oral contraceptives

1. Oral
Contraceptives
By: Devanshi Bavishi
M.Pharm Sem 2
Advanced Pharmacology II

2. Contraception
– It is the interception in the birth process at any stage ranging from ovulation to
ovum implantation.
– It should not only be safe but also provide reversible suppression of fertility.
– Also termed as “ Birth Control”

3. Methods Of Contraceptiom

4. Male
Contraception

5. Need for male contraception
– More recognition for the need of shared contraceptive responsibility.
– Reduce the burden traditionally placed almost exclusively on the female
partner
– Specially in cases where female cannot adapt for contraception due to medical
or surgical problems

7. Natural methods
1. Abstinence
2.Coitus Interruptus: failure rate 22/HWY
– Drawbacks: Only for educated and responsible couples
– Programmed Sex

8. Condoms
– Most widely used barrier
– Made up of fine sheath
– Most are latex
– Also available in polyurethane,
– silicone, and lambskin
– Desensitizing condoms with lubricant featuring benzocaine,helps prolong sexual
pleasure and aids in prevention of premature ejaculation
– Spermicidally lubricated condoms (failure-1%)

9. Cont..
Advantages
– Available widely without a
prescription
– Inexpensive/ free govt supply
(Nirodh)
– Latex condoms protect against STIs
– Helpful in case of intolerance to
IUCD, Oral pills or in
– case of premature ejaculation
Disadvantages
– slippage/breakage during
intercourse (failure rate- 4-15%)
– Latex allergy with latex condoms
(Medical Eligibility Criteria category
3)
– May reduce sexual pleasure
– Lambskin condoms do not protect
against STIs

10. Terminal Methods
– Vasectomy
– Vas Occlusion Method

11. Vasectomy
– A surgical procedure to resect / close the vas deferens (the tubes that carry
sperm to the penis)
– Conventional vasectomy – one or two incisions are made in the scrotum to
reach the vas deferens
– No-scalpel vasectomy – a puncture is made in the scrotum

13. Cont..
Advantages
– No routine contraceptive required
– No interference with intercourse
– No significant long-term side effects
– Simple procedure
– Less invasive and more cost-effective
than tubal ligation 6. Allows the male
partner to assume some
responsibility for birth control
Disadvantages
– Difficult to have reversal
– Post-sterilization regret
– Short-term surgery-related
complications: pain and swelling;
vasovagal reaction; infection
– No protection against STIs
– Not effective immediately. Additional
methods required for 2.5-3 months till
follow-up sperm analysis shows no sperm

14. Vas Occlusion
– Blocks sperm transport in the vas deferens
– Alternative to vasectomy and possible hormonal contraceptive treatments that
are currently being researched.
– Potential methods include clips, plugs, valves, and other devices.

15. R.I.S.U.G
– Reversible Inhibition of Sperm Under Guidance (RISUG)
– similar to VASALGEL under animal trials in USA

16. RISUG- Mechanism of action
– Non-hormonal injectable contraceptive composed of SMA (styrene maleic
anhydride) mixed with DMSO (solvent dimethylsulfoxide)
– Partially blocks the vasa deferentia and destroys the sperm
– Differential charge from the gel ruptures the sperm’s cell membrane

18. How Reversal?
– Reversals by multiple injection of dimethyl sulfoxide or sodium bicarbonate –
takes several months
– Reversal proven in monkeys after 1½ years of use, all had normal sperm count
within 3 months of reversal.
– Not yet (formally) tested in men

19. SMART RISUG
– Iron oxide and copper particles added to the original compound, giving it
magnetic properties and the name “Smart” RISUG.
– The polymer location can be externally controlled with magnetic field, the
polymer can change location inside the body to maximize sterility or can be
removed to restore fertility.
– Iron oxide and copper particles added to the original compound, giving it
magnetic properties and the name “Smart” RISUG.
– The polymer location can be externally controlled with magnetic field, the
polymer can change location inside the body to maximize sterility or can be
removed to restore fertility.

20. Cont..
– The addition of metal ions also increases the effectiveness of the spermicide.
– The low frequency electromagnetic field disintegrates the sperm cell membrane
in the head region, making the sperm infertile.
– safety of Smart RISUG is still being investigated.

21. Intra Vas Devices
– The IVD, is a flexible, hollow, silicone plug that is inserted into the vas deferens tubes
to block sperm transport.
– IVD insertion will involve accessing the vas deferens tubes much like during a
vasectomy, except rather than cutting and cauterizing the tubes, thereby
permanently damaging them, only a small opening is made in each tube, to insert
two silicone plugs.
– The tiny opening is expected to heal completely and rapidly. It is anticipated that the
IVD can later be removed in a similar procedure to its insertion, reestablishing
sperm flow.
– The IVD has the potential to become an attractive alternative to standard
vasectomy…

22. 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.

23. Injectable Vas devices
– The polymer is injected directly into the vasa deferentia and solidifies forming a
flexible plug
– Less than 30 minutes under local anesthesia.
– Easier to reverse (recovery within 2 to 4 years after the reversal procedure)

24. Non hormonal Male pill-Gossypol
– Cotton seed derivative
– Causes azoospermia and severe oligospermia
– Toxic(Hypokalemic Paralysis1%)
– Use for 6 months leads to complete sterility

25. Adjudin “The male Patch”
– Non-hormonal male contraceptive
– Non-toxic lonidamine Analog (2,4dichlorobenzyl1Hydroxy-indazole
carbohydrazide)
– Disrupts cellular bridges between spermatids and Sertoli cells
– Blocks the maturation of sperm in the testes without affecting testosterone
production

26. Hormonal Contraception
– Supra-physiological dose of testosterone suppresses testicular production of
Testosterone
– Halts spermatogenesis
– May include a progestin for faster, complete suppression
– Oral formulations
– Depot injections
– Implants
– Transdermal gels and patches

27. Testosterone Enanthate
– 200 mg weekly injections used in a multicentric study (1986-1990)
– All men achieved azoospermia & were able to sustain safe, reversible
contraception for atleast 12 months (1990 WHO Task Force)
– But it required high doses of testosterone, affecting other organs like prostate,
Liver (HDL decreased) , Bone & Muscles

28. Progestrone + Testosterone
– Oral progestrone inhibits spermatogenesis by inhibiting
gonadotrophins and physiological replacement of testosterone is
required for sexual functions
– Levonorgestrol pill + Testosterone INJ.( Anawalt et al 2005) was
rapid & effective to inhibit spermatogenesis but decreased HDL
levels & increased risk of coronary heart disease

29. Antiandrogenic progesterone pill
– Anti androgenic progestrone cyproterone acetate
in low doses (12.5 mg daily) and injectable
testosterone 100mg per week for 16 weeks has
known to cause complete azoospermia in 8-10
weeks with no biochemical ill effects.

30. Gendarussa
– First non hormonal 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…

31. 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.

32. CatSper Blocker
– Catsper is a gene for calcium ion channels in various
parts of the body including the sperm tail.
– Sperm rely on calcium ions in sperm-tail for mobility and
fertilization In future, it can be a target for drugs to
immobilise sperms

33. Male Vaccines …
– Scientists are trying to isolate, identify, and
produce Anti sperm surface antigens which will
hinder sperm – egg without side effects.

34. Female Contraceptives

35. Menstural Cycle
– Menstruation is the visible
manifestation of cyclic physiologic
uterine bleeding due to the
shedding of the endometrium(the
innermost layer of the uterus).This
is due to invisible interplay of
hormones mainly through the
hypothalamic-pituitary-ovarian
axis.
Hypothalamic –Pitutary-Ovarian Axis

36. A menstrual cycle consists of uterine and ovarian changes
which occur side by side. A uterine change consists of three
phase i.e bleeding phase, proliferative phase and secretory
phase whereas ovarian phase consists of menstrual phase,
follicular phase(corresponds to proliferative phase)and luteal
phase(corresponds to secretory phase)

38. Non Hormonal Methods
– Natural Method
– Barrier Method
– Intrautrine devices(IUDs)
– Permenant

40. Classification
A. ORAL CONTRACEPTIVES (OCs)
(I) COMBINATION PILLS: Containing a combination of estrogen + progestins in varying
amounts or in phased regimens (MONOSHA SIC, BIPHASIC or TRIPHASIC).
ii) MINI PILLS (PROGESTIN-ONLY PILLS): Containing progesterone preparation alone.
iii) POST COITAL (MORNING AFTER) PILLS or Emergency contraceptive pill
iv) CENTCHROMAN: Non-hormonal estrogen receptor antagonist.
B. INJECTABLE CONTRACEPTIVES
i) DEPOT MEDROXYPROGESTERONE ACETATE (DMPA)
ii) ESTRADIOL VALERATE + 17-HYDROXYPROGESTERONE CAPROATE
iii)ESTRADIOL CYPIONATE MEDROXYPROGESTERONE ACETATE

41. Cont…
C. RECENT CONTRACEPTIVE METHODS
i) LEVONORGESTREL subcutaneous implant
ii) LEVONORGESTREL intrauterine inserts
D. HORMONAL CONTRACEPTION IN MALES
i) TESTOSTERONE UNDECANOATE
ii)TESTOSTERONE UNDECANOATE+ MEDROXYPROGESTERONE ACETATE (DMPA)
iii) GOSSYPOL

42. General Mechanism

43. Combined Pill:
(combinations of an oestrogen with a
progestogen)
– The oestrogen in most combined preparations: (second-generation pills)
ethinylestradiol, although a few preparations contain mestranol instead.
– The progestogen may be norethisterone, levonorgestrel, ethynodiol, or-in
third- generation pills- desogestrel or gestodene, which are more potent, have
less androgenic action and cause less change in lipoprotein metabolism, but
which probably cause a greater risk of thromboembolism than do second-
generation preparations.

44. Cont…
– The oestrogen content is generally 20-50μg of ethinylestradiol or its equivalent,
and a preparation is chosen with the lowest oestrogen and progestogen content
that is well tolerated and gives good cycle control in the individual woman.
– This combined pill is taken for 21 consecutive days followed by 7 pill-free days,
which causes a withdrawal bleed. Normal cycles of menstruation usually
commence fairly soon after discontinuing treatment.

45. Mechanism Of Action
– Oestrogen inhibits secretion of FSH via negative feedback on the anterior
pituitary, and thus suppresses development of the ovarian follicle
– Progestogen inhibits secretion of LH and thus prevents ovulation; it also makes
the cervical mucus less suitable for the passage of sperm
– Oestrogen and progestogen act in concert to alter the endometrium in such a
way as to discourage implantation. They may also interfere with the
coordinated contractions of cervix, uterus and fallopian tubes that facilitate
fertilisation and implantation.

46. Adverse Effects
– Weight gain, owing to fluid retention or an anabolic effect, or both
– Mild nausea, flushing, dizziness, depression or irritability
– Skin changes (e.g. acne and/or an increase in pigmentation)
– Amenorrhoea of variable duration on cessation of taking the pill.

47. Monophasic Pills
– Monophasic pills have a constant dose of both estrogen (ethinyl estradiol) and
progestin (levonorgestrel) in each of the hormonally active pills throughout the
entire cycle (21 days of ingesting active pills)
– Side effects : mood changes, including breakthrough bleeding, spotting and
amenorrhea that can result from fluctuating hormone levels in the body.
– Microgestin, Modicon, Nexon, Nelova, Nordette, Norinyl. Ortho Cept, Ortho-Cyclen,
Ortho-Novum, Ovcon, Ovral, Yasmin
– Low dose of estrogen (20 mcg)
– Regular dose 30-35
– High dose 50 mcg

48. Cont…
Biphasic Pills
– Biphasic pills have a fixed dose of
estrogen for 21 days but with increasing
doses of progesterone during two and
uterine successive phases, i.e., from the
day 1-10 and 11-21. Next 7 days are pill
free days
– For example: Ethinyl estradiol (35 ug) +
Norethindrone (0.5 mg). A pack of ten
tablets from day 1 to day 10. Then,
Ethinyl estradiol (35 ug) + Norethindrone
(1 mg). A pack of 11 tablets from day 11
to day 21. These are not marketed in
India.
Triphasic Pills
– Triphasic pills provide a bit higher
dose of estrogen at near midcycle
but increasing doses of
progesterone for three successive
phases, i.e., for days 1 to 6, 7 to 11
and 12-21 days. This is then
followed by a gap of 7 days as pill
free period.

49. Mini Pills Or
Progesterone only Pills
– progestin-only pills are given to those cases estrogen is contraindicated. Pills are
prescribed soon after delivery and continued without intruption .
Examples: Norethindrone 350 ug or Norgestrel 75.hese are not marketed in
India.
– Mechanism of Action: Progestins place the endometrium prematurely to the
secretory phase and increase the viscosity of cervical mucus making the
environment unfavourable to sperm penetration.
– Side Effects: These are less effective. Side effects include acne, hirsutism and
amenorrhoea for more than 45 to 60 days

50. Pharmacokinetics
– Combined and progestogen-only oral contraceptives are metabolised by hepatic
cytochrome P450 enzymes.
– Because the minimum effective dose of oestrogen is used (in order to avoid
excess risk of thromboembolism), any increase in its clearance may result in
contraceptive failure, and indeed enzyme-inducing drugs can have this effect
not only for combined but also for progesterone-only pills.
– Such drugs include rifampicin and rifabutin, as well as carbamazepine,
phenytoin, griseofulvin and others.

51. Post Coital Pills
– High dose estrogen and/or high dose progestin.
– Two tablets of progestin levonorgestrel (750 µg each)[NORLEVO]. The first
tablet must be taken as soon as possible (within 48 hrs of the coitus) and the
second tablet taken after 12 hrs.
– Ethinyl estradiol (50 µg each tablet) + Levonorgestrel (250 µg each
tablet)[OVRAL]. Two such tablets are to be taken within 72 hrs of unprotected
coitus and next 2 tablets after 12 hrs.

52. Cont…
– Mifepristone (antiprogestine) 600 mg single dose taken within 72 hrs of
unprotected intercourse.
– iPILL (Levonorgestrel 1.5 mg ;single tab)
– To be taken within 72 hrs.

53. Centchroman (ormeloxifene)
– Nonsteroidal estrogen antagonist
– Developed at CDRI India.
– Oral contraceptive under the brand name SAHELI.
– Dose 30 mg
– Taken twice in a week for first 3 months and then once a week subsequently.
– Suppressed proliferative stage of endometrium.
– If the menstrual cycle is prolonged for more than 15 days, pregnancy should be
ruled out.

54. Injectable contraceptives
– Depot medroxyprogesterone acetate (DMPA; Depo Provera)
– Mode of action: same as minipills
– Longer acting progesterone derivative
– Injected i.m.
– Dose 150 mg every 3 months
– Useful in those
– where compliance is a problem,patients having heavy menstrual bleeding
in those for whom estrogens are contraindicated

55. Transdermal Contraception
Works trans-dermally by:
1. Combination of progestin & estrogen
2. Slowly releasing
3. Through skin
Types:-
1. Patch
2. Spray-on
3. Gel 49

56. Cont..
– Transdermal contraceptive patch ‘OrthoEvra’ was approved by US FDA in 1992.
– Sites: Buttocks, Upper outer arm Lower abdomen, back, upper torso.

57. Cont..
– 3-patch system
– Apply 1 patch each week for 3 weeks
– Apply each patch the same day of the week
– 1 week is patch-free

58. Spray-On Contraception
– Nestorone - Metered Dose Transdermal System (MDTS)
– In phase I Clinical trail as:
– Absorbed instantaneously
– MDTS® daily skin spray formulations
– Hormone collects as reservoir with in the skin and slowly diffuses into the blood
stream

59. Complications
– Leg vein thrombosis, Pulmonary thrombosis with older pills
– Coronary, cerebral thrombosis resulting in MI, Stroke not seen with low dose
pills
– Rise in BP
– Minor increase in breast cancer
– Benign hepatomas Gall stones

60. Drug Interaction
– Contraception failure with enzyme inducers like rifampin, phenytoin,
carbamazepine
– Also with tetracycline, ampicillin Wise to increase the dose or use alternative
methods

61. What if Missed??