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Oral & Other Forms of Contraception

Oral & Other Forms of Contraception

Oral & other forms of contraception

Objectives:

Perceive the different contraceptive utilities available. Classify them according to their site and mechanism of action. Justify the existing hormonal contraceptives present. Compare between the types of oral contraceptives pills with respect to mechanism of action, formulations, indications, adverse effects, contraindications and possible interactions. Hint on characteristics & efficacies of other hormonal modalities.

Done by: Editing file

Ahmad Alkhiary, Abdulaziz Alhammad, Raghda Alqassim, Khalid Aburas, Atheer Alnashwan

Revised by: Raghda Alqassim, Qusay Ajlan

Drug’s name | Doctors’ notes | Important | Extra Mind Map

Oral Contraceptive Pills

Combined pills Mini pills (pop) Morning-after (coc) pills

Contain both or Contain Contain only a Each one alone & progestin (high dose) progestin (97% effective) OR (100% effective) +

Estrogens + , and

Systemic androgenic NO systemic androgenic effect: effect Norethindrone, Norgestimate, Drospirenone and and Desogestrel

Nice introduction ^^ 4:20 min Definition

Conception Contraception

Fusion of the sperm & ovum to produce preventing the fusion between the a new organism. sperm and ovum to occur.

Contraception can be achieved by interfering with :

Normal process of Implantation Preventing sperm from fertilizing the ovum

HORMONAL IUD (Copper T) THERAPY : يسمى لولب، طريقته إن النحاس يقتل الحيوانات المنوية

- Oral Interruption by a Killing the sperm : Contraceptive barrier : pills (OCP)

- Contraceptive • Condoms Spermicidal: • Cervical caps ( يجلس لمدة أطول) Patches - Vaginal rings Pic • Jells (Diaphragms) - Injectable • Foams • Thin films - IUD (intra- uterine devise)

(with ) Pic Quick physiological revision

5 min

13 13 min Oral Contraceptive Pills

Oral Contraceptive Pills

According to composition & intent of use; OC are divided into three types

Combined pills Mini pills (pop) Morning-after (coc) pills

Contain Contain only a Contain both hormones or Each one alone (high dose) estrogen & progestin progestin OR (100% effective) (97% effective) Mifepristone + Misoprostol

فعاليته أقل من الكومبايند بشوي من اسمهم )كومبايند( يعني مكونة من Induce إستروجين وبروجستن

Combined Pills (COC)

Progestins Estrogen

1. Norethindrone Ethinyl or 2. Levonorgestrel () mestranol [a “” 3. Medroxyprogesterone acetate converted to ethynyl estradiol]  Not used anymore because it has systemic androgenic effects:  Currently concentration , , weight gain (weight used is very low to gain in all types of oral contraceptives) minimize estrogen hazards

1. Norgestimate MCQ: 2. Desogestrel Which of the following is devoid from systemic androgenic effect? اإلجابة هي واحد من الثالثة Drospirenone .3  Currently used because it has no systemic androgenic effects ألن أكيد مافيش ستّة حتبقى عايزة يطلع لها أكني وشعر Combined Pills (COC)

1. Inhibit Ovulation by Suppressing The Release Of Gonadotrophins (FSH & LH)  no action on the ovary  ovulation is prevented. (the main and most

في الحمل يزيد عندها اإلستروجين والبروجستيرون بينما FSH & LH يق ّلون عشان (important mechanism ما يصير فيه ovulation )بسبب ve feedback I- .. هنا نفس الحالة

2. Inhibit IMPLANTATION by causing abnormal contraction of the fallopian of action of tubes & uterine musculature  ovum will be expelled rather than implanted.

3. Increase viscosity of the cervical mucus making it so viscous  no Mech. تذكروا في الluteal phase تتغير ال viscosity of cervical mucus )تحت تأثير البروجستيرون .sperm pass غالبًا( ألن وقت الليوتيال فيس مو مناسب للسبيرم يدخل ويسوي فرتليزيشن! هنا نفس الميكانزم صارت. 4. Abnormal transport time through the fallopian tubes .

❖ Monthly Pills: ❖ Seasonal Pills:

o Pills are better taken at the same o Are known as Continuous / Extended cycle  Cover 91 days الهدف هو المحافظة على تركيز ثابت في الدم .time of day schedule.  cover 3 months, each 3 months o For 21 days: starting on day 5 / she will have 1 period  she will have ending at day 26. (26-5=21dys) 4periods\year instead of 12 p\year. o This is followed by a 7 day pill free o Taken continuously for 84 days , and then a break for 7 days. period (7 days without pills) o Has very low doses of both يعني تبدأ المرأة تاخذها أثناء الدورة الشهرية حقتها )اليوم الخامس(، ضروري تبدأ estrogens and progestins قبل ما تخلص دورتها ألن مفعول الدواء ما راح يطلع إال بعد ٧ أيام، تستمر تاخذها لمدة ٢١ يوم، بعدين توقف لمدة ٧ أيام.. في هذي ال٧ أيام، راح Benefit: It lessens menstrual periods ❖ تنزل عليها الدورة ثانية.. وبعدها تأخذ الدواء وهكذا كل شهر ❖ To improve compliance: we use to 4 times a year  useful in those a formulation of 28 pills. who have pre - menstrual or menstrual disorders, and in o The first 21 pills are of perimenopausal women with multiphasic formulation vasomotor symptoms on pill free days يعني هي تنظم الدورة، ألن المرأة الmedicated) pre & peri-menopausal)

تصير الدورة متخبصة عندها وكل شوي تجي وتضايقها Methods of administration of Methods o Followed by the last 7 placebo Useful in those who have pain from and can prevent pills (dummy pills) (so in this case there is no break , but the last 7 pills have no effect) migrains during period. Disadvantages: Higher incidence of ❖ في هذا النوع بيصير أخذ الحبوب شهريًا بدون أي أيام بريك زي اللي قبل، واحد breakthrough bleeding & spotting من األهداف إنه يصير أخذ الحبّة بموعد ثابت ومنظم طوال الشهر، وتصير الوحدة

ما تضيّع متى أخذتها وتلخبط موعد أخذ األدوية.

التفاصيل هذي التفاصيل عن راحأسألكم عن .Helpful video during early use ما قالت الدكتورة قالت ما

Currently, the formulation of monthly pills are improved to mimic the natural on going changes in hormonal profile. ❖ Accordingly we have now the phase formulations: كلهم ثابتين (Monophasic  (a fixed amount of estrogen & progestin .1 2. Biphasic (2 doses) (a fixed amount of estrogen, while the amount of اإلستروجين ثابت، البروجستيرون متغير (progestin increases stepwise in the second half of the cycle 3. Triphasic (3 doses) (amount of estrogen; fixed or variable & amount of

اإلستروجين ثابت أو متغير ، البروجستيرون متغير .(progestin increases stepwise in 3 phases Phase Formulation Phase هنا لما نستخدم اإلستروجين، نستخدمه على شكل Ethinyl estradiol ولما نستخدم البروجستيرون، nd rd نستخدم وحدة من الformulas المذكورة في الساليد السابق (and 3 mimics the real cycle 2) Combined Pills (COC) (cont.)

الجدول بس لتوضيح المفهوم حق المونو والباي والترايفيزك، :All you have to know from the tables ❖ ال تضيعون وقتكم عليه the Biphasic and Triphasic tablets have a stepwise increase in the ✓ + نالحظ إن األستروجين غالبًا قليل عشان نقللل أعراضه (concentration of Progestin (twice in Biphasic , and 3 times in Triphasic الجانبية

Estrogen Related Progestin Related:

1. and breast tenderness. 1. Nausea, & 2. Headache . 2. Slightly higher failure rate. ”الكلف” ويطلع أثناء الحمل ويسمى , of mood .3 “كلف الحمل” )البقع السوداء(  Skin Pigmentation .3 4. Impaired glucose tolerance 4. Menstrual irregularities () 5. Weight gain

ADRs 5.  incidence of breast, vaginal & Progestin causes weight gain, why use it with obese عشان كذا يفضل إنه يؤخذ مع women? Estrogen causes increased risk of developing البروجستن عشان يقلل الكانسر إفكت .cervical cancer 6. Cardiovascular: (major concern) cancer in obese women up to 2-4 times a. Thromboembolism 6. Hirsutism . b. Hypertension 7. Masculinization (Norethindrone) 7.  frequency of gall bladder disease 8. Ectopic . ❖ Contraindications of Estrogen containing pills:

1. Thrombophlebitis / thromboembolic disorders (Estrogens enhance the coagulability of blood) 2. CHF or other causes of edema 3. of undiagnosed etiology (fear of neoplasm) 4. Known or suspected pregnancy (it may cause ) 5. Known or suspected , or estrogen-dependent neoplasms

6. Impaired hepatic functions C.I 7. Dyslipidemia*, diabetes, hypertension, migraine. (* bc of increase triglyceride by estrogen, Estrogens decrease hepatic oxidation of adipose lipid to and increase synthesis of triglycerides.) You use Mini pills (which contain only progestin) with 4 types of females: ✓ Lactating mothers (nursing women) ✓ Obese ✓ Smokers. ✓ Females > 35 years. ADRs Uses P.K MOA Drug

o o o o o Combined pills (COC) interactions Norethindrone acne It hypertension, cancer, smokers over the age of Alternative I.M injections e.g. same time Contraceptives therefore, The main effect is has has Medroxyprogesterone , systemic hirsutism Medications that Medications altered in altered Medications that cause that Medications contraceptive Medications that are that Medications no fertilization , when لهم أريح شهور أريح لهم allyear round. , androgenic containing containing onlya progestin s Combined Pills (COC Combined Levonorgestrel , and Contain estrogen estrogen is contraindicated by COC by toxicity increasing cervical mucus medroxyprogesterone acetate ٣ clearance ( clearance كل Mini weight weight gain IM only a only . inection failure effect  pills (POP) progestin ال COC & ياخذون : .  )

، ت o ق و ل ا (97% effective) (97%

س Norgestimate effect Has ف ن ب hould

ا ) ي ً م و metabolism of , (cont.) 35  ي e.g

(during e.g.: e.g.:  Microsomal Microsomal No Microsomal Microsomal Enzyme Inducers so so no sperm penetration and ة normal ع catabolism catabolism of oral e.g.: e.g.: ر ) Antibiotics that Antibiotics interfere with .: Clearance Clearance Impairing absorption ج be be taken CYTP ل CYTP السابق systemic androgenic Acetaminophen ا ب

150 ن Desogestrel ( و Warfarin e.g.  م GI flora flora GI ز breast breast feeding الساليد e.g.: e.g.: ت ل  Theophylline ي mg every 

 ا 450 م ,  450 Rifampin

في its  warfarin toxicity)warfarin و Drospirenone oral contraceptive oral  أ everyday

Ampicillin toxicity ن its action , قلناهم و ,   Phenobarbitone س Inhibitors Inducers Cyclosporine ن ي

اللي نفس اللي in their ن  ك , contraceptive contraceptive م inhibitors م absorption absorption

3 ي ل ل months. ا

, س , toxicity the the ا ن ل : ل :

: ي , ذ   & ه  , Morning-after pills

❖ Contraception on instantaneous demand, 2ndry to unprotected sexual intercourse. ❖ When desirability for avoiding pregnancy is obvious: ( and post-coital (after the sexual intercourse) contraception) o Unsuccessful withdrawal before ejaculation. o Torn, leaking condom.

Indications o Missed pills.

جاء سؤال السنة الماضية عن هذي النقطة .o Exposure to teratogen e.g live vaccine

اغتصاب o Rape • They may cause nausea & vomiting  we may add anti-emetic with it. Method of Timing of 1st dose composition Reported efficacy administration after intercourse Ethinyl estradiol + 2 tablets twice with 0- 72hrs 75% Levonorgestrel. 12 hrs in between

High-dose only Twice daily 0- 72hrs 75 - 85% Ethinyl estradiol For 5 days

High dose only Twice daily 0- 72hrs 70 – 75% levonorgestrel For 5 days Mifepristone1 ± Misoprostol2 A single dose 0- 120 hrs 85 - 100% (Used to induce abortion)

1 Mifepristone is a synthetic with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. 2 Misoprostol is a E1 (PGE1) analogue. Summary-1 estrogens Progestin’s

Has systemic androgenic effect; acne, hirsutism, weight gain. Has no systemic androgenic effect Ethinyl estradiol or Currently: mestranol (a prodrug • Norrthindrone • Norgestimate. converted to ethinyl • Levonorgestrel (norgestrel) • Desogestrel estradiol) • Medroxyprogestrone acetate • Drospirenone. Mini pills (POP), Morning-after pills Combined pills (COC) contains only a Contain both hormones or each Contains estrogen & progestin

Drug progestin (97% one alone (high dose) or (100% effective) effective) Mifepristone ± misoprostol) 1. Inhibits ovulation by suppressing the Emergency contraception, post coital Contains only release of gonadotrophins (FSH & LH) contraception. progestin > as > no action on the ovary > ovulation is Contraception of instantaneous norethindrone or prevented. demand, 2ry to unprotected sexual desogestrel…. 2. Inhibits implantation by causing intercourse. abnormal contraction of the fallopian

of action of The main effect is tubes and uterine musculature > ovum composition increase cervical will be expelled rather than implanted. mucus, so no sperm 3. Increase viscosity of the cervical mucus Ethinyl High dose penetration and estadiol + only

Mech. making it so viscous > no sperm pass. therefore, no 4. Abnormal transport time through the levonorge ethinyl fertilization.

fallopian tubes. strel estadiol

Mifepristone ± misoprostol Pills are better taken same time of day. For 21 Should be taken days starting on day 5 ending at day 26. this every day, the same is followed by 7 day pill free period. time, all year round. I.M injection e.g. - P.K TO IMPROVE COMPLIANCE: medroxy The first 21 pills are of multiphasic formulation acetate followed by the last 7 pills are actually 150 mg every 3 placebo. months. When desirability for avoiding Are alternative when pregnancy in obvious: estrogen is -unsuccessful withdrawal before contraindicated (e.g.; ejaculation. during breast Seasonal pills monthly pills -torn, leaking condom. feeding, -missed pills. hypertension, -exposure to teratogen e.g. live Indications cancer, smokers vaccine. over the age of 35) -rape. Combined pills (COC)

Drug Seasonal pills Monthly pills - Knows as continuous/extended cycle > cover 91 days Currently, their formulation is improved to mimic the schedule taken continuously for 84 days, break for 7 days. natural on going changes in hormonal profile. - Has very low doses of both estrogens and progestin's.

benefit disadvantages Accordingly we have now the phase formulations:

1-monophasic 2-biphasic 3-triphasic

of action of It lessens menstrual period Higher incidence of to 4 times a year > useful in breakthrough A fixed 2 doses> a fixed 3 doses>amount of those who have pre- bleeding and spotting amount of amount of estrogen estrogen; fixed or menestrual disorders, and during early use. estrogen and while amount of variable and amount proges tin increases Mech. in peri-menopausal women progestin. of progestin stepwise in the second with vasomotor symptoms half of the cycle. increases stepwise in 3 phases. Summary-2

Combined pills (COC) (cont.)

1. Nausea and breast tenderness. 2. Headache. 3. Increase skin pigmentation. Estrogen 4. Impair glucose tolerance (hyperglycemia) related 5. Increase incidence of breast, vaginal and cervical cancer. 6. CVS- major concern. (thromboembolism and hypertension) 7. Increase frequency of gall bladder disease.

1. Nausea, vomiting and headache.

ADRs 2. Slightly higher failure rate. 3. Fatigue, depression of mood. 4. Menstrual irregularities. Progestin 5. Weight gain. related 6. Hirsutism. 7. Masculinization (Norethindrone) 8. .

1. Thrombophlebitis / thromboembolic disorders. 2. CHF or other causes of edema. 3. Vaginal bleeding of undiagnosed etiology. 4. Known or suspected breast cancer, or estrogen-dependent neoplasms. Of estrogen 5. Impaired hepatic functions. containing 6. Dyslipidemia, diabetes, hypertension, migraine……. pills 7. Lactating mothers – use progestin – only pills (mini pills) N.B. obese females, smokers, females > 35 years. Better given progestin

contraindication only pills.

Combined pills (COC) - interactions

Medications that is Medications that cause Medications that altered in clearance contraceptive failure increase COC toxicity by COC

1-Impairing 2-CYT P450 CYT P450 inhibitors absorption inducers

• Antibiotics that interfere with normal GI flora > decrease Microsomal enzyme Increase in their toxicity. absorption > decrease its inhibitors; decrease of OC > Warfarin, cyclosporine, bioavailability. increase toxicity e.g.: theophyline. • Microsomal enzyme inducers > acetaminophen, increase catabolism of OC e.g.: erythromycin. phenytoin, phenobarbitone, rifampin. MCQs

1- The toxicity of combined pills can be 7- Which of the following can act as a single increased by: dose postcoital contraceptive: A. Sildenafil A. Clomiphene citrate B. CYT P450 inducers B. Ethynyl estradiol C. CYT P450 inhibitors C. Norgestimate D. D. Mifepristone

2- In combined pills, which of the following is 8- In which of the following forms of oral a major related to estrogen? contraception, pills are taken continuously A. Nausea without interruption: B. Cardiovascular disease A. Combinedpill C. Breast tenderness B. Phased pill D. Headache C. Minipill D. Both B & C 3- A women had an unprotected sexual intercourse, she remembered after 4 days that 9- Which side effect of the oral contraceptive she didn’t take any oral contraceptive, what’s subsides after 3–4 cycles of continued use: the best drug for her situation? A. Glucose intolerance A. Ethinyl estadiol + Levonorgestrel. B. Rise in blood pressure B. High-dose Ethinyl estadiol. C. Headache C. Misoprostol D. Fluid retention D. High dose levonorgestrel 10- Concurrent use of the following drug is 4- A breast feeding women was taking oral likely to cause failure of oral contraception: contraceptives, after few months she noticed A. Isoniazid some hair growing on her face and acne, B. which one of the following drugs would cause C. her symptoms? D. Propranolol A. Norethindrone B. Drospirenone 11- Actions of progesterone include the C. Norgestimate following except: D. Desogestrel A. Rise in body temperature B. Endometrial proliferation 5- Select the drug which administered orally C. Proliferation of acini in mammary gland causes cervical ripening in pregnant women D. Suppression of mediated immunity to facilitate surgical abortion or induction of labour: 12- Which of the following is devoid from A. Mifepristone systemic androgenic effect? B. A. Norethindrone C. Levonorgestrel B. Norgestrel D. Natural progesterone C. Medroxyprogesterone acetate D. Norgestimate 6- Mifepristone possesses the following activities: A. Potent anti-progestin + weak androgenic B. Potent anti-progestin + weak C. Potent anti-estrogenic + weak antiprogestin D. Potent anti-estrogenic + weak

Answers: 1-C 2-B 3-C 4-A 5-A 6-B 7-D 8-C 9-C 10-B 11-B 12-D Thank you for checking our team!

Sources: 1. 435’s slides. 2. Basic & Clinical Pharmacology by Katzung, chapter 40, 12th edition.

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