The Promise of Long acting Progestogens

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The Promise of Long acting Progestogens

• By Dr Adarsh Bhargava.
• PHOD, Dept Of Gyn Obstet., State Zenana
  Hospital, Jaipur.

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The Promise of Long acting Progestogens

• Available delivery systems
• CONTRACEPTIVE IMPLANTS
• PROGESTERONE ONLY INJECTABLE CONTRACEPTIVES
• HORMONE RELEASING INTRAUTERINE CONTRACEPTIVE
  DEVICES

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Fact file of long acting progesterone
Contraceptives

• Serum levels of progesterone are detectable
  within hours of insertion
• Reversible with complete return of fertility
• Normal Menstrual cycle returns within 3 to 6
  months of stopping their use.
• Continuous contraceptive protection with use
• Does not contain estrogen
• Constant release of steroid hormone as compared
  to daily administration.
• Require little effort on the part of the user
  therefore theoretical effectiveness is very close
  to the actual or typical (use) effectiveness.

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Fact file of long acting progesterone
Contraceptives

• Inconspicuous
• Does not protect against sexually transmitted
  infections
• As effective as sterilization and non hormonal
  IUDs, more effective than oral and barrier
  contraception.
• A semi invasive procedure
• Requires clinical skill for execution and visit
  to clinician is essential
• Women over 70 kg. or BMI gt 30 can use Long acting
  Progesterone as effective method of
  Contraception.
• May be used in women who have migraine with or
  without aura.
• Appropriate for lactating women

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Progestogen only subdermal implants (POSDIs)
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Past Present of Implants

• Norplant was the first contraceptive implant
  introduced in 1983 consisting of six silastic
  capsules each containing 36 mg. of LNG (not
  frequently used now).
• Jadelle or Norplant II is a newer variant having
  two silastic covered rods of LNG (not frequently
  used now).
• Implanon is the most widely used implant today -
  introduced in 2001.

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IMPLANON

• Single-rod implant (4 cm in length and 2 mm in
  diameter) made of ethylene vinyl acetate and
  contains 68 mg of etonogestrel
• Duration of use 3 years
• Pearl index 0.01 per 100 women yrs

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Presentation of the Packing of Implanon
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Efficacy of Contraceptive Implant with Typical
Use Within the First Year
Percent of Women Experiencing an Unintended
Pregnancy
Combined Oral Contraceptive
Patch
Ring
Implant
Female Sterilization
Injectable Contraceptive
IUD
Pearl index 0.01 per 100 women yrs of use.
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Duration of use and efficacy of Implanon
Duration Mean Peak Serum Concentration of Etonogestrel
Within 8 hours after insertion 266 pg/mL
At 12 months 196-261 pg/mL
At 36 months 156-177 pg/mL
Within 1 week after removal Below sensitivity of assay
Serum concentrations increased within 8 hours to
levels associated with ovulation inhibition.
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Contraceptive Implants - Mechanisms of Action

• Suppresses ovulation
• Occurs within 1 day of insertion
• Ovulation in lt5 of users after 30 months of use
• Increases viscosity of the cervical mucous
• Induces Endometrial atrophy

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Adverse effects of Contraceptive Implants

• Irregular bleeding patterns 36
• (Most important reason for discontinuation)
• Other adverse events
• Acne 14.5
• Emotional lability 14.2
• Headache 12.7
• Weight gain 12.1
• Dysmenorrhea 9.7
• Depression 7.3
• Implant site symptoms
• Mild pain of short duration lt5

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Timing of insertion ofContraceptive Implants

• If no hormonal contraceptive has been used in
  past month
• Insert within 5 days of initiation of menses
• If switching from combination contraceptives,
  insert within 7 days of last active tablet, or
  during the ring-free or patch-free period
• If switching from a progestin-only method
• Any day if using the progestin-only pill
• Same day as intrauterine device or implant
  removal
• On due date for next contraceptive injection
• If the woman is postpartum
• Insert 21 to 28 days after delivery

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Contraceptive Implant Quick Start

• IF using Quick Start method to insert the
  implant
• It may be inserted any time during the menstrual
  cycle
• Determine risk for pregnancy
• Perform pregnancy test, if indicated
• Provide emergency contraception, if indicated
• Recommend nonhormonal contraception for 7 days

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Contraceptive ImplantClient Counseling Tips

• Effectiveness of device
• Mechanism of action
• Side effects, including bleeding patterns
• Risks and complications
• Return to fertility is prompt
• Additional protection required for sexually
  transmitted infections, if necessary
• At insertion and removal of the implant local
  anesthesia will be used

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Myths realities of Contraceptive Implants -

• Not recommended as contraceptive method for women
  taking liver enzyme inducing drugs.
• Serum levels are not affected by antibiotic and
  GI upsets.
• Can be used in women with hypertension, diabetes,
  anemia and endometriosis.
• There is no evidence that implant use increases
  the risk of STI or HIV acquisition.

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Myths realities of Contraceptive Implants -
Contd..

• 94 of women ovulate within 1 month of rod
  removal.
• Insertion and removal are not difficult with
  average timing of insertion 1.1 minute and time
  of removal 2.6 minutes however occasional
  difficulty in removal can be encountered.
• No changes in bone mineral density with use of
  contraceptive implants reported.
• Improvement in ACNE and Dysmenorrhoea

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Progestogen only injectable contraceptives (POICs)
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Types of Progesterone only Injectable
Contraceptives

• Depo-Provera - 150 mg of DMPA via deep
  intramuscular injection in the gluteal or deltoid
  muscle
• Duration of protection 3 months (13 weeks)
• Depo-subQ Provera 104 - 104 mg of DMPA via
  subcutaneous injection into the anterior thigh or
  abdomen (NA in India)
• Duration of protection 3 months (13 weeks)
• Norethisterone enanthate - 200 mg of NET EN via
  deep intra muscular injection in the gluteal
  muscle
• Duration of protection 2 months
• LNG butanoate injectable In research

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(No Transcript)
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Mechanisms of Action of POICs

• Inhibits ovulation
• Suppresses levels of follicle-stimulating hormone
  and luteinizing hormone
• Eliminates surges in luteinizing hormone
• Thickens cervical mucus
• Prevents sperm penetration
• Reduces sperm transport in the fallopian tubes
• Atrophies the endometrium

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Injectable Contraceptives Failure Rate Among
Typical Users Within the First Year
8
8
8
Percentage of Women Experiencing an Unintended
Pregnancy
3
0.5
0.1
0.05
Combined Oral Contraceptive
Patch
Ring
Implant
Female Sterilization
Injectable Contraceptive
IUD
Pearl index 0.3 per 100 women yrs of use.
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Injectable Depot-Medroxyprogesterone Acetate
Disadvantages

• Bleeding irregularity amenorrhea progressively
  more common
• Weight gain (gt2 kg) is common and cumulative
• Depression may occur, but overall rates not
  increased
• Bone density decreases - Start oral calcium
  vit D when on DMPA
• Cannot discontinue method immediately
• Side effects may continue until DMPA clears from
  the womans body approximately 6 to 8 months
  after the last injection
• Return to fertility may take 6 to 12 months after
  discontinuation
• Return visits required every 11 to 13 weeks
• Changes in lipid profile
• Does not protect against human immunodeficiency
  virus and other sexually transmitted infections

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Injectable Depot-medroxyprogesterone Acetate
Noncontraceptive Benefits

• Likely to cause amenorrhea in from 25 to 50 of
  women at one year, which many women consider to
  be an advantage
• Decreased menstrual cramps, pain, mood changes,
  headaches, breast tenderness, and nausea
• Reduced risk of ovarian cancer
• Reduced risk of pelvic inflammatory disease
• Decreased pain associated with ovulation and
  endometriosis
• Can be used in women taking enzyme inducing drugs
  without decrease in dosage interval

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Return to Fertility After Cessation of Injectable
Depot-Medroxyprogesterone Acetate (DMPA)
Cumulative Contraception Rate ()
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Timing of Progesterone only Injectable
Contraceptive Injection

• Initial injection
• On day 1 to 5 of menstrual cycle
• Within first 5 days of the postpartum period if
  not breastfeeding
• After the 6th postpartum week if breastfeeding
• Immediately or within the first 7 days after an
  abortion
• Reinjection
• At week 11 to 13
• If injection is missed or late (14 weeks),
  back-up contraception should be used and absence
  of pregnancy should be confirmed

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Who can use DMPA
WHO Category Conditions
Category 1 Heavy smokers, breastfeeding after six weeks postpartum, thyroid disorders, severe dysmenorrhoea, uterine fibroids, STIs/PID
Category 2 lt18 years, adequately controlled hypertension, uncomplicated diabetes, gall-bladder disease, use of the antibiotic rifampicin or anticonvulsants
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Who should not use DMPA
WHO Category Conditions
Category 3 Breastfeeding before 6 weeks postpartum, severe hypertension (gt160/gt100), vascular disease, current DVT/PE, current or history of ischemic heart disease or stroke, complicated diabetes, active viral hepatitis, severe cirrhosis, liver tumors
Category 4 Current breast cancer
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Levonorgestrel Intrauterine System(LNG-IUS)
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Progesterone Intrauterine System i.e. LNG 20 IUD
(LNG 20, Mirena, Levonova)

• It is a T shape device having a collar attached
  to the vertical arm.
• Contains 52 mg LNG dispersed in polydimethyl
  siloxane and released initially _at_ 20 µg/day in
  vivo.
• Duration of use 5 years
• Pearl index 0.1 per 100 women yrs of use.

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Mechanisms of Action

• Levonorgestrel-Releasing Intrauterine System
  (LNG-IUS, Mirena)
• Inhibits fertilization
• Thickens cervical mucous
• Inhibits sperm function
• Thins and suppresses the endometrium

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Efficacy of LNG- IUS

• It is about as effective as sterilization with
  pearl index of 0.1 to 0.3 per 100 women years of
  use.
• Return of Fertility
• Return of fertility is prompt

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Timing of Insertion of LNG-IUS

• Any time during menses
• Any other time during a womans cycle if
• - She used appropriate contraception
• - She was not sexually active, or
• - Her pregnancy test was negative
• Any time after a pregnancy, a spontaneous
  abortion, a miscarriage, or an induced abortion
  if a woman has not engaged in unprotected
  intercourse
• Precaution
• Emergency drugs including anti-epileptic
  medication should be available at the time of IUS
  insertion in a woman with epilepsy because there
  may be an increased risk of a seizure at the time
  of cervical dilation.
• Always exclude pregnancy

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Tips for Health Care Professionals

• IUD use is not contraindicated in nulliparous
  women of any age.
• Women of all ages may use IUS.
• Can be safely used in women who are
  breastfeeding.
• No evidence that effectiveness of IUS is reduced
  when taking any other medication.
• Not contraindicated in women with diabetes
  mellitus.
• Women with history of venous thromboembolism may
  use IUS

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Non contraceptive benefits of LNG-IUS

• Effective in the treatment of menorrhagia
• Prevention treatment of endometrial hyperplasia
  
• Decreases menstrual loss and pelvic infection
  rates
• Local progestin effect can be of use in women on
  tamoxifen, dysmenorrhoea and post menopausal
  women receiving estrogen therapy
• Regulates menstrual cycle and reduces cramps

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Side effects of LNG-IUS

• Effect on menstrual pattern
• Irregular bleeding and spotting in first six
  months.
• Oligo or amenorrhoea by the end of fist year of
  IUS use.
• Acne
• Uterine perforation at the time of insertion (lt1
  in 1000)
• Risk of developing PID at the time of insertion
  (lt1 in 100 in women who are at low risk of STIs).
• IUS may be expelled (lt1 in 20 in 5 year of use)
• Risk of ectopic pregnancy is less than when using
  no contraception however if a woman becomes
  pregnant with IUS in situ the risk of ectopic
  pregnancy is 1 in 20.

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WHO risk category indications for LNG-IUS
Medical Conditions LNG-IUS WHO Risk Category
Hypertension (controlled) 1
Multiple cardiovascular risk factors 2
History of DVT or pulmonary embolism 2
Stroke 2
Severe valvular heart disease (complicated) 2
HIV infection 2
AIDS (clinically well on antiretroviral therapy) 2
Medical Condition LNG-IUS WHO Risk Category
Known thrombogenic mutations 2
Migraines with aura 2
Epilepsy 1
Diabetes 2
Obesity 1
Thyroid disorders 1
Viral hepatitis (active infection) 3
Viral Hepatitis (carrier) 1
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Thanks to all contributors.

• Dr Adarsh Bhargava.
• Dr Ashwini Bhalerao.
• Dr Alka Kriplani.
• Dr. Kalpana Apte.
• Dr Mala Arora.
• Dr.Meenakshi Bharath.
• Dr. Mandakini Parihar.
• Dr.Nozer Sheriar.
• Dr.Parikshit Tank.
• Dr. Roza Olyai.
• Dr.Sasikala Kola.
• Dr.Sujata Mishra.