Hormonal%20contraception Treatment

Combination Oral Contraceptives (COCs)

• COCs consist of tablets containing both an estrogen and a progestin; most widely used formulations
• Low-dose COCs that contain 20-35 mcg of estrogen are associated with a lower risk of venous thromboembolism (VTE) and have generally replaced older oral contraceptives (OCs) containing ≥50 mcg
• Risk of ischemic stroke is high with COCs containing >35 mcg of Ethinyl estradiol 

Formulations

• Monophasic: Each tablet contains a fixed amount of estrogen and progestin
• Biphasic: Each tablet contains a fixed or variable amount of estrogen, while the amount of progestin increases in the 2nd half of the cycle
• Triphasic: The amount of estrogen may be fixed or variable, while the amount of progestin increases in 3 equal phases
• Quadriphasic: A higher dose of estrogen is delivered at the beginning of the cycle and ends with the lowest dose; progestin dose is varied also during the cycle

Uses

• Usual cycle: Hormonal pills taken for 3 weeks followed by a hormone-free week  
• Extended use: Hormonal pills taken for 12 weeks followed by a hormone-free week  
• Continuous use: Uninterrupted intake of hormonal pills without a hormone-free interval

Indications

• COCs are considered for any woman seeking a highly effective, reversible and coitally-independent method of contraception
• May be considered in women in whom estrogen is not contraindicated and who wish to take advantage of COC’s non-contraceptive benefits
  • Ethinyl estradiol and Norgestimate may be used in women ≥15 years old for treatment of moderate acne unresponsive to topical anti-acne medications
  • Ethinyl estradiol and Drospirenone may also be used for the treatment of premenstrual dysphoric disorder symptoms in women taking oral contraceptives

Actions

• Main mechanism is suppression of midcycle gonadotropin secretion that in turn inhibits ovulation
• Induce endometrial atrophy, stimulate production of viscous cervical mucus that impedes sperm transport and affect secretion and peristalsis within the fallopian tube interfering with ovum and sperm transport

Effects

• Combined OC is a highly effective method of contraception
  • Failure rates in the first year of use are 0.3% in perfect users (correct and consistent use according to directions) and 7% in typical users (actual use which includes either incorrect or inconsistent use)

Non-Contraceptive Benefits

• May decrease menstrual flow, dysmenorrhea, perimenopausal symptoms
• May improve acne, hirsutism and other signs of polycystic ovarian syndrome (PCOS)
• May decrease risk of colorectal cancer, endometrial cancer, ovarian cancer, fibroids, ectopic pregnancy, ovarian cyst, benign breast disease and premenstrual dysphoric disorder or premenstrual syndrome
• Regulates menstrual cycle and reduces risk of iron-deficiency anemia
• Increases bone density

Disadvantages

• Spotting during the first few cycles and with inconsistent use
• May suppress lactation and may cause decreased libido or anorgasmia
• Daily pill intake may be stressful
• Increased risk of cervical adenocarcinoma, but not squamous cell cervical cancer
• No protection against STI
• May cause hypertension in 1% of COC users but this is reversible 1-3 months after discontinuation
• Concomitant use of certain drugs, eg anticonvulsants, antiretroviral drugs, Rifampicin, may lower its effectiveness

Absolute Contraindications

• <6 weeks postpartum if breastfeeding
  • Use of a COC during breastfeeding may affect growth and development of the infant because of diminished quantity of breast milk, decreased duration of lactation, and infant’s exposure to steroids
• <21 days postpartum not breastfeeding with VTE risk factors 
• Smoker ≥35 years old (≥15 cigarettes/day)
  • Increased risk of CV events
• Obesity (BMI ≥40 kg/m²)
• CV disease
  • Cerebrovascular accident or stroke, ischemic heart disease, multiple risk factors for arterial disease
• Hypertension (systolic BP [SBP] ≥160 mmHg or diastolic BP [DBP] ≥100 mmHg)
  • May have an increased risk of stroke or MI
• Current or past history of VTE
  • <21 days postpartum not breastfeeding with other added VTE risk factors
• Valvular and congenital heart disease (complicated by pulmonary hypertension, atrial fibrillation, history of subacute bacterial endocarditis)
  • COC use may further increase the risk of arterial thrombosis
• Major surgery with prolonged immobilization
• Known thrombogenic mutations (eg Factor V Leiden)
• Migraine headache with focal neurological symptoms and aura at any age
• Gestational trophoblastic neoplasia (when hCG is abnormal)
• Current breast cancer
  • Breast cancer is a hormonally sensitive tumor, the prognosis may be worsened with COC use
• DM with retinopathy, nephropathy, neuropathy or DM >20 years in duration
• Severe decompensated liver cirrhosis
  • COC use may adversely affect women whose liver function is decreased
• Liver tumor (adenoma or hepatoma)
• Active viral hepatitis
• Raynaud’s disease
• Predisposed to hyperkalemia (renal insufficiency, hepatic dysfunction, adrenal insufficiency) especially COCs containing Drospirenone
• Systemic lupus erythematosus (SLE) diagnosis with positive antiphospholipid antibodies

Relative Contraindications

• Breastfeeding between 6 weeks-<6 months postpartum
• <21 days postpartum not breastfeeding without VTE risk factors
• Between 3 and 6 weeks postpartum not breastfeeding with VTE risk factors
• Smoker ≥35 years old (<15 cigarettes/day or stopped smoking <1 year ago)
• Obesity (BMI 35-39 kg/m²)
• Hypertension (SBP 140-159 mmHg, DBP 90-99 mmHg)
• VTE in a first-degree relative <45 years old
• Immobility (unrelated to surgery)
• Migraine headache without focal symptoms and aura in patients ≥35 years of age
• Past history of breast cancer with no evidence of disease for 5 years and no known gene mutations associated with breast cancer
• Currently symptomatic gallbladder disease medically treated
• Mildly compensated cirrhosis
• History of COC-related cholestasis
• Users of medications that may interfere with COC metabolism, eg anticonvulsants, Lamotrigine, Rifampicin, Rifabutin
• Known hyperlipidemias

Combination Injectable Contraception

• IM injection of contraceptive consisting of 5 mg Estradiol cypionate and 25 mg Medroxyprogesterone acetate given every month

Indications

• Injectable combination contraception may be considered for any woman seeking a highly effective, reversible and coitally-independent method of contraception
• Especially suited for women with difficulty complying with daily intake of pills, in those who want predictable monthly bleeding, or have enteric absorption problems

Action

• Causes contraception primarily by inhibition of ovulation

Effects

• Failure rates in the first year of use are 0.05% in perfect users and 3% in typical users

Absolute and Relative Contraindications

• Similar to COCs

Combination Transdermal Patch

Indications

• Medicated adhesive patch which contains Ethinyl estradiol and Norelgestromin 
• Transdermal patch may be considered for any woman seeking a highly effective, reversible and coitally-independent method of contraception
• It is especially suited for women seeking a method of contraception that does not demand daily attention

Actions

• Similar to COCs

Effects

• Efficacy may be influenced by body weight
  • Women ≥90 kg may find that the patch is less effective than in women of lesser body weight
• Failure rates in the first year of use are 0.3% in perfect users and 7% in typical users 
• Provides 60% more estrogen over a 21-day period than a 35-mcg Ethinyl estradiol COC and 3x more than the ring

Non-Contraceptive Benefits

• Cycle regulation has been shown to be comparable to COCs
• Non-contraceptive benefits seen in COCs are assumed to be the same in the transdermal patch though long-term studies are limited 

Disadvantages

• Similar to COCs
• Spotting and breakthrough bleeding in the 1st cycle but usually improve with time
• Must be removed and replaced weekly
  • Application site problems include detachment, skin irritation and pigment changes on the skin

Absolute and Relative Contraindications

• Similar to COCs

Combination Vaginal Ring

• A flexible ring placed inside the vagina that releases estrogen and progestin at a constant rate/day 
• The vaginal ring is left in place for 3 weeks and then removed on the 4th week wherein monthly bleeding will occur  
• Etonogestrel/ethinyl estradiol vaginal ring is replaced monthly while Segesterone acetate/ethinyl estradiol vaginal ring is reusable and can be cyclically repeated for 1 year  
  • US FDA-mandated postmarketing studies are required to further evaluate the risks of VTE and the effects of CYP3A-modulating drugs and tampon use on the pharmacokinetics of the Segesterone acetate/ethinyl estradiol vaginal ring 

Indications

• Vaginal ring may be considered for any woman seeking a highly effective, reversible and coitally-independent method of contraception
• Contraceptive ring is especially suited for women seeking a method of contraception that does not demand daily attention

Actions

• Similar to COCs

Effects

• Vaginal ring maintains a steady, low release rate for 35 days while in place and releases less estrogen every day at a more constant rate than patches or pills
  • Ovulation is suppressed for 35 days

• Failure rates in the first year of use are 0.3% in perfect users and 7% typical users

Non-Contraceptive Benefits

• Non-contraceptive benefits seen in COCs are assumed to be the same with vaginal ring use though long-term studies are limited
• Better withdrawal bleeding and spotting pattern than COCs
• Less irregular bleeding in the 1st cycle and continues to decrease throughout the following cycles
• Better compliance in women

Disadvantages

• Withdrawal bleeding may continue beyond the ring-free interval
• Women may feel uncomfortable in placing/removing the ring

Absolute and Relative Contraindications

• Similar to COCs
• Uterovaginal prolapse and vaginal stenosis are considered relative contraindications if they prevent retention of the ring

Progestin-only Pills (POPs)

• Also known as “mini-pills”; contain low doses of progestins (eg Desogestrel, Drospirenone, Ethynodiol diacetate, Levonorgestrel, Lynestrenol, Norethisterone or Norgestrel)

Indications

• POPs are considered in any woman seeking a highly effective, reversible and coitally-independent method of contraception
• May be considered in women in whom estrogen is contraindicated
  • Eg women who smoke, women who experience migraine headaches with neurological symptoms, history of thrombosis, with SLE, recently postpartum or those who breastfeed

Actions

• The chief mechanism of action is an increase in the viscosity of cervical mucus which prevents sperm entry
• It causes thinning and atrophy of the endometrium
• POPs also reduce the volume of mucus, alter molecular structure, and impair sperm motility and penetration along with partial suppression of ovulation

Effects

• The failure rates in the first year of use are approximately 0.3% in perfect users and 7% in typical users

Non-Contraceptive Benefits

• May decrease menstrual flow and up to 10% of users develop amenorrhea
• Premenstrual symptoms and cramping may decrease
• May be used by breastfeeding women immediately postpartum (regardless of breastfeeding status) because lactation is not affected
• Possible protection against benign breast disease, endometrial and ovarian cancer and decreased risk of pelvic inflammatory disease (PID)

Disadvantages

• Irregular menses
• May be associated with a higher risk of persistent ovarian follicles
• To be effective, it must be taken at approximately the same time each day
• Concomitant use of certain drugs, eg anticonvulsants, antiretroviral drugs, Rifampicin, medicated charcoal, may lower its effectiveness

Absolute Contraindication

• Current breast cancer

Relative Contraindications

• Gestational trophoblastic neoplasia
• History of breast cancer and no evidence of disease for 5 years
• Severe decompensated cirrhosis
• Acute viral hepatitis
• Liver tumor (adenoma or hepatoma)
• Use of medications that may interfere with POP metabolism (eg anticonvulsants, Rifampicin, Rifabutin) 
• SLE diagnosis with positive antiphospholipid antibodies  
• Acute blood clot in lungs or deep veins of legs

Progestin-only Contraceptive Implants

• Long-acting reversible contraceptives (LARC), these implants contain Etonogestrel or Levonorgestrel
• An implant containing Etonogestrel is effective for 3 years, while Levonorgestrel implants provide contraception for 3-5 years
• Other available implant includes the subcutaneously-administered depot Medroxyprogesterone acetate (DMPA) which appears to be therapeutically similar to injectable DMPA

Indications

• Progestogen implants may be considered in any woman seeking a highly effective, reversible and coitally-independent method of contraception
• They do not require daily attention and are suitable for poorly-compliant women
• Women who are breastfeeding and may be considered in women in whom estrogen is contraindicated

Actions

• Suppresses ovulation, thickens cervical mucus and alters the endometrium

Effects

• Efficacy can be nearly 100%, thus a highly effective, reversible method of contraception
• Efficacy of Levonorgestrel may be reduced near the end of the duration of use stated on the product’s label in patients who are overweight and obese and thus may need implant replacement sooner

Non-Contraceptive Benefits

• Decreased menstrual blood loss per cycle, thus less risk for anemia
• Decreased dysmenorrhea and risk of ectopic pregnancy
• Decreased pain with endometriosis
• Lactation is not affected
• Helps reduce the risk of endometrial cancer

Disadvantages

• Frequent irregular menstrual bleeding and hormonal side effects
• Insertion and removal of the rods require a minor surgical procedure with local anesthesia

Absolute Contraindications

• Same as POPs

Relative Contraindications

• Same as POPs
• Unexplained vaginal bleeding

Progestin-only Injectable Contraceptives

Indications

• Injectable progestins are considered for any woman seeking a highly effective, reversible and coitally-independent method of contraception
• DMPA and Norethisterone enanthate injectables do not require daily attention and are suitable for poorly-compliant women
  • DMPA can be given intramuscularly or subcutaneously
• May be considered in women in whom estrogen is contraindicated
  • Eg women who smoke; women who experience migraine headaches; women who are breastfeeding (started 6 weeks after childbirth; immediately if not breastfeeding); with endometriosis, sickle cell disease; and those taking anticonvulsants
• Parenteral progestins have little or no effect on breast milk production or infant development and therefore, are effective for postpartum contraception

Actions

• Injectable progestins work primarily by inhibiting secretion of gonadotropins and therefore, suppress ovulation
• They also increase viscosity of cervical mucus that blocks sperm entry and induce endometrial atrophy

Effects

• DMPA is effective for 13 weeks while Norethisterone enanthate is effective for 8 weeks
• Injectable progestin use is associated with failure rates in the first year of use of 0.2% in perfect users and 4% in typical users
• Altered bleeding patterns usually occur in 80% of women
• Associated with small loss of bone mineral density (BMD) but reversible after discontinuation

DMPA Non-Contraceptive Benefits

• Amenorrhea and subsequent decrease in dysmenorrhea and risk for iron-deficiency anemia
  • Norethisterone enanthate also helps protect women against iron-deficiency anemia
• Reduced risk of endometrial cancer, ovarian cysts, ovarian cancer, PID, sickle cell crises, and ectopic pregnancy
• Decrease in symptoms associated with endometriosis, PMS and chronic pelvic pain
• Excellent method for women taking anticonvulsant drugs
• Lactation is not affected
• Sickle cell crises are reduced in patients with sickle cell anemia

Disadvantages

• Irregular menstruation during 1st several months
• Hypoestrogenism may occur, which can cause dyspareunia, hot flashes and decreased libido
• May be associated with weight gain, acne and complexion changes
• Must return to the clinic every 11-13 weeks for injection
• Impossible to immediately discontinue

Absolute Contraindications

• Severe coagulation disorders
• History of sex steroid-induced liver adenoma
• Current breast cancer diagnosis

Relative Contraindications

• Liver disease (severe decompensated cirrhosis) or tumors (adenoma or hepatoma)  
• CV disease risk factors
• BP ≥160/100 mmHg 
• Vascular disease, history of ischemic heart disease, stroke 
• Acute deep vein thrombosis (DVT)/pulmonary embolism (PE)
• Past history of breast cancer with no evidence of recurrence for 5 years
• SLE diagnosis with positive antiphospholipid antibodies 
• Unexplained vaginal bleeding 
• DM with retinopathy, nephropathy, neuropathy or DM >20 years in duration

Progestin-only Contraceptive Intrauterine System

• Also a LARC, this releases Levonorgestrel directly into the uterine cavity

Indications

• Women who smoke, especially suited for women who have excessively heavy and painful menstruation; decrease in blood loss protects against iron-deficiency anemia

Actions

• Prevents fertilization, thickens cervical mucus, and impairs sperm passage

Effects

• Effectivity is >99% with perfect use
• Intrauterine system itself may contribute slightly to the contraceptive effect

Non-Contraceptive Benefits

• Reduces risk of endometrial and cervical cancer and risk of ectopic pregnancy
• May aid in the treatment of endometrial hyperplasia, endometriosis and menstrual disturbances during perimenopause 

Disadvantages

•  Include the need to be inserted by a trained healthcare provider and the risk of ectopic pregnancy with failure of treatment or uterine perforation

Contraindications

• Not to be used in women 48 hours-4 weeks postpartum, women with unexplained vaginal bleeding, benign gestational trophoblastic disease, cervical, endometrial, ovarian or breast cancer, fibroids, current PID, purulent cervicitis, distorted uterine cavity, chlamydial or gonorrheal infection, puerperal sepsis, advanced HIV disease, acute blood clot in lungs or deep veins of legs, severe liver cirrhosis or tumor, SLE with positive antiphospholipid antibodies and not on immunosuppressive therapy
  • Use of Levonorgestrel-releasing intrauterine system by patients on Tamoxifen is not associated with breast cancer recurrence

Progesterone-releasing Vaginal Ring

• A flexible silicone vaginal ring that does not contain estrogen  
• It does not protect against sexually transmitted infections 

Indications

• Vaginal ring may be considered for any woman seeking a highly effective, reversible and coitally-independent method of contraception that does not demand daily attention
• Breastfeeding women >4 weeks postpartum can use the progesterone-releasing vaginal ring without restrictions
  • To maintain efficacy, active breastfeeding should be done, eg at least 4x/day  

Action

• Prevents ovulation  

Effect

• Effectivity is 98-99%  

Disadvantages

• Health risks may be similar with that of POPs 

• Also known as postcoital contraception or the morning after pill
• Offered to women who have had an unprotected or inadequately protected intercourse and who do not desire pregnancy
• Intended for occasional use, mainly to back up usual methods of birth control
• Most women experience no side effects but if they do, these do not last long
• Not an abortifacient since it does not disrupt an implanted pregnancy
• Evidence shows that emergency contraceptive pills (ECPs) do not harm the fetus or cause birth defects if pregnancy occurs    
• ECPs can be used more than once, even within the same cycle 
• Though anti-emetics are not routinely given prior to taking ECPs, these may be given to women 0.5-1 hour prior to intake if she had experienced nausea with previous ECP use or with the 1st dose of a 2-dose regimen

Indications

• Failure to use contraceptive method or failure to use additional contraceptive precautions when starting hormonal methods of contraception
• Barrier failure (eg condom breaks or leaks, diaphragm or cervical cap is dislodged)
• Unprotected intercourse or barrier failure during or within 28 days after use of liver enzyme-inducing drugs
• 1 missed pill in the 1st week of COC use or ≥3 missed pills in the 2nd or 3rd week of COC use
• Missed or late POP use
• Late administration of progestin-only injectable
• Partial or complete removal of IUD without immediate replacement
• Ejaculation on the external genitalia
• After sexual assault (if victim is not using any reliable contraception)

Methods

• Should be used as soon as possible or any time up to 5 days after an unprotected sexual intercourse  
• As return of fertility is immediate after taking ECPs, it would not prevent a pregnancy from unprotected sexual intercourse >24 hours after taking ECPs
• Estimated number of pregnancies in 100 women who had unprotected sexual intercourse during the 2nd or 3rd week of the menstrual cycle: COCs 2, POPs 1, Levonorgestrel 1, Ulipristal acetate <1

Hormonal Regimen

• More effective if given earlier
• Combination oral contraceptives (Yuzpe method)
  
  • Combined Ethinyl estradiol and progestins Levonorgestrel, Norgestrel or Norethisterone given for 2 doses, 12 hours apart
    
    • Number of pills to take may vary from 2-5 pills per dose in some preparations  
• Progestin-only pills (eg Levonorgestrel or Norgestrel)  
  • Due to the very small amounts of hormone in POPs, several pills are given per dose (eg 40 pills for 0.0375 mg Levonorgestrel or 0.075 mg Norgestrel; 50 pills for 0.03 mg Levonorgestrel) but are safe to take
• Levonorgestrel (dedicated ECP formulation) 
  • May be given as 2 doses of 0.75 mg Levonorgestrel taken 12 hours apart, or 1 dose of 1.5 mg Levonorgestrel
  • Considered to be a more effective method and with fewer side effects than the Yuzpe method
  • Has been shown to prevent pregnancy by preventing follicular rupture or causing luteal dysfunction
    
    • Not effective once fertilization has occurred and does not affect embryo-endometrial attachment
• Resumption or initiation of any regular contraceptive method may be done immediately (ie the day after the last ECP dose) after emergency contraception with hormonal methods; use of a back-up method for the 1st 7 days is needed  

Antiprogestins

• Mifepristone
  
  • Available in some countries as an effective post-coital contraceptive
  • Aside from binding to progesterone receptors and blocking progesterone effects, may also disrupt luteal phase events and endometrial development
• Ulipristal acetate
  • Shown to inhibit or delay ovulation and suppress growth of lead follicles if taken immediately before ovulation
    • Ineffective in delaying follicular rupture if administered at the time or after luteinizing hormone (LH) peak
  • Has been found to be as effective as Levonorgestrel when taken within 72 hours of unprotected sexual intercourse
  • Either combined hormonal or progestogen-only contraceptives may be resumed or initiated on the 6th day after emergency contraception with Ulipristal acetate; use of a back-up method for the 1st 7 days is needed 

Copper-bearing Intrauterine Device (IUD)

• Should be offered to all eligible women who present within 120 hours after the 1st episode of unprotected sexual intercourse or within 5 days of the earliest date of ovulation
  • Back-up contraception is not needed
• Documented to have low failure rate and shown to be more effective than hormonal emergency contraception, with efficacy of >99%
• Gives long-term protection from pregnancy of up to 12 years; no delay in return of fertility after its removal  
• Decreases the risk of ectopic pregnancy and may help protect against cervical and endometrial cancer  
• Can be given to breastfeeding women within 48 hours after childbirth, otherwise must wait until 4 weeks  
• Should not be given to women 48 hours-4 weeks postpartum, women with unexplained vaginal bleeding, ovarian or cervical cancer, benign gestational trophoblastic disease, current PID, purulent cervicitis, distorted uterine cavity, chlamydial or gonorrheal infection, advanced HIV disease, or SLE with severe thrombocytopenia, or those at high risk for STIs at the time of IUD insertion  
• Routine antibiotic prophylaxis prior to insertion is not indicated  
• Women should undergo a pelvic examination and STI risk assessment before IUD insertion; it is not necessary to remove the IUD during treatment for a positive test result  
• Women should be advised of the risk of PID in the 1st 20 days following insertion if she has gonorrhea or chlamydia