Combined hormonal contraception

(FSRH CHC 2020 amended + EBT)

Types

• COCP
• CTP (combined transdermal patch)
• CVR ( combined vaginal ring)

Hormonal content

• Oestrogen:
  • Contain 35, 30 or 20mcg ethinyl oestradiol (A synthetic oestradiol. Most commonly used)
  •  Pills  containing 50mcg EE are rarely used
  • Other oestrogensà 17β-estradiol structurally identical to that which  occurs naturally in humans

• Mestranol synthetic estrogen (metabolised to EE) is also available (50 μg mestranol roughly equates to 35 μg EE).

• Progestogens

• Progestogens are synthetic steroids designed to have some of the properties of progesterone
• progestogen component of CHC allows convenient dosing intervals, potent suppression of ovulation, and prevents over-proliferation of the endometrium in response to estrogen
• Newer progestogens- fewer androgenic and glucocorticoid effects; some are

anti-androgenic and have potentially favourable anti-mineralocorticoid effects

Progestogen: 

• 2nd generation

1/Norethisterone 1mg ?? generation

2/Levonorgestrel 150mcg  

• 3rd generation

1-Desogestrel 150mcg

2-Gestodene 150mcg

3-Norgestimate 250mcg 

Spironolactone derivative – Drospirenone 3mg (Spironalactone analogue)

Anti-androgen – Dianette, Diane 35

35micg ehinyl oestradiol + 2mg cyproterone acetate

Drospirenone

• Analogue of spironolactone
• Both spiranolactone  and drospirenone are derivatives of progesterone
• Agonist at PR and antagonist at mineralocorticoid receptor
• Have progesterone and antimineralocorticoid activity
• Antagonist at androgen receptor. Anti-androgen
• Anti-androgen effect – more potent than spironolactone ,less potent than cyproterne acetate
• Yasmin , Dronis , Delcia (  EE 30 mic g + dros 3 mg )

Cyproterone acetate

• A progestogen
• With potent anti-androgenic properties
• Has progestogenic activity but no mineralocorticoid activity
• Dianette , Diane 35 (35 mig g EE + 2mg cypro)

Femilon 20 mic g EE+ desogestrel 0.15 mg

Mithuri EE -30mic + LNG 0.15mg

Route

• Combined transdermal patch (CTP) that releases an average of 33.9 μg EE and 203 μg norelgestromin per 24 hours.
• Combined vaginal ring (CVR) that releases EE and etonogestrel at daily rates of 15 μg and 120 μg, respectively.11

Monophasic verses multiphasic COC

• monophasic  biphasic, triphasic and quadriphasic
• Monophasic – all pills in the packet contain the same dose of estrogen and progestogen.
• Multiphasic – dose of either or both steroid hormones varies during the pill cycle

• no particular advantage associated with multiphasic preparations, the
• recommends that monophasic COC should be used first-line

Mechanism of action of CHC

• primary mechanism of action –prevention of ovulation
• acts on the HPO  axis to suppress LH and FSH and thus inhibit ovulation
• Changes to cervical mucus, endometrium and tubal motility that result from progestogen exposure may also contribute to the contraceptive effect

CHC regimens

• Traditional (standard) – 21/7 CHC cycles
• no health benefit from a monthly withdrawal bleed, and the 7-day HFI has the following drawbacks
• Withdrawal bleeding may be heavy, painful
• HFI with headache and mood change
• Ovarian suppression is reduced .Mainly in low dose oestrogen
• Tailored (non-standard
• extended regimens – reduce the frequency of HFI
  • continuous regimens – abolish the HFI
  • Shortened HFI

• extended or continuous CHC regimens and shortened HFI could theoretically reduce risk of escape ovulation compared with standard CHC regimens, but that there is no conclusive evidence of greater contraceptive benefit

• Safety – similar in both regimens according to available data . Cvs, cancer, metabolic

• Bleeding
  • Total number of days of bleeding was lower with continuous or extended regimens than with cyclical use of CHC. Although there was an increase in breakthrough bleeding during the first months of use of continuous or extended regimens, its frequency and intensity subsequently decreased over time.

• Symptoms such as headache, pelvic pain, bloating and breast tenderness are more frequent during the HFI than during the time that CHC hormones are being taken

Starting of CHC

• Assessment before starting CHC
  • Assessment of medical eligibility
  • accurate blood pressure recording should be documented
  • Document BMI before starting
  • Pelvic examination is not required prior to initiation
  • Breast examination, cervical screening, testing for thrombophilia, hyperlipidaemia or diabetes mellitus and liver function tests are not routinely required

Effectiveness of CHC

 Factors afffecting effectiveness of CHC

1. dependent on correct and consistent use

• no association between weight/BMI and effectiveness of COC  

• Limited evidence suggests a possible reduction in patch effectiveness in women ≥90 kg.
• bariatric surgery- effectiveness of COC may be reduced

drug interactions

1. enzyme-inducing drugs – (PCBRAS)
   • Contraceptive effectiveness of CHC could be reduced during use of the enzyme-inducer and for 28 days after stopping.
   • Hepatic enzyme-inducing drugs increase the metabolism of estrogens and progestogens
   • should be offered a method that is unaffected by enzyme-inducers (intrauterine methods or the progestogen-only injectable)
   • If wishes to use COC concomitantly with an enzyme-inducing drug (with the exception of rifampicin or rifabutin which are potent enzyme-inducers) use of a minimum 50 μg (30 μg + 20 μg) EE monophasic combined pill
   • A continuous or tricycling regimen plus a shortened pill-free interval of 4 days should be used

• Lamotrigine
  • Serum levels of lamotrigine can be reduced by CHC
  • so chance of seizure increases
  • Lamotrigine is not thought to be an enzyme-inducing drug, but contraceptive effectiveness of CHC could be reduced by concurrent use of lamotrigine

• Antibiotics (non enzyme-inducing)
  • Additional contraceptive precautions are not required when antibiotics that do not

                  Induce enzymes are used in conjunction with CHCs

• Progestogen receptor modulators
  • wait 5 days after taking UPA-EC before starting CHC –coz can reduce effectiveness of UPA –EC

• Severe diarrhoea or vomiting
  • Reduce effectiveness

MISSED PILL

Non-contraceptive health benefits associated with CHC use

1. Heavy menstrual bleeding treatment
2. Improves Menstrual pain
3. Treatment for acne

• PMS and PMDD

• EE/DRSP COC should be considered a first-line pharmaceutical intervention for management of PMS (GTG)
• A continuous regimen / extended regimen effective than cyclical
• COC other than EE/DRSP – not enough evidence , but may improve symptoms

• Vasomotor symptoms

• COC can help alleviate vasomotor symptoms in perimenopausal women.

• Bone health
• Adolescents

Study- Increase in BMD was significantly greater among non-users than for those

using 21/7 COC, but not for users of the extended regimen 84/7 COC

• Perimenopausal women

use of CHC by women aged over 50 years is not generally recommended

• Endometriosis
• CHC has an important role in the management of endometriosis
• significantly higher rate of remission from endometriosis symptoms and a lower rate of recurrence in women taking COC after surgery compared with surgery alone.
• continuous rather than a cyclical COC regimen is advantageous in the management of endometriosis
• continuous COC use was associated with a significant reduction in dysmenorrhoea and a longer period before dysmenorrhea recurred compared with cyclical use
• reduction in endometriosis-associated pelvic pain, an improvement in sexual activity and quality of life in women on a continuous regimen compared to a 21/7 regimen
• did not identify significant differences in dyspareunia, non-menstrual pelvic pain, or endometriosis recurrence rates between continuous and cyclical users.

• PCOS
• CHC (including the CTP and CVR) for first-line treatment of menstrual irregularity, acne and hirsutism in women with PCOS
• DRSP was effective in treating the symptoms of PCOS

• Effect of CHC use on cancer risk and mortality

• Endometrial cancer
• OC – reduced risk of endometrial cancer that correlates with duration of use and persists for many years ( ? 30 yrs) after cessation
• no significant differences were observed when comparing OC doses and formulations.

• Ovarian cancer
• reduction in risk of ovarian cancer in ever-users of OC compared to never-users
• protective effect is duration-dependent, with women who have used OC for at least 10 years having a 50% reduction in incidence of ovarian cancer
• protective effect observed in women both with and without a genetic predisposition to ovarian cancer
• meta analysis -protection increases with increasing duration of OC use and persists for at least 30 years after cessation

• BRCA gene mutation carriers
  • reduced risk of ovarian cancer with use of COC

• Colorectal cancer
• ever-OC-users have a reduced risk of colorectal cancer compared to never-OC-users

• Mortality
• lower risk of all-cause mortality

Health risks associated with CHC use

1. Venous thromboembolism (VTE)
2. CHC is associated with increased risk of VTE
3. dependent on progestogen type and estrogen dose
4. but the absolute risk of VTE for an individual CHC user remains very small
5. use of low-dose COC (<50 μg EE) containing cyproterone acetate, desogestrel, gestodene or DRSP was associated with a significant 1.5- to 2-fold risk of VTE compared to use of COC containing LNG,  norgestimate

• higher EE dose being associated with greater VTE risk
• Risk of VTE is highest in the months immediately after initiation of CHC or when restarting after a break of at least 1 month
• Frequent stopping and starting of CHC is therefore discouraged.

• Effect of route of administration on VTE risk

• ? high risk of VTE with CTP – no enough evidence
• ? equal or increased risk with CVR than COC- lacking evidence
• Known thrombophilia is an absolute contraindication to CHC use (UKMEC 4).

• Arterial thromboembolic disease
• increased risk of ischaemic stroke and myocardial infarction (MI) compared to non-use of CHC
• risk appears to increase with increasing dose of estrogen in COC
• Risk of MI and ischaemic stroke did not vary clearly according to progestogen type.
• absolute risk of ATE remains extremely small for CHC
• caution or avided in women with multiple risk factors for cardiovascular disease including smoking, hypertension, high BMI, dyslipidaemias and diabetes, and for women with migraine with aura or migraine without aura that is of new onset during use of CHC

• Breast cancer
• Small increased risk of breast cancer which reduces with time after stopping CHC.
• with a family history of breast cancer have an increased background risk of breast cancer compared to women with no such family history
• carriers of known gene mutations associated with breast cancer (e.g. BRCA mutations) the risks of using CHC generally outweigh the advantages

• Cervical cancer
• Current use of CHC for more than 5 years is associated with a small increased risk of cervical cancer; risk reduces over time after stopping CHC and is no longer increased by about 10 years after stopping.
• CVR, CTP no known difference in effects

Side effects associated with CHC use

• many CHC side effects arise during the HFI rather than during active pill use
• shortened HFI or extended/continuous regimens may be helpful

1. headache
2. Commonly reported in HFI
3. ? association between CHC and headache

• Unscheduled bleeding with CHC (breakthrough bleeding)
• a relatively common side effect of CHC
• incidence of unscheduled bleeding decreases with time
• women experiencing unscheduled bleeding continue their method for at least 3 months before seeking advice
• using 20 μg of EE(femilon) experienced higher rates of unscheduled bleeding than women using >20 μg. pills containing second-generation progestogens could offer better cycle control than those containing norethisterone

• Mood
• women may experience negative mood changes when taking CHC
• not clear, consistent evidence that CHC use causes depression
• mood change is common and often related to external events
• a different formulation containing an alternative progestogen could be tried empirically.
• If the negative mood change is premenstrual, continuous use of CHC may be of benefit

• Weight gain
• no clear evidence that use of CHC causes weight gain

• libido
• Libido could be lower among women using COC containing <20 μg EE than in users of COC with ≥20 μg EE.
• No enough evidence

• Return to fertility
• No long-term reduction in fertility
• majority of women ovulate within about a month of COC cessation whether they have used cyclical or extended COC regimens

**** OCP induced hypertension – bradykinin breakdown increases, reduced vasodilatory effect ????

CHC use during travel

• Advice regarding reduce mobility during travel

Surgery/periods of immobilization

• Stop CHC and to switch to an alternative contraceptive method at least 4 weeks prior to planned major surgery or expected period of limited mobility.

In perimenopause

• CHC can be used by medically eligible women for contraception until age 50 years
• CHC can be considered for use by medically eligible women until age 50 as an alternative to HRT for relief of menopausal symptoms and prevention of loss of bone mineral density as well as for contraception

Pearl Index

the number of contraceptive failures per 100 women-years of exposure,

PI= Number of pregnancies * 12                   * 100

        Number of women * Number of months

Unmet need of contraception

Ability to reproduce, Not wanting children/Want to delay pregnancy but not using contraception

Contraception

Deliberate use of artificial methods or other techniques to prevent pregnancy as a consequence of sexual intercourse

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