone & 15 mcg ethinyl estradiol/day over 3-
week period
• 3 weeks in and 1 week out for 13 cycles
• Used like NuvaRing
• Lasts 13 cycles
• Awaiting FDA approval

31. Male
Hormonal
Contraception

32. Androgen formulations
• Dose interval- Oral, twice daily
• Potential concern- Twice daily dosing, short and
variable duration
Testosterone undecanoate
• Dose interval- Oral, daily
• Potential concern- Liver toxicity
17α-Methyltestosterone

33. Intramuscular
• Testosterone enanthate
• Dose interval-1–2 wk
• Overall contraceptive efficacy of
94.7%
• Potential concern-
• Delay in onset of full
contraceptive action for almost
3-4 months.
• Injections can be painful, high
peak levels
• Side effects from weekly injections
of 200 mg of TE in healthy men
include weight gain, a reversible
25% reduction in testicular
volume, a 6% increase in
hemoglobin, and a 10–15%
decrease in serum HDL cholesterol

34. Testosterone
decanoate
• Dose interval- 4–6 wk
• Potential concern-
Injections can be
painful, high peak
levels
01
Testosterone undecanoate
• Dose interval- 8–12 wk
• Potential concern- Injections
can be painful
• Weight gain, a 9% increase in
hemoglobin, and a 14%
decrease in HDL
02

35. Subcutaneous
• Dose interval- 4 months
• Dose of 600 mg is usually able to maintain plasma
testosterone level within physiological range for 4-5 month
• Potential concern- Surgical placement, occasional painful
expulsions
Testosterone implants
• Phase 2
• Dose interval- 6 months
• Surgical placement, poor sperm suppression, concern
regarding bone effects
MENT(7α-methyl-19-nortestosterone) implant

36. Transdermal
Testosterone
patch(non scrotal)
• Dose interval- daily
• Potential concern-
Poor efficacy, high
frequency of skin
irritation
Testosterone gel
• Dose interval- daily
• Potential concern-
Possibility of
partner transfer,
daily application
needed
Dihydrotestosterone
gel
• Dose interval- daily
• Potential concern-
Poor efficacy

37. Testosterone buccal
system
• Buccal
• Manufactured under trade
name Straint
• Applied twice a day
• Dose interval- Daily
• S/E-allergic reaction , Liver
toxicity

38. Nonhormonal Methods

39. Adjudin
Non hormonal
Analogue of lonidamine
Phase 2
Disrupt the interaction of spermatid-Sertoli cells
Binds to FSH receptor on Sertoli cell
As it does not affect spermatogonia themselves
the loss of fertility is reversible
Inj/ implant/ gel
Low oral bioavailability
Also know to be a potential anticancer drug

40. RAR
Antagonist
Sperm production
needs retinoic acid
Failure of
spermatids to align
and be released
into the lumen,
and aberrant
orientation to the
sertoli cells
1 week RAR
antagonist t/t– 3
month block
100% effective &
reversible in
animal models

41. Indenopyridine
Targets both sertoli cells and germ cell
Promising preclinical data for a potential
oral, non hormonal male contraceptive
MOA
• It activates the ERK/MAPK pathway, reduces
expression of prosurvival factors
• Alters expression of sertoli-germ cell adherens
junction proteins disrupts sertoli cell
microtubule structure
• Induces the proapoptotic factor, fas-result in
germ cell loss

42. Intra VAS device
• Non hormonal
• Injectable silicone plugs(Shug)
• 2 plugs blocks the sperm flow in vas deferens
• Reversibility not known
• There are two tested types of injected plugs
• Medical-grade polyurethane (MPU)
• Medical-grade silicone rubber (MSR)
• USA- silicon(phase 1)
• China- Polyurethane stent+ nylon mesh(phase 2)
• lower efficacy rate when compared to traditional
vasectomy

43. RISUG
Reversible inhibition of sperm under guidance
Polymer gel of styrene maleic anhydride+ DMSO
Injected into the lumen of the vas deferens using
a no-scalpel technique
Both partially occlude the vas deferens, while also
deactivating the sperm that are able to pass through
the partially occluded vas deferens, thereby preventing
successful fertilization
India- phase 3
Reversible by flushing with NaHCO3
S/E- transient painless scrotal swelling

44. Targeting sperm
motility
• Catsper blocker
• Sperm-specific transmembrane
proteins-allow Ca++ entry in sperm
tail
• The rise in intracellular calcium
mediated by the catspers is directly
responsible for the increase in
flagellar beat frequency that
characterizes sperm hyperactivation

45. IMMUNO-CONTRACEPTION
IMMUNO CONTRACEPTION

46. ANTI-SPERM VACCINES
2 types of sperm antigens
Functional antigens as the enzymes known to be required for sperm
metabolism (lactic dehydrogenase-XLDH-C4)
Involved in sperm-egg interactions and the processes leading to fertilization
(acrosin and hyaluronidase)
Structural antigens- expressed on the sperm cell membrane and which
may be involved in gamete interaction and fusion
Two sperm antigens identified- SP-10 and PH-20, have been shown to have
promising antifertility effects when injected into laboratory animals

47. ANTI-OVUM
VACCINES
Antigen-focused on the
surface antigen zona
pellucida
Causes an inflammatory
reaction in the ovary which
might be indicative of a risk
of acute ovarian
disturbances or long-term
immunopathology

48. ANTI-CONCEPTUS VACCINES
PLACENTA-SPECIFIC ANTIGENS/structural antigens
Forma a 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.
Placental antigen PP-5,when animal is actively immunized with human PP-5 and a
substantial reduction in fertility was shown

49. HORMONAL PLACENTAL ANTIGENS
Production or function of hCG can be inhibited immunologically, the
corpus luteum would regress
Type 1- 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)
Type 2- developed with support from the WHO Task Force on Vaccines
for Fertility Regulation, is based on a portion (carboxyterminal
peptide) 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

50. Conclusion
• From a global standpoint, there is clearly a desire and need for more
contraceptive options
• Couples desire more choices for fertility control as unplanned
pregnancies continue to occur at alarming rates
• Paucity of research in male hormonal contraceptive control
• Government and not-for-profit sponsors are needed to devote
necessary resources for long-term efficacy studies of newer molecules

51. THANK YOU