oral contraceptive and beyond

ORAL CONTRACEPTIVE AND BEYOND…….

Dr.bharti singh D.G.O Bharti women’s clinic

• 100 Million worldwide ( WHO1998)

• NFHS II 1999, India– 34% female sterilisation

– OC use 2.19%

– 30% girls have first child before age 19 yearsPearl index - 0.25 per HWYears

Failure rate - 0.3% to 8% ( Perfect versus Typical Use)

What are oral contraceptive pills?

COMPONENTS

• ESTROGEN: ETHINYL ESTRADIOL MESTRANOL-3 methyl ester derivative (mestranol causes increased risk of

tromboembolism;TINDALL)

50 ug standard dose30-35ug low dose20ug ultra low doseStudy-15ug EE /60 ug GESTODENE-24/4.good efficacy and cycle

control(BARBOSA ,CONTRACEPTION 2006)

A comparison of various progestinsPROGESTINS ESTRO

GENICANTIESTROGENIC

ANDROGENIC

ANTIANDROGENIC

ANTIMINERELOCORTICOID

PROGESTERONE - - - + +

OLDER PROGESTINS•MPA - - + - -•NORETHISTERONE - + + - -

•LNG - + + - -

NEWER PROGESTINS•DESOGESTREL

- - - - -

CYPROTERONE ACETATE

- - - + +

•DROSPIRENONE - - - + +

NEWER PROGESTIN

• dienogest a norethindrone-like structure that acts as an antiandrogen

• three 19-norprogesterone derivatives - nestorone nomegestrol acetate trimegestone (sitruk and ware 2006)

Speroff and decherny

MECHANISM OF ACTION

SPIRONOLACTONEProperty Clinical benefit

Progestogenic Antigonadotrophic- inhibits ovulationInhibits endometrial proliferation- ↓ menstrual bleedingCervical mucus thickening

ANTIMINERELOCORTICOID

Promotes salt & water excretion: ↓ wt gain, bloating, BP, mood changes, breast tenderness

ANTIANDROGENIC Effective against acne & hirsutism↑HDL & ↓ LDL Cholesterol

No androgenic action No adverse effect on lipid or glucose toleranceNo wt gain/ acne/ oily skin

No antiestrogenic action

Does not ↓ SHBG, does not ↑ free androgen levels

MONOPHASIC PILLS Type Estrogen PROGESTERONE

Mala N EE 30 ug Norgestrel 300 ug

Mala D EE 30 ug Levonorgestrel 150 ug

Ovral L EE 30 ug Levonorgestrel 150 ug

Ovral G EE 50 ug Levonorgestrel 250 ug

Novelon EE 30 ug Desogestrel 150 ug

Femilon EE 20 ug Desogestrel 150 ug

Loette EE 20 ug Levonorgestrel 100 ug

Yasmin EE 30 ug Drospirenone 3 mg

GINNETE 35,KRIMSON 35, DIANE35

EE 35ug Cyperoterone acetate 2mg

TIRPHASIC PILLSTRIQILAR• .05mg LNG/30 ug EE -5DAYS• .075mg LNG/40 ug EE-NEXT5 DAYS• .125mg LNG/30ug EE-LAST 10 DAYS• Triphasic preparations have been shown to

reduce acne, decrease the incidence of ectopic pregnancy, reduce menstrual blood loss, and lower the frequency of irregular bleeding and menorrhagia.

Extended regimen COC• Also reffered as menstrual suppression• Shorter hormone free interval , similar efficacy.• Decreased escape ovulation , decreased ovarian activity.• Decreased mid cycle break through bleeding.

• Decreased pelvic pain ,breast tenderness ,bloating , swelling.• Useful in perimenopausal women with vasomotor symptoms

• Eg-seasonale,sesonique,(30ug EE/150ug LNG)for 84 daysLybrel(20ug EE/90ug LNG)

• Comparision study shows similar efficacy and side effects with decreased break through bleeding and intermenstrual spotting (ALEXANDER T,2006)

benefits of extended use regimen

• Reduction in risk of ovarian and endometrial cancer

• Relief of dysmenorrhea

• Prevention and treatment of menorrhagia

• Prevention and treatment of anemia in women with bleeding diatheses

• Prevention and treatment of excessive bleeding related to uterine leiomyoma or adenomyosis — Somewomen with heavy menstrual bleeding associated with leiomyomas respond to contraception

• Treatment of pain related to endometriosis

• Prevention of menstrual migraine

• Management of symptoms related to premenstrual syndrome

POTENTIAL BENEFITS OF COC ACOG practical bulletin no 10

• Menstrual cycle regularity• Treatment of acne• Treatment of dysmenorrhea• Treatment of hirsutism• Treatment of menorrhagia• Treatment of pelvic pain from endometriosis• Treatment of premenstrual syndrome

Continued……• Treatment of bleeding from leiomyoma

• Prevention of menstrual migraines

• Improved bone mineral density in older women

• Decreased risk of endometrial, ovarian, and colorectal cancers

• Induction of amenorrhea for lifestyle considerations

DYSMENORRHEA

• Most common menstrual disorder in 50-90% women.

• Due to prostaglandins PGF2ALPHA and PGE2 causing increase myometrial contractility(primary dysmenorrhea).

• 80% decrease in symptoms in primary dysmenorrhea . (ACOG2005)

• Decreases severity in secondary dysmenorrhea of endometriosis (haukesson et al)

• can be used as FIRST LINE TREATMENT(1-A)

• 4 cross-sectional surveys-improvement in pain irrespective of progestational component,estrogen dose,monophasic or multiphasic pill.(lippinccott andwilkins 2007)

• Extended cycle regimens are better.(1-A).(ACOG 2005)

• Not FDA approved.

MENORRHAGIA

• 10% fertile women suffer from menorrhagia.

• Prescribe if no structural or histological abnormality is present or fibroid>3 cm not distorting the cavity (NICE 07)

• Can be used as first line or second line drug specially in women who want to preserve fetility .(ACOG 10)

• 50% decrease in symptoms with both high dose (nilson and solvel 93) and low dose COC.(larsson et al,fraser and mc carron)

• Extended cycle regimen more effective (ACOG 10)

• Can be used in perimenopausal age group after proper evaluation but comes after LNG-IUD(86% after 3 months),TRANEXEMIC ACID in efficacy(A)

PRE MENSTRUAL SYNDROME

PRE MENSTRUAL DYSPHORIC DISORDER

• Premenstrual symptoms,PMS,PMDD-same spectrum with varying severity.

PMS is defined as ‘the cyclic recurrence in the luteal phase of the menstrual cycle of a combination of distressing physical, psychological and/or behavioural changes of sufficient severity to result in deterioration of interpersonal relationships and/or interference with normal activities’ (Reid and Yen, 1981).

• Considered to be the result of complex interaction between ovarian steroids and central neurotransmitters.(Neng/Jmed 1998) .

• 24/4 regimen of 30ug EE/3mg drospirenone is effective in decreasing some physical effects like bloating,breast tenderness,headache and some psychological manifestations by its minerelocorticoid activity and ovarian suppresion.

ACOG 2010

POLYCYSTIC OVARIAN DISEASE

• Usually is the first line treatment

• Normalize androgen levels in 18-21 days

• Non androgenic OCP’s preferred

• Suitable for contraception

• Favorable effect on CHO and lipid metabolism

• Corrects menstrual cycle disturbances

• incidence of anaemia

• Frequency of dysmenorrhoea & pelvic inflammatory disease will be lowered

• in risk of endometrial and ovarian cancer

ROLE IN ACNE TREATMENT

• FDA approval to three preparation• EE WITH• norgestimate(orthotricyclen)• norethindrone(estrostep)• drospirenone (yasmin)• Acts by decreasing the androgens level by GnRH

suppresion and increased SHBG.• Used along with retenoids.• 5 clinical trials-decreases lesion no. in mod to severe

acne.

ROLE IN HIRSUITISM

• OCP are first-line treatment for hirsutism, particularly in those women desiring contraception.

• OCP with DROSPIRENONE(acts as androgen blocker,decreased androgen production and increase SHBG) CYPROTERONE ACETATE(anti androgenic) are used.

• Long term use recommended(A)

ENDOMETRIOSIS• “symptom relief with COC is as good 6 months after treatment

is ended” chochrane review

• ”contraceptive steroidal preparations must therefore be considered drugs of choice and are currently the only safe and economic alternative to surgery”

(The Royal College of Obstetricians and Gynaecologists, 2000).

• “COC reduces menstrual flow,cause decidualisation,decrease cell proliferation and increase apoptosis”

MERESMAN GF 2002

Upto 70% relief in symptoms of endometriosis Vercellini et al., 2003c

CONCLUSION• OCP can be used as first line drugs along

with GnRH agonist and danazole.• gives good symptom relief and helps to cure

the disease to some extent.(more in mild to moderate cases)

• Extended therapy is recommended..

OVARIAN CYST• Ever use of the combined pill was associated with a

decreased risk of nonfollicular benign tumours, including serous and mucinous adenoma, teratoma and endometrioma (OR 0.79, 95% CI 0.6–1.05) (Westhoff et al., 2000).

• The reduction in risk was associated with duration of use.

• combined oral contraceptives should not be used to treat existing functional ovarian cysts.(ACOG 10)

• Can be given to prevent future cyst formation.

OTHER BENEFITS..• BONE MINERAL DENSITY• Beneficial effect in women above 40 yrs using COC for

more than 5 yrs (vessey m ’98)

• younger women who use combined oral contraceptives have a lower BMD compared with nonusers.(ACOG 10)

• LEIOMYOMAS• Case-control studies have reported no effect or reduced

risk of leiomyomas in women who use combined oral contraceptives.

• Can be used to control menstrual pain and flow.

• BENIGN BREAST DISEASE• Includes mainly fibrocystic diesease and

fibroadenoma.• High-dose oral contraceptives may reduce the

risk of BBD (Burkman et al., 2004)• Degree of risk reduction depends on duration

of use (7 yrs reduce by 40%)(ROHAN TE ‘99)

• Protects against ectopic pregnancy.• Prevent menstrual migraine- used as

continuous prophylactic therapy• Prevents progression of reumatoid arthritis

but not a protective factor (spector and hochberg’90)

PID• Barriers are better for STD/HIV protection

• 50% reduction in PID with OC users versus non-users of any method

• Mechanism– Effect on cervical mucus

– Preventing unwanted pregnancies and deliveries

– Reducing unsafe abortions

• Ovarian Cancer – 1.5 to 2 times less in pill users– CASH Study : effect within 6 months, increased to 5 times by

10 years use– Mechanism– chronic suppression of ovulation– chronic gonadotropin suppression– COC with high progestin have greater protective affect

(schildkraut et al)– Protective effect againsy BRCA MUTATION) also (ACOG 10)– Ex-use effect last for 15 years

• Endometrial Cancer– 50% less risk– Effect even with 1 year use– Ex-use effect lasts 15 years

- CASH study N. Engl. J. Med 1987- COLORECTAL CANCER- 18% risk reduction ,more in recent users

(ACOG 10)

Special groups

Used in women with disabilities for hygienic improvement.

In perimenopausal women to control AUB.Nowadays used for decreasing the frequency

of menstruation to increase quality of life.

Take home message……ACOG RECOMMENDATIONS 2010

• The following recommendations are based on good and consistent scientific evidence (Level A):

• Combined oral contraceptives (OCs) should not be used to treat existing functional ovarian cysts.

• Use of combined hormonal contraception has been shown to decrease the risk of endometrial and ovarian cancer.

• Combined OCs have been shown to regulate and reduce menstrual bleeding, treat dysmenorrhea, reduce premenstrual dysphoric disorder symptoms, and ameliorate acne.

• Continuous combined hormonal contraception, depot medroxyprogesterone acetate (DMPA), and the levonorgestrel intrauterine system may be considered for long-term menstrual suppression.

• The following recommendations are based on limited or inconsistent scientific evidence (Level B):

• Based on the limited data available, it appears overall that combined OCs do not increase the risk of development of uterine leiomyomas.

• Hormonal contraception should be considered for the treatment of menorrhagia in women who may desire further fertility.

Definitions:• Grades of Evidence

• I: Evidence obtained from at least one properly designed randomized controlled trial.

• II-1: Evidence obtained from well-designed controlled trials without randomization.

• II-2: Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

• II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.

• III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

• Levels of Recommendations

• Level A —Recommendations are based on good and consistent scientific evidence.• Level B —Recommendations are based on limited or inconsistent scientific

evidence.• Level C —Recommendations are based primarily on consensus and expert opinion.

THANK YOU..