hormonal%20contraception
HORMONAL CONTRACEPTION
Contraceptive methods are used to prevent pregnancy and sexually transmitted infections (STIs).
Contraception allows women/couples to explore plan on childbearing and family planning.
Hormonal contraception is a method with high rate of effectiveness & ease of administration. It is the widely used method of reversible contraception.
It does not protect against STIs/HIV.

Pharmacotherapy

Combination Oral Contraceptives (COCs)

  • COCs consist of tablets containing both an Estrogen and a Progestin; most widely used formulations
  • Ethinyl estradiol and Mestranol (which is a pro-drug of Ethinyl estradiol) are the estrogens used in combination with any of a number of different progestins
  • 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
    • Some studies have shown that Desogestrel (Progestin derivative)-containing combined OCs are linked with a small increased risk of VTE

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

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 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

Action

  • 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 and 8% in typical users

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 CA
  • 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
  • Smoker ≥35 years old (≥15 cigarettes/day)
    • Increased risk of CV events
  • Obesity (BMI ≥40 kg/m2)
  • Cardiovascular disease
    • History of CVA, ischemic heart disease, multiple risk factors for arterial disease
  • Hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg)
    • May have an increased risk of stroke or MI
  • Current or past history of VTE
    • Increased risk of VTE associated with COC has little impact on healthy women but may greatly increase the risk in women with history of VTE
  • 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
  • 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 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
  • SLE diagnosis with positive antiphospholipid antibodies

Relative Contraindications

  • Breastfeeding between 6 weeks-6 months postpartum
  • <21 days postpartum not breastfeeding without 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 recurrence for 5 years and no known gene mutations associated with breast cancer
  • Currently symptomatic gallbladder disease
  • Mildly compensated cirrhosis
  • History of COC-related cholestasis
  • Users of medications that may interfere with COC metabolism
  • Known hyperlipidemias

Combination Injectable Contraception

  • IM injection of contraceptive consisting of 5 mg Estradiol cypionate and 25 mg Medroxyprogesterone acetate given every months
  • Administered with no more than 33 days between injection

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

  • Prevents contraception primarily by inhibition of ovulation

Effects

  • Return to fertility is rapid and may be as soon as 6 weeks after the last injection

Absolute and Relative Contraindications

  • Similar to COCs

Combination Transdermal Contraceptive Patch

Indications

  • 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

Action

  • Similar to COCs

Effects

  • If properly used, patch can be over 99% effective
    • 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
  • 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 but these have yet to be proven in clinical studies

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 such as detachment, skin irritation and pigment changes on the skin

Absolute and Relative Contraindications

  • Similar to COCs

Combination Vaginal Contraceptive Ring

  • A flexible, nearly transparent ring 54 mm in outer diameter and 4 mm in cross-sectional diameter
  • It releases Estrogen and Progestin at a constant rate/day

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

Action

  • 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 rate is 0.3% in perfect users and 8% in typical users

Non-contraceptive Benefits

  • Non-contraceptive benefits seen in COCs are assumed to be the same with vaginal ring use but these have yet to be proven in randomized controlled trials
  • Better withdrawal bleeding and spotting pattern than COC
  • 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 or 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, 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 >35 years 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

  • POPs are >99% effective when used correctly and consistently
  • The failure rates are approximately 0.3% in compliant patients and 8% 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 because lactation is not affected
  • Possible protection against benign breast disease, endometrial and ovarian cancer and decreased risk of 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 Contraindications

  • Current breast cancer

Relative Contraindications

  • Gestational trophoblastic neoplasia
  • History of breast cancer and no evidence of disease for 5 years
  • Breastfeeding women <6 weeks postpartum
  • Severe decompensated cirrhosis
  • Acute viral hepatitis
  • Liver tumor (adenoma or hepatoma)
  • Use of medications that may interfere with POP metabolism

Progestin-only Contraceptive Implants

  • Contraceptive implants containing Etonogestrel or Levonorgestrel
  • An implant containing Etonogestrel is effective for 3 years, while Levonorgestrel implant provides contraception for 5 years
  • Other available implants include the subcutaneously-administered depot Medroxyprogesterone acetate (DMPA), which appears to be therapeutically similar to injectable DMPA, and the 2-rod Levonorgestrel implant approved for 4-year use ie Sino-implant (II)

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
  • May be considered in women in whom estrogen is contraindicated

Action

  • Prevents ovulation, thickens cervical mucus and suppresses the endometrium

Effects

  • Efficacy can be nearly 100%, thus a highly effective, reversible method of contraception
  • Efficacy is not reduced in patients who are overweight and obese

Noncontraceptive 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
  • May be considered in women in whom estrogen is contraindicated
    • Eg women >35 years who smoke; women who experience migraine headaches; women who are 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

Action

  • 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

  • Each dose is effective for 13 weeks
  • Injectable Progestin use is associated with failure rate of <0.3% in perfect users and 3% in typical users
  • Altered bleeding patterns usually occur in 80% of women
  • Associated with small loss of BMD but reversible after discontinuation

DMPA Non-contraceptive Benefits

  • Amenorrhea and subsequent decrease in dysmenorrhea and risk for 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 significant weight gain, acne and complexion changes
  • Must return to the clinic every 11-13 weeks for injection
  • Impossible to immediately discontinue

Absolute Contraindications

  • Pregnancy
  • Unexplained vaginal bleeding
  • Severe coagulation disorders
  • History of sex steroid-induced liver adenoma
  • Breast cancer diagnosis

Relative Contraindications

  • Liver disease or tumors
  • Severe CV disease
  • Acute DVT/PE
  • Past history of breast cancer with no evidence of recurrence for 5 years
  • Severe depression

Progestin-only Contraceptive Intrauterine System

  • Releases Levonorgestrel directly into the uterine cavity
    • Prevents ovulation, thickens cervical mucus, and impairs sperm passage
  • Effectivity is >99% with perfect use
  • Especially suited for women who have excessively heavy and painful menstruation; decrease in blood loss protects against iron-deficiency anemia
  • Reduces risk of endometrial cancer
  • Not to be used in women with unexplained vaginal bleeding, gestational trophoblastic disease, cervical, endometrial or breast cancer, fibroids, current pelvic inflammatory disease, purulent cervicitis, chlamydial or gonorrheal infection, puerperal sepsis
    • Use of Levonorgestrel-releasing intrauterine system by patients on Tamoxifen is not associated with breast cancer recurrence
  • 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
  • Intrauterine system itself may contribute slightly to the contraceptive effect
  • Return of fertility is rapid and complete after removal
  • It is inserted in the uterus during the 1st 7 days of menstrual cycle (can be inserted at any time if not pregnant) and is effective x 5 years
  •  May be inserted within 48 hours after delivery, >6 weeks after postpartum and immediately post abortion except for septic abortion
    • A higher continuation rate and risk of expulsion are associated with immediate insertion postpartum or post-cesarean section
  • Routine antibiotic prophylaxis prior to insertion is not indicated
  • Women should be advised of the risk of pelvic inflammatory disease in the 1st 20 days following insertion
  • Women at increased risk of STIs should be tested before IUD insertion, though it is not necessary to delay insertion pending test results

Progesterone-releasing Vaginal Ring

  • 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
  • It does not protect against sexually transmitted infections

Emergency Contraception

  • Offered to women who have had an unprotected or inadequately protected intercourse and who do not desire pregnancy
  • Also known as postcoital contraception or the morning after pill
  • Not an abortifacient since it does not disrupt an implanted pregnancy
  • Intended for occasional use, mainly to backup usual methods of birth control
  • It is not recommended to routinely use anti-emetics prior to taking emergency contraceptive pills

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 combined oral contraceptive (COC) use or ≥3 missed pills in the 2nd or 3rd week of COC use
  • Missed or late progestin-only pill (POP) use
  • Late administration of progestin-only injectable
  • Partial or complete removal of intrauterine devices (IUDs) without immediate replacement
  • Ejaculation on the external genitalia
  • Sexual assault, if victim does not use any reliable contraception

Methods

  • Should be used as soon as possible after an unprotected sexual intercourse

Hormonal Regimen

  • More effective if given earlier
  • Combination oral contraceptives (Yuzpe method)
    • Combined 100 mcg Ethinyl estradiol and 0.5 mg Levonorgestrel, given for 2 doses, 12 hours apart
      • Dosing may vary from 2-5 pills in some preparations
    • Has been shown to suppress or delay ovulation and prevents 77% of pregnancies when taken ≤24 hours after intercourse, 36% if within 25-48 hours, and 31% if within 49-72 hours
  • Levonorgestrel
    • 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
    • Has been shown to prevent 95% of pregnancies when taken ≤24 hours after intercourse, 85% if with in 25-48 hours, and 58% if within 49-72 hours
      • Use beyond 72 hours of unprotected intercourse or contraceptive failure is outside the product license
    • Resumption or initiation of any regular contraceptive method may be done immediately after emergency contraception with Levonorgestrel or combination oral contraceptives  

Antiprogestins

  • Mifepristone
    • Available in some countries as an effective post-coital contraceptive
  • Ulipristal
    • 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  

Copper-bearing intrauretine device (IUD)

  • Documented to have low failure rate and shown to be more effective than hormonal emergency contraception, with efficacy of 98.7 to >99%
  • Should be offered to all eligible women who presents 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
  • Women should be advised of the risk of pelvic inflammatory disease in the 1st 20 days following insertion
  • Women at increased risk of sexually transmitted infections (STIs) should be tested before IUD insertion, though it is not necessary to delay insertion pending test results
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Endometriosis is a common gynaecological condition affecting about 6–10% of women of reproductive age and can be a debilitating disease. It is the second most common reason for surgery in premenopausal patients. It is defined as the presence of endometrial-like tissue outside the uterine cavity, leading to a chronic inflammatory reaction. The exact aetiology is unknown, but the retrograde menstruation model is the most widely accepted theory explaining the development of pelvic endometriosis. According to this model, menstrual blood containing endometrial fragments passes through the fallopian tubes into the pelvic cavity, resulting in the formation of peritoneal endometrial deposits. There are three distinctive pathological types of pelvic endometriosis: superficial peritoneal implants, ovarian endometriomas, and deep infiltrating nodular lesions. The extent of the disease is very variable and often does not correlate with the severity of symptoms. Although it can sometimes be asymptomatic (in about 20% of cases), endometriosis is frequently associated with severe pain and infertility. Several management options exist for endometriosis and the choice depends on several factors such as age, fertility, severity of the symptoms, and extent of the disease. This review presents three different cases of endometriosis with different complexities and presentations. The diagnosis and various medical and surgical treatment options available to the clinician will be discussed.