Royal College of Obstetricians and Gynaecologists

Setting standards to improve womens health

FACUL ! OF S"#UAL $ R"%RO&UC '(" )"AL )CAR"

Faculty of Sexual & Reproductive Healthcare Clinical Guidance

Management of Unscheduled Bleeding in omen Using Hormonal Contraception

Clinical !ffectiveness Unit May "##$

%SS& '())*'#+,

Published by the Faculty of Sexual and Reproductive Healthcare Registered in England No. 28 !2"# and Registered $harity No. " "%%&% First published in 2 % 'Faculty (ebsite version updated in Septe)ber 2 % %*

$opyright + Faculty of Sexual and Reproductive Healthcare 2

Per)ission granted to reproduce for personal and educational use only. $o))ercial copying, hiring and lending are prohibited.

FACUL ! OF S"#UAL $ R"%RO&UC '(" )"AL )CAR"

Faculty of Sexual and Reproductive Healthcare Clinical !ffectiveness Unit in colla-oration .ith the Royal College of /-stetricians and Gynaecologists

Royal College of Obstetricians and Gynaecologists

Setting standards to improve womens health

FSRH Guidance 0May "##$1 Management of Unscheduled Bleeding in omen Using Hormonal Contraception
'-ate of planned revision 2 "!*
Purpose and scope .his /uidance brings together evidence and expert opinion on the )anage)ent of unscheduled bleeding in (o)en using hor)onal contraception 0i.e. co)bined oral contraceptive pill '$1$*, transder)al patch, progestogen2 only pill 'P1P*, in3ectable, i)plant or intrauterine syste) '45S*6. .he ter) unscheduled bleeding in this /uidance refers to brea7through bleeding, spotting, prolonged or fre8uent bleeding '9ox "*." .he )anage)ent of (o)en (ho present (ith unscheduled bleeding (hile using hor)onal contraception is challenging. For )any (o)en unscheduled bleeding (ill be due to the contraceptive )ethod itself, and the pattern and duration of bleeding and the li7elihood of this settling (ill vary (ith the )ethod used '.able "*.2:"# ;o)en )ay consider that the contraceptive benefits of a )ethod )ay out(eigh the inconvenience of unscheduled bleeding. <fter reassurance that there is no serious underlying cause they )ay be happy to continue use. .he )anage)ent of (o)en (ith unscheduled bleeding in the initial )onths 'i.e. #:& )onths* after starting a ne( )ethod of hor)onal contraception )ay differ fro) that of (o)en (ho continue to have unscheduled bleeding in the longer ter) or (ho present (ith a change in bleeding pattern. < clinical history '9ox 2* should highlight possible underlying causes 'an exa)ple being Chlamydia trachomatis* and provide a guide to the )ost appropriate exa)ination, investigation and treat)ent
Box '2 Clinically important -leeding patterns in .omen aged ')344 years' SCH!5U6!5 B6!!5%&G U&SCH!5U6!5 B6!!5%&G Fre7uent -leeding 8rolonged -leeding %rregular -leeding Spotting Brea9through -leeding
a9leeding

options re8uired. Reassuringly in co))unity populations, endo)etrial cancer is very rare in (o)en of reproductive age (ho are using hor)onal contraception or (ho do not have ris7 factors for endo)etrial cancer 'such as obesity, polycystic ovarian syndro)e, ta)oxifen use or unopposed estrogen therapy*. $ervical cancer is also rare in this population, especially in (o)en (ho co)ply (ith National $ervical Screening Progra))es. < )anage)ent plan is outlined and can be tailored to the individual (o)an 'Figure "*. Evidence to support the )anage)ent plan is provided in this /uidance. .his )anage)ent plan is provided as a guide only and can be used to develop a local care path(ay ta7ing account of local expertise or ease of referral>access to specialist services and investigations. Reco))endations are provided (here evidence exists. /ood practice points have been given (here no evidence exists but are based on the clinical 3udg)ent and opinion of the expert )ultidisciplinary group developing this /uidance 'see <ppendix*. .his /uidance is not intended to serve alone as a standard of )edical care, as this should be deter)ined individually based on available clinical infor)ation. .his /uidance has been syste)atically developed using the standard )ethodology outlined in the <ppendix to this docu)ent. 9ac7ground -uring a nor)al )enstrual cycle the endo)etriu) is exposed to circulating sex steroids. 4t is the se8uential exposure of the endo)etriu) to the natural steroids, estradiol and progesterone, that leads to the characteristic histological features."! Estradiol exposure during the follicular phase is responsible for endo)etrial proliferation. Exposure to progesterone in the luteal phase results in secretory differentiation. Progesterone is anti2estrogenic and inhibits endo)etrial gro(th and glandular differentiation. 4t is the (ithdra(al of estrogen and progesterone, in the absence of pregnancy, that triggers the onset of )enstrual bleeding."? Exogenous ad)inistration of sex steroids, in the for) of hor)onal contraception, (ill dra)atically influence endo)etrial histology. .he endo)etrial response to hor)onal contraception (ill reflect circulating sex hor)one concentrations plus the dose and for)ulation of steroid delivery, the route of delivery of the steroid, and the ti)ing and duration of ad)inistration."?,"& .he exact )echanis)s of unscheduled bleeding associated (ith hor)onal contraception have yet to be explained. .he evidence to date i)plicates superficial blood vessel fragility (ithin the endo)etriu) as a

=enstruation or regular (ithdra(al bleeding (ith co)bined hor)onal contraception 're8uiring sanitary protection*"

=ore than five bleeding episodesa 1ne or )ore bleeding episodes lasting "! days or )ore" 9et(een three and five episodes (ith fe(er than three bleeding2free intervals of length "! days or )ore" =ay not re8uire the use of sanitary protectionb 5nscheduled bleeding in (o)en using hor)onal contraceptionb

episodes 'reference periods* are used to describe patterns of bleeding over ti)e. .he first reference period begins on the first day of )ethod use and lasts at least % days. b-efinitions of spotting and brea7through bleeding used in this /uidance.

+ * FSRH 2

+ FSRH 2 *%

C!U GU%5:&C!

C!U GU%5:&C!

;a-le ' Expected bleeding patterns after co))encing hor)onal contraception and in the longer ter)2:"#, 2 Contraceptive method C/MB%&!5 H/RM/&:6 C/&;R:C!8;%/& 'pill, patch or ring* 8R/G!S;/G!&*/&6< C/&;R:C!8;%/& Progestogen2only pill Bleeding patterns in .omen in the first + months 5p to 2 @ of co)bined oral contraception users have irregular bleeding. No significant differences bet(een pill or patch use.2:! Bleeding patterns in .omen in the longer term 9leeding usually settles."% 1varian activity is effectively suppressed.

1ne2third of (o)en have a change in bleeding and " in " have fre8uent bleeding.?

9leeding )ay not settle (ith ti)e and ovarian activity is inco)pletely suppressed. <pproxi)ately " :"?@ are a)enorrhoeicA up to ? @ have a regular bleedA # :! @ have irregular bleeding." 5p to B @ are a)enorrhoeic at " year.&

Progestogen2only in3ectable Progestogen2only i)plant

9leeding disturbances 'spotting, light, heavy or prolonged bleeding* are co))on.B,2 5p to #?@ are a)enorrhoeic at # )onths.& 9leeding disturbances are co))on.%

<fter & )onths use, # @ have infre8uent bleedingA " :2 @ have prolonged bleeding.&,"2 Cong2acting reversible contraceptive 'C<R$* guidance suggestsD 2 @ are a)enorrhoeicA ? @ have infre8uent, fre8uent or prolonged bleeding, (hich )ay not settle (ith ti)e.&

Cevonorgestrel2 releasing intrauterine syste)

4rregular, light or heavy bleeding is co))on 'in the first & )onths*.2

&?@ have a)enorrhoea or reduced bleeding at " year.& < % @ reduction in )enstrual blood loss has been de)onstrated over "2 )onths of use."","#

consistent proble)atic feature. 4n addition, local changes in endo)etrial steroid response, structural integrity, tissue perfusion and local angiogenic factors are li7ely to contribute."& Since there are no established long2ter) interventions available to )anage unscheduled bleeding, a greater understanding of the )echanis)s involved is re8uired. 9leeding pattern expected (ith hor)onal contraceptives Pre2)ethod counselling about expected bleeding patterns )ay reduce concerns and encourage continued use of the )ethod."B,"8 4f bleeding patterns fall outside the expected nor)al patterns associated (ith different contraceptive )ethods at different durations of use '.able "* then exa)ination, investigation or treat)ent )ay be indicated.2:"#,"%:2"

'

Before starting hormonal contraception= .omen should -e advised a-out the expected -leeding patterns= -oth initially and in the longer term> 0Good 8ractice 8oint1

=edical eligibility criteria for contraceptive use in (o)en (ith bleeding .he UK Medical Eligibility Criteria for Contraceptive Use '5E=E$* provides reco))endations for the safe use of contraception. 22 $ategories for use of hor)onal contraception by (o)en (ith vaginal bleeding are su))arised in .able 2. =anage)ent of (o)en (ith unscheduled bleeding <n individual approach should be ta7en (hen considering

;a-le " 5E =edical Eligibility $riteria for contraceptive use in (o)en (ith different patterns of vaginal bleeding22 ?aginal -leeding patterns 4rregular bleeding (ithout heavy bleeding Heavy or prolonged bleeding 'includes regular or irregular* 5nexplained vaginal bleeding 'suspicious of serious pathology* before evaluation Com-ined hormonal contraception " 8rogestogen*only pill 2 8rogestogen*only in@ecta-le 2 8rogestogen*only implant 2 6evonorgestrel* releasing intrauterine system "

"

4nitiation " $ontinuation 2

4nitiation ! $ontinuation 2

5E=E$ "D < condition for (hich there is no restriction for the use of the contraceptive )ethod. 5E=E$ 2D < condition for (hich the advantages of using the method generally outweigh the theoretical or proven risks. 5E=E$ #D < condition (here the theoretical or proven risks usually outweigh the advantages of using the method.a 5E=E$ !D < condition that represents an unacceptable health risk if the contraceptive )ethod is used. 4nitiationD Starting a )ethod of contraception by a (o)an (ith a specific )edical condition. $ontinuationD $ontinuation of a )ethod already being used by a (o)an (ho develops a ne( )edical condition.
a.he

provision of a )ethod to a (o)an (ith a condition given a 5E=E$ $ategory # re8uires expert clinical 3udge)ent and>or referral to a specialist contraceptive provider since use of the )ethod is not usually reco))ended unless other )ethods are not available or not acceptable.

Box "2 8oints to cover in the clinical history from a .oman using hormonal contraception .ho presents .ith unscheduled -leeding $linical history ta7ing should include an assess)ent of the (o)anFsD 1(n concerns $urrent )ethod of contraception and the duration of usea 5se of the current contraceptive )ethodb 5se of )edications 'including over2the2counter preparations* that )ay interact (ith the contraceptive )ethod, or any illness that )ay affect the absorption of orally ad)inistered hor)ones $ervical screening historyc Ris7 of sexual trans)itted infections 'i.e. for those aged G2? years, or at any age (ith a ne( partner, or )ore than one partner in the last year* 9leeding pattern before starting hor)onal contraception since starting and currently <ny other sy)pto)s suggestive of an underlying cause 'e.g. abdo)inal or pelvic pain, postcoital bleeding, dyspareunia, heavy bleeding* .he possibility of pregnancy
aProgestogen2only

< pregnancy test should be perfor)ed if there has been incorrect )ethod use 'such as )issed pills, late in3ection or expelled 45S*, drug interactions or illness, (hich )ay alter absorption of oral )ethods. No evidence (as identified to suggest that unscheduled bleeding in a (o)an (ho has been using her hor)onal )ethod consistently and correctly is associated (ith an increased ris7 of pregnancy. " : clinical history should -e ta9en from .omen using hormonal contraception .ith unscheduled -leeding to identify the possi-ility of an underlying cause> 0Grade C1 Hormonal contraceptive users .ith unscheduled -leeding .ho are at ris9 of S;%s 0i>e> those aged A") years old= or .ho have a ne. sexual partner= or more than one partner in the last year1 should -e tested for C. trachomatis as a minimum> ;esting for N. gonorrhoeae .ill depend on sexual ris9 and local prevalence> 0Good 8ractice 8oint1 omen using hormonal contraception .ho have unscheduled -leeding .ho are not participating in a &ational Cervical Screening 8rogramme should have a cervical screen> 0Good 8ractice 8oint1 : pregnancy test is indicated for .omen using hormonal contraception .ith unscheduled -leeding if the clinical history identifies the possi-ility of incorrect method use= drug interactions or illness= .hich may lead to mala-sorption of oral hormones> 0Good 8ractice 8oint1 hen may examination &/; -e re7uiredB 5nscheduled bleeding in the first # )onths after starting a ne( hor)onal contraceptive )ethod is co))on '.able "*. /enital exa)ination is not re8uired if after ta7ing a clinical history there are no ris7 factors for S.4s, no concurrent sy)pto)s suggestive of underlying causes, and the (o)an is participating in a National $ervical Screening Progra))e 'Figure "*. So)e (o)en )ay be happy to continue (ith the )ethod after this initial assess)ent but follo(2up should be planned as bleeding )ay persist. C %n general= in .omen attending .ith unscheduled -leeding using hormonal contraception= examination may not -e re7uired if after ta9ing a clinical history there are no ris9 factors for S;%s= no concurrent symptoms suggestive of underlying causes= and the .oman is participating in a &ational Cervical Screening 8rogramme> 0Good 8ractice 8oint1 hen is examination re7uiredB Providing there has been consistent and correct use of hor)onal contraception, exa)ination is (arranted to visualise the cervix by speculum exa)ination 'Figure "*D For persistent bleeding beyond the first # )onths use For ne( sy)pto)s or a change in bleeding after at least # )onths use of a )ethod 4f the (o)an has not participated in a National $ervical Screening Progra))e

)ethods are )ore li7ely to present (ith unscheduled bleeding than co)bined hor)onal )ethods, and bleeding (ith progestogen2only pills is less li7ely to settle than bleeding (ith the progestogen2only in3ectable. bFor exa)ple, )issed pills. c< (o)an presenting (ith abnor)al bleeding (ho is participating in a National $ervical Screening Progra))e does not re8uire a cervical screen unless one is due.

the )anage)ent of (o)en using hor)onal contraception (ho present (ith unscheduled bleeding. .he decision to exa)ine, investigate and>or treat (ill depend on a clinical assess)ent '9ox 2*. .he clinician )a7ing an assess)ent of (o)en using hor)onal contraception (ith unscheduled bleeding shouldD .a7e a clinical history Exclude sexually trans)itted infections 'S.4s* $hec7 the cervical screening history $onsider the need for a pregnancy test. < clinical history '9ox 2* should be ta7en to identify or exclude so)e of the possible underlying causes of unscheduled bleeding in (o)en using hor)onal contraception. .he need for exa)ination and investigation (ill be deter)ined fro) the clinical history. <ssess)ent of )ethod co)pliance is an i)portant part of the clinical history 'e.g. pill ta7ing, patch use*. <ll (o)en using hor)onal contraception (ho have unscheduled bleeding should be assessed to identify the ris7 of sexually transmitted infections 'S.4s*. Chlamydia trachomatis is the )ost co))on bacterial S.4 in the 5E and although up to 8 @ of (o)en (ith C. trachomatis are asy)pto)atic abnor)al bleeding )ay be a presenting sy)pto).2#:2? Ris7 factors for S.4s include age G2? years, or a ne( sexual partner, or )ore than one partner in the last year.2#:2? 4f dee)ed at ris7 for an S.4, C. trachomatis should be excluded as a )ini)u). < self2 obtained lo( vaginal s(ab 'S1CHS* can be offered 'if available locally* or a first2void urine 'FH5* if a speculu) exa)ination is not being perfor)ed. .he decision to test for Neisseria gonorrhoeae (ill depend on the (o)anFs individual sexual ris7 and the prevalence of this infection locally and if dual testing is available as a routine. < cervical screening test is not a diagnostic test of cancer. .he cervical screening history should be chec7ed to ensure that (o)en are participating in a National $ervical Screening Progra))e. .his )ay have been chec7ed (hen hor)onal contraception (as initiated but should be revie(ed if a (o)an presents (ith unscheduled bleeding. < cervical screen can be ta7en if due or overdue. No evidence (as identified to support cervical screening if not due.2&:28

For all .omen using hormonal contraception .ith unscheduled -leeding + ;a9e a clinical history to assess2 o ;o)anFs concerns o $orrect use of the )ethod 'e.g. pill ta7ing, patch use*, use of interacting )edication, illness altering absorption of orally ad)inistered hor)ones o 1ther sy)pto)s 'e.g. pain, dyspareunia, abnor)al vaginal discharge, heavy bleeding, postcoital bleeding* + !xclude sexually transmitted infections + Chec9 cervical screening history + Consider the need for a pregnancy test

Manage any issues identified a-ove

6ess than + months since starting the method <ll of the above chec7ed and confir)ed>excluded. .hereafter a genital exa)ination and further investigation 'biopsy scan, hysteroscopy* are not re8uired unless re8uested by the (o)an. Reassure and arrange follo.*up> 4f re8uested, )edical )anage)ent can be considered 'see Figure 2*.
Note& "N# $U% users with pain' discharge or lost threads in addition to bleeding re(uire investigation to e)clude e)pulsion' perforation or infection. a 3 months is an arbitrary cut off and not strongly evidence based. Notable bleeding is common in the first ! months of use with "N# $U% and progestogen only implants.

More than + months use .ith + Persistent bleeding + Ne( sy)pto)s or changed bleeding pattern + Failed )edical treat)ent + Not participating in a cervical screening progra))e + 4f re8uested by the (o)an
a

3 months is an arbitrary cut off and not strongly evidence

based. Notable bleeding is common in the first ! months of use with "N# $U% and progestogen only implants.

<s above <N- in addition pain, dyspareunia, or abnor)al vaginal discharge

Speculum examination to assess cervix 'e.g. polyps, ectopy* Nor)al findings Speculum and -imanual examination

:t follo.*up 9leeding persists or after failed )edical treat)ent 5nscheduled bleeding settled No other sy)pto)s

$linical findings refer>)anage appropriately

Sy)pto)s 'pain, dyspareunia, heavy bleeding*

<ge ,!? years or G!? years but (ith ris7 years factors endo)etrial <ge I!? orfor G!? years but (ith ris7 factors for endo)etrial cancer
cancer

$ontinue (ith the )ethod

Reassure Reassure $onsider $onsider)edical )edical )anage)ent )anage)ent 'see Figure 2*

$onsiderfurther further assess)ent assess)ent 'endo)etrial 'endo)etrial $onsider assess)ent such as (ith ultrasound scan, assess)ent such as (ith ultrasound scan, biopsy, hysteroscopy* depending on age biopsy, hysteroscopy* depending on age and li7elihood of pathology and li7elihood of pathology

CN/245S, levonorgestrel2releasing intrauterine syste).

ure ' Exa)ple of a )anage)ent plan for a (o)an using hor)onal contraception (ith unscheduled
Figure ' Exa)ple of a )anage)ent plan for a (o)an using hor)onal contraception (ith unscheduled bleeding

Medical therapy options for .omen using hormonal contraception .ith unscheduled -leeding *based on e)pert clinical +udgment of the multidisciplinary group developing this #uidance,

Com-ined hormonal contraceptive users

8rogestogen*only pill users

8rogestogen*only implants= in@ecta-le or intrauterine system

4n general, continue (ith (ith the thesa)e sa)e general, continue pill for at least least # # )onths )onths as as bleeding bleeding )ay )ay settle settle in in this thisti)e. ti)e. 5se a $1$ $1$ (ith (ith a a dose dose of of EE EEto to provide provide the the best best cycle cycle control. control. =ay consider consider increasing increasing the theEE EE dose up to a a )axi)u) )axi)u) of of#? #?Jg.

=ay try a different P1P although there is no evidence that changing the progestogen type or increasing the dose i)proves bleeding. No evidence that desogestrel2only pills 8rogestogen*only pill have better bleeding users patterns than traditional P1Ps. =ay try a different P1P No evidence to support although there is no per the use of t(o P1Ps evidence that changing day to i)prove bleeding. the progestogen type or increasing the dose i)proves bleeding. No evidence that desogestrel2only pills have better bleeding patterns than traditional

first2line $1$ $1$ '# '# :#? : Jg < first2line (ith levonorgestrel levonorgestrelor or EE (ith norethisterone* )ay )aybe be norethisterone* considered considered for for up up to to # # )onths )onths continuously continuously or orin in the usual usual cyclical cyclicalregi)en regi)en 'unlicensed*. 'unlicensed*.
No No evidence evidence reducing reducing 8rogestogen*only in3ection in3ection interval interval for for-=P< -=P< implants= in@ecta-le or i)proves ho(ever i)proves bleeding, bleeding, ho(ever intrauterine system the in3ection in3ection can can be be given givenup up to 2 (ee7s (ee7s early. early. < first2line $1$ '# :#? Jg EE (ith levonorgestrel or =efena)ic acid ? )g =efena)ic acid ? ? )g )g =efena)ic acid norethisterone* )ay be t(ice 'or as licensed use up t(ice 'or as licensed use up t(ice 'or as licensed use up considered forfor up ? to # for to three for ? days for three daily* daily* for ? days for to three* daily days )onths continuously or in (o)en (ith (ith bleeding bleeding on (o)en on the usual cyclical regi)en -=P< -=P< to to reduce reduce the the 'unlicensed*. duration duration of of the the bleeding bleeding interval, long2ter) interval, no nothe long2ter) duration of bleeding No evidence reducing benefit. benefit. no long2ter) interval, in3ection interval for -=P< benefit. i)proves bleeding, ho(ever

Com-ined hormonal contraceptive users =ay try try a a different different $1$ $1$ but butno no evidence one evidence one better better than than any anyother other ter)s of in ter)s of cycle cycle control. control. 4n general, continue (ith the sa)e pill for at least # )onths as evidence changing No evidence changing bleeding )aydose settle intype this ti)e. progestogen or progestogen dose or type i)proves cycle i)proves cycle control control but but)ay )ay 5se a $1$ (ith a dose of EE to on an basis. help an individual individual basis. provide the best cycle control. .here are no data on )anaging control o .here =ay consider are noincreasing data on the EE bleeding associated patch. .here are no data (ith on the control of f bleeding dose up to associated a )axi)u) (ith of the #? Jg. patch. $ontinue for at least # )onths as bleeding associated (ith the patch. $ontinue for at least )onths bleeding )ay settle in # this ti)e. as $ontinue for at least # )onths as bleeding settle$1$ in this ti)e. =ay try a)ay different but no

bleeding )ay settle in this ti)e.

$1$, co)bined oral contraceptive pillA -=P<, depot )edroxyprogesterone acetateA EE, ethinylestradiolA P1P, progestogen2 only pill. Figure " =edical therapy options for (o)en using hor)onal contraception (ith unscheduled bleeding

4f re8uested by the (o)an <fter a failed trial of the li)ited )edical )anage)ent

available 'Figure 2* 4f there are other sy)pto)s such as pain, dyspareunia or postcoital bleeding 'N9. .hese sy)pto)s (ould also (arrant -imanual examination.* .he #2)onth cut2off is given here as a guide only as so)e )ethods, in particular the 45S or progestogen2 only i)plant, )ay co))only cause bleeding after the first # )onths of use. Hisualisation of the cervix can identify cervical conditions 'such as polyps or ectopy*, (hich )ay (arrant referral for appropriate )anage)ent. =ost cases of cervical cancer are identified by screening. Ho(ever, visualisation of the cervix )ay identify the very occasional case of cervical cancer that can present (ith abnor)al vaginal bleeding. Referral for gynaecological exa)ination and an urgent referral to colposcopy is re8uired if cancer is suspected on exa)ination.2&,28

/uidance fro) the National 4nstitute for Health and $linical Excellence 'N4$E* on the )anage)ent of (o)en (ith heavy )enstrual bleeding 2% reco))ends a speculu) and bi)anual exa)ination if there are additional sy)pto)s 'such as inter)enstrual or postcoital bleeding, pelvic pain or pressure sy)pto)s suggestive of a structural or histological abnor)ality*. .his advice about exa)inations is appropriate for (o)en (ith unscheduled bleeding using hor)onal contraception. ( 8roviding there has -een consistent and correct use of hormonal contraception= a speculum examination should -e performed for .omen using hormonal contraception .ith unscheduled -leeding if they have2 persistent -leeding or a change in -leeding after at least + months useD failed medical treatmentD if they have not participated in a &ational Cervical Screening 8rogramme> 0Good 8ractice 8oint1

8roviding there has -een consistent and correct use of hormonal contraception in addition to a speculum examination= a -imanual examination should -e performed for .omen using hormonal contraception .ith unscheduled -leeding if they have other symptoms 0such as pain= dyspareunia or heavy -leeding1> 0Good 8ractice 8oint1

%n general= an endometrial -iopsy should -e considered in .omen aged ,4) years 0or in .omen aged A4) years .ith ris9 factors for endometrial cancer 0e>g> o-esity or polycystic ovarian syndrome1 .ho have persistent unscheduled bleeding after the first 3 months of starting a method or .ho present .ith a change in bleeding pattern> 0Good 8ractice 8oint1

hen is further investigation 0endometrial -iopsy= ultrasound scan or hysteroscopy1 re7uiredB <n endometrial -iopsy is indicated if endo)etrial cancer or hyperplasia is suspected. Reassuringly, ho(ever, endo)etrial cancer is rare in (o)en of reproductive age and in addition (o)en using hor)onal contraception have a lo(er ris7 of endo)etrial cancer.# .he co))only used endo)etrial sa)pling devices )ay fail to obtain a sa)ple ade8uate for pathological diagnosis in up to " @ of (o)en.#" .he use of hor)onal contraception 'e.g. progestogen2only in3ectable, (hich induces endo)etrial atrophy* )ay )a7e obtaining an ade8uate endo)etrial sa)ple difficult.#2 .here is no guidance available for clinicians on the role for endo)etrial biopsy in (o)en using hor)onal contraception (ho present (ith unscheduled bleeding. < N4$E /uideline reco))ends that for (o)en (ith heavy )enstrual bleeding an endo)etrial biopsy should be perfor)ed if there is persistent inter)enstrual bleeding, and in (o)en aged ,!? years (ho have treat)ent failure.2% .his advice )ay also be useful for (o)en using hor)onal contraception (ith unscheduled bleeding. .a7ing account of the lac7 of direct evidence and the 7no(ledge that endo)etrial cancer is rare in (o)en of reproductive age, the $linical Effectiveness 5nit '$E5* reco))ends that an endo)etrial biopsy )ay be considered in (o)en aged ,!? years. <n endo)etrial biopsy is also reco))ended in (o)en aged G!? years (ith ris7 factors for endo)etrial cancer 'e.g. obesity, polycystic ovarian syndro)e, ta)oxifen use or unopposed estrogen therapy* if unscheduled bleeding persists after the first # )onths of starting a contraceptive )ethod or (ho present (ith a change in bleeding pattern. .here is no guidance available for clinicians on the role of transvaginal ultrasound scan and hysteroscopy in (o)en using hor)onal contraception (ho present (ith unscheduled bleeding. < specific assess)ent of endo)etrial thic7ness is of li)ited value in pre)enopausal (o)en but )ay identify structural abnor)alities such as uterine polyps or sub)ucosal fibroids.2%,## < N4$E /uideline reco))ends that an assess)ent of the uterine cavity via transvaginal ultrasound scan or hysteroscopy )ay be indicated in (o)en (ith heavy )enstrual bleeding (ho also have signs or sy)pto)s 'such as inter)enstrual or postcoital bleeding, pelvic pain, pelvic )ass* suggestive of a structural abnor)ality.2% .here is a lac7 of direct evidence that structural abnor)alities 'such as uterine polyps or intrauterine fibroids* are the cause of bleeding in (o)en using hor)onal contraception (ith unscheduled bleeding. 4f, ho(ever, these structural abnor)alities are suspected a transvaginal scan and>or hysteroscopy )ay be considered.

'# ;he role of uterine polyps= fi-roids or ovarian cysts as a cause of unscheduled -leeding is limited> &evertheless= for all .omen using hormonal contraception .ith unscheduled -leeding= if such a structural a-normality is suspected a transvaginal ultrasound scan andFor hysteroscopy may -e indicated> 0Good 8ractice 8oint1 .reat)ent options for (o)en (ith unscheduled bleeding using hor)onal contraception <lthough nu)erous research studies have atte)pted to investigate preventative and therapeutic treat)ents for (o)en using hor)onal contraception (ith unscheduled bleeding, none are of sufficient 8uality to guide )anage)ent in clinical practice usefully.#! <s a result of this lac7 of evidence, /ood Practice Points based on the opinion of the expert group have been given in this section unless other(ise stated. .he UK %elected -ractice .ecommendations for Contraceptive Use2 '5ESPR* provide reco))endations on the )anage)ent of )enstrual abnor)alities in (o)en using progestogen2only i)plants, in3ectable or 45S. 9leeding (ith hor)onal contraceptives is co))on in the first fe( )onths of use and )edical therapy ideally should be delayed until after the first # )onths of use. Ho(ever, if re8uested by the (o)an the li)ited therapeutic options can be considered in this ti)e. ;reatment options for .omen using com-ined hormonal contraception 5nscheduled bleeding is less co))on (ith co)bined 'estrogen and progestogen* hor)onal )ethods than (ith progestogen2only )ethods."% <ny unscheduled bleeding (ith the co)bined oral contraceptive pill '$1$* use usually settles (ith ti)e and therefore changing the $1$ to another $1$ in the first # )onths is not generally reco))ended. ;o)en should use a $1$ (ith the lo(est dose of ethinylestradiol 'EE* to provide good cycle control.#?,#& $ycle control )ay be better (ith $1$s containing # :#? -g EE than 2 -g EE.#? -ata do not support increasing the dose of EE in (o)en already using a # -g $1$.#B Nevertheless, increasing the dose of EE to #? -g )ay i)prove bleeding patterns for so)e (o)en. <lthough individual studies suggest bleeding )ay be better (ith $1$s containing certain progestogens#8:! this is not evident in syste)atic revie(s.!" 5sing a $1$ (ith an extended cycle is safe and (ell tolerated and indeed the nu)ber of days of bleeding is reduced.!2:!% Ho(ever, there are currently no good data to support the use of a continuous regi)en over the licensed cyclical regi)es to i)prove bleeding.!8 < $ochrane revie( concluded there (as insufficient evidence to reco))end the use of a biphasic and triphasic $1$ to i)prove bleeding patterns.! 5nscheduled bleeding 'brea7through bleeding and

spotting* (ith the contraceptive patch appeared si)ilar to that for a triphasic $1$ in a rando)ised, co)parative trial.? 5nscheduled bleeding (as )ore co))on in $ycles " and 2 (ith patch use than (ith $1$ use.# '' %t is not generally recommended that a com-ined oral contraceptive pill is changed .ithin the first + months of use as -leeding distur-ances often settle in this time> 0Good 8ractice 8oint1 '" For .omen using a com-ined oral contraceptive pill the lo.est dose of ethinylestradiol 0!!1 to provide good cycle control should -e used> Ho.ever= the dose of !! can -e increased to a maximum of +) -g to provide good cycle control> 0Good 8ractice 8oint1 ;reatment options for .omen using progestogen* only contraception < $ochrane revie( investigated preventive and therapeutic treat)ents of bleeding associated (ith progestogen2only contraception. #! No evidence (as identified to suggest that bleeding patterns (ith one progestogen2only )ethod (ill predict the li7ely bleeding patterns (ith another progestogen2only )ethod. -rogestogen only pills .here is a lac7 of evidence on the effective treat)ent of bleeding in (o)en using P1Ps. Studies have investigated the use of an estrogen?" or an anti2 progestogen ?2 versus placebo for the treat)ent of bleeding associated (ith P1P use (ith little effect. No evidence (as identified that suggests one P1P is associated (ith less bleeding than any other 'including the desogestrel2only pill*. <lthough bleeding )ay settle (ith ti)e, there is no definite ti)e fra)e in (hich (o)en can expect bleeding to stop or i)prove. .here is no evidence that bleeding i)proves (ith t(o P1Ps per day, although this has been used in clinical practice. -rogestogen only in+ectable contraception 1ne trial?# in a $ochrane revie(#! evaluated the effect of estrogen on bleeding in (o)en using depot )edroxyprogesterone acetate '-=P<*. .his rando)ised trial included 2B8 (o)en using -=P< (ith irregular bleeding (ho (ere rando)ised to receive either EE '? -g*, estrogen sulphate '2.? )g* or placebo daily for "! days. <lthough this trial of therapeutic treat)ent (as designed to identify both short2 and long2ter) effects, there (as a high rate of discontinuation '! @ in each group* thus giving a )a3or ris7 of bias. 1nly EE (as effective in stopping bleeding in the "! days of treat)ent 0relative ris7 'RR* .2&, %?@ confidence interval '$4* ."": .& 6. 4n the # )onths follo(ing treat)ent, ho(ever, any ongoing beneficial effects of ? -g EE on bleeding (as )ini)al 'RR . &, %?@ $4 . :". *. 1ne trial investigated the use of a non2steroidal anti2 infla))atory drug 'NS<4-* ')efena)ic acid* for bleeding in (o)en using -=P<.?! ;o)en had to have at least 8 days bleeding or spotting prior to participating in the trial and to be bleeding on the day of recruit)ent. .his s)all, rando)ised, double2blind, placebo2controlled trial found that )efena)ic acid '? )g t(ice daily for ? days* (as effective in reducing a bleeding episode.?#,?! .he usual regi)en for )efena)ic acid is ? )g three ti)es daily but there are no studies investigating this dose and its

effect on bleeding. <round B @ of (o)en had stopped bleeding (ithin B days of starting )efena)ic acid 'co)pared to ! @ (ith placeboA pG . ?*. .here (as no significant difference in the )ean bleed2free interval in the longer ter) '28 days follo(ing treat)ent*. < $ochrane revie(#! included trials using estrogen 'oral diethylstilbestrol, oral 8uinesterol or a "B. estradiol transder)al patch* as a preventative treat)ent for (o)en starting -=P<. .he individual trial results (ere difficult to interpret (ithin the )eta2analysis and discontinuation rates (ere high. < rando)ised controlled trial sho(ed that )ifepristone '? )g as a single dose on -ay "! and every 2 (ee7s for six cycles* reported a significant reduction in brea7through bleeding co)pared to (o)en given placebo.?? .here is no direct evidence on the use of a lo(2dose 'G? -g* $1$ to treat unscheduled bleeding in (o)en using progestogen2only in3ectable contraception. -espite this the 5ESPR supports the use of EE 'given as a $1$* as a short term treatment option in (o)en (ith light or heavy bleeding (ith progestogen2only in3ectable contraception. No reco))endation (as given regarding the use of an NS<4- in the 5ESPR2 and /orld 0ealth 1rgani2ation %elected -ractice .ecommendations for Contraceptive Use.B =ore recent evidence of short2ter) benefit of )efena)ic acid has been published.?! 9ased on li)ited evidence, the $E5 reco))end that as a first line option a $1$ )ay be used by (o)en using progestogen2only in3ectable contraception (ith unscheduled bleeding if there are no contraindications to use of estrogen. .he $1$ can be used for up to # )onths (hile continuing (ith -=P< 'unlicensed use*. .he $1$ can be ta7en in the usual cyclic )anner '(ith a (ithdra(al bleed* or continuously (ithout a pill2free interval. 9ased on )ore recent evidence?! for (o)en (ho have a contraindication to $1$ use then )efena)ic acid '? )g t(ice or three ti)es daily for ? days* )ay be considered to attenuate a bleeding episode but there is no evidence that this approach has an effect on bleeding patterns in the longer ter). < s)all rando)ised controlled trial?& suggested that there is so)e evidence that a $ox2 2 inhibitor 'valdecoxib* is effective in the treat)ent of uterine bleeding (ith -=P<, ho(ever the use of $ox22 inhibitors for this purpose is unlicensed in the 5E. -rogestogen only implants -ata relating to )anage)ent of bleeding proble)s associated (ith the etonogestrel i)plant '4)planonK* are li)ited.& -ata extrapolated fro) studies in (o)en using a levonorgestrel i)plant 'NorplantK* provide so)e evidence of a beneficial effect of )efena)ic acid or EE 'alone or as an oral contraceptive* on bleeding patterns.?B:&" .o date there are no data to indicate (hether or not the sa)e (ill be true for the etonogestrel i)plant '4)planon*. Estrogen generally has been reported to have a beneficial effect in stopping bleeding in (o)en using Norplant and )ay reduce irregular bleeding during treat)ent. Ho(ever, discontinuation due to estrogenic side effects of nausea (as co))on. < co)bination of oral EE '? -g* (ith levonorgestrel '2? -g* ta7en for 2 consecutive days in Norplant users reduced bleeding during treat)ent and up to 8 (ee7s after treat)ent (hen co)pared to placebo. ?% .his co)bined approach significantly reduced continued irregular bleeding during treat)ent co)pared to placebo 'RR . 8, %?@ $4 . #: .2!* and reduced unacceptable bleeding 'as defined by the nu)ber of (o)en having bleed2free intervals of G"" days* after treat)ent 'RR . 2, %?@ $4

. : .2%*. .here is li)ited evidence that levonorgestrel ' . # )g* given alone t(ice daily for 2 days fro) the eighth consecutive day of bleeding reduced the nu)ber of days of bleeding over the follo(ing year of Norplant use.&" Research suggests that doxycycline and )ifepristone )ay also be beneficial but there is li)ited evidence to support their use in routine clinical practice.#?,&2:&! For (o)en (ith light or heavy bleeding (ith a progestogen2only i)plant, the use of estrogen as $1$ or an NS<4- is reco))ended in the 5ESPR. 2 Nevertheless, the dosing regi)e and duration of use are not specified. "evonorgestrel releasing $U% No evidence (as identified on treat)ent options for (o)en (ith unscheduled bleeding (ith the levonorgestrel2releasing 45S. /ood provision of infor)ation about expectations of bleeding patterns li7ely to be experienced is an i)portant part of )anage)ent. '+ Bleeding is common in the initial months of progestogen*only method use and may settle .ithout treatment> %f treatment may encourage .omen to continue .ith the method it may -e considered> 0Good 8ractice 8oint1 '4 ;here is no evidence that changing the type and dose of progestogen*only pills .ill improve -leeding -ut this may help some individuals> 0Good 8ractice 8oint1 ') For .omen .ith unscheduled -leeding using a progestogen*only in@ecta-le= implant or %US .ho .ish to continue .ith the method and are medically eligi-le= a C/C may -e used for up to + months 0this can -e in the usual cyclic manner or continuously .ithout a pill*free interval1> 0Good 8ractice 8oint1 'C For .omen using a progestogen*only in@ecta-le contraceptive .ith unscheduled -leeding= mefenamic acid )## mg t.ice daily 0or as licensed up to three times daily1 for ) days can reduce the length of a -leeding episode -ut has little effect on -leeding in the longer term> 0Grade B1
References " 9elsey E=, Pinol EP. =enstrual bleeding patterns in untreated (o)en. Contraception "%%BA ))D ?B:&?. 2 Lie)an =, /uillebaud M, ;eisberg E, Shangold /<, Fisher <$, $reasy /;. $ontraceptive efficacy and cycle control (ith the 1rtho EvraK>EvraK transder)al syste)D the analysis of pooled data. 3ertil %teril 2 2A ((D S"#:S"8. # Faculty of Fa)ily Planning and Reproductive Healthcare $linical Effectiveness 5nit. Ne( Product Revie( 'Septe)ber 2 #*. Norelgestro)in>ethinyl oestradiol transder)al contraceptive syste) 'Evra*. 4 3am -lann .eprod 0ealth Care 2 !A +#D !#:!?. ! $rosignani P/, .esta /, Hegetti ;, ParaNNini F. 1varian activity during regular oral contraceptive use. Contraception "%%&A )4D 2B":2B#. ? =c$ann =F, Potter CS. Progestin2only oral contraceptionD a co)prehensive revie(. Contraception "%%!A )#D S"?%:S"88. & National 4nstitute for Health and $linical Excellence 'N4$E*. "ong 5cting .eversible Contraception& 6he Effective and 5ppropriate Use of "ong 5cting .eversible Contraception. 2 ?. httpD>>(( (.nice.org.u7>/uidance>$/# 0<ccessed B Manuary 2 %6. B ;orld Health 1rganiNation. %elected -ractice .ecommendations for Contraceptive Use '2nd edn*. 2 ?. httpD>>(((.(ho.int>reproductive2health> publications>sprJ2>index.ht)l 0<ccessed B Manuary 2 %6. 8 <7tun H, =oroy P, $a7)a7 P, Oalcin HR, =olla)ah)utoglu C,

"

"" "2 "#

"! "? "& "B

"8

"% 2

2" 22

2#

2!

2?

2&

2B 28

2%

-anis)an N. -epo2ProveraD use of a long2acting progestin in3ectable contraceptive in .ur7ish (o)en. Contraception 2 ?A ("D 2!:2B. Fun7 S, =iller ==, =ishell -R, <rcher -F, Poindexter <, Sch)idt M, et al. Safety and efficacy of 4)planon, a single2rod i)plantable contraceptive containing etonogestrel. Contraception 2 ?A ('D #"%:#2&. Faculty of Sexual and Reproductive Health $are $linical Effectiveness 5nit. FSRH /uidance 'Nove)ber 2 8* -rogestogen only -ills. 2 8. httpD>>(((.ffprhc.org.u7>ad)in> uploads>$E5/uidanceProgestogen1nlyPill 8.pdf 0<ccessed B Manuary 2 %6. <ndersson E, 1dlind H, Rybo /. Cevonorgestrel2releasing and copper2releasing 'Nova .* 45-s during five years of useD a rando)iNed co)parative trial. Contraception "%%!A 4$D ?&:B2. <ffandi 9. <n integrated analysis of vaginal bleeding patterns in clinical trials of 4)planon. Contraception "%%8A )ED %%S: " BS. 4rvine /<, $a)pbell29ro(n =9, Cu)sden =<, Hei77ilP <, ;al7er MM, $a)eron 4.. Rando)ised co)parative trial of the levonorgestrel intrauterine syste) and norethisterone for treat)ent of idiopathic )enorrhagia. 7r 4 1bstet #ynaecol "%%8A '#)D ?%2:?%8. Noyes R;, Hertig <., Roc7 M. -ating the endo)etrial biopsy. 5m 4 1bstet #ynecol "%B?A '""D 2&2:2&# Mabbour HN, Eelly R;, Fraser H=, $ritchley H1-. Endocrine regulation of )enstruation. Endocr .ev 2 &A "(D "B:!&. S)ith 1P, $ritchley H1. Progestogen only contraception and endo)etrial brea7 through bleeding. 5ngiogenesis 2 ?A ED ""B:"2&. Halpern H, /ri)es -<, CopeN C=, /allo =F. Strategies to i)prove adherence and acceptability of hor)onal )ethods for contraception. Cochrane 8atabase %yst .ev 2 &A 'D $- !#"B. $anto -e $etina .E, $anto P, 1rdoQeN Cuna =. Effect of counseling to i)prove co)pliance in =exican (o)en receiving depot2)edroxyprogesterone acetate. Contraception 2 "A C+D "!#:"!&. Rosenberg =M, Cong S$. 1ral contraceptives and cycle controlD a critical revie( of the literature. 5dv Contracept "%%2A ED #?:!?. Faculty of Fa)ily Planning and Reproductive Health $are $linical Effectiveness 5nit. UK %elected -ractice .ecommendations for Contraceptive Use . 2 2. httpD>>(( (. f fprhc.org.u7>ad)in>uploads>Final@2 5E@2 reco))endations".pdf 0<ccessed B Manuary 2 %6. ;estoff $, Heart(ell S, Ed(ards S, Lie)an =, $ush)an -, Eal)uss -. 1ral contraceptives discontinuationD do side effects )atterR 5m 4 1bstet #ynecol 2 BA (4D "%":"%2. Faculty of Fa)ily Planning and Reproductive Health $are $linical Effectiveness 5nit. UK Medical Eligibility Criteria for Contraceptive Use '5E=E$ 2 ?>2 &*. 2 &. httpD>>(( (. ffprhc.org.u7>ad)in>uploads>5E=E$2 ? &.pdf 0<ccessed B Manuary 2 %6. Faculty of Fa)ily Planning and Reproductive Health $are and 9ritish <ssociation of Sexual Health and H4H. .he )anage)ent of (o)en of reproductive age attending non2 genitourinary )edicine settings (ith a co)plaint of vaginal discharge. 4 3am -lann .eprod 0ealth Care 2 &A +"D ##:!2. Scottish 4ntercollegiate /uidelines Net(or7 'S4/N*. Management of #enital Chlamydia trachomatis $nfection 'S4/N Publication No. !2*. 2 . httpD>>(((.sign.ac.u7>guidelines> fulltext>!2>index.ht)l 0<ccessed B Manuary 2 %6. 9ritish <ssociation for Sexual Health and H4H '9<SHH*. 9::! National #uideline for the Management of #enital 6ract $nfection with Chlamydia 6rachomatis. 2 &. httpD>>(((. bashh.org>docu)ents>&">&".pdf 0<ccessed B Manuary 2 %6. Scottish 4ntercollegiate /uidelines Net(or7 'S4/N*. Management of Cervical Cancer& 5 National Clinical #uideline 'S4/N Publication No. %%*. 2 8. httpD>>(((.sign.ac.u7>pdf> sign%%.pdf 0<ccessed B Manuary 2 %6. Shapley =, Mordon M, $roft PR. < syste)atic revie( of postcoital bleeding and cervical cancer. 7r 4 #en -ract 2 &A )CD !?#:!& . NHS $ervical Screening Progra))e 'NHS$SP*. Colposcopy and -rogramme Management& #uidelines for the N0% Cervical %creening -rogramme 'NHS$SP Publication 2 *. 2 !. httpD>>(((.cancerscreening.nhs.u7>cervical>publications>nhscs p2 .pdf 0<ccessed B Manuary 2 %6. National 4nstitute for Health and $linical Excellence 'N4$E*. 0eavy Menstrual 7leeding 'N4$E $linical /uideline !!*. 2 B. httpD>>(( (.nice.org.u7>nice)edia>pdf>$/!!N4$E/uideline.pdf 0<ccessed B Manuary 2 %6. Scottish 4ntercollegiate /uidelines Net(or7 'S4/N*. $nvestigation of -ost Menopausal 7leeding 'Section 2D Ris7 of Endo)etrial $ancer* 'S4/N Publication No. &"*. 2 2.

#"

#2

##

#!

#?

#&

#B #8 #% ;.

httpD>>(( (.sign.ac.u7>guidelines>fulltext>&">index.ht) l 0<ccessed B Manuary 2 %6. /ordon S, ;estgate M. .he incidence of failed pipelle sa)pling in a general outpatient clinic. 5ust N ; 1bstet #ynaecol "%%%A +$D ""?: ""8. Sereepapong ;, $hotnopparatpattara P, .aneepanichs7ul S, =ar7ha) R, Russell P, Fraser 4S. Endo)etrial progesterone and estrogen receptors and bleeding disturbances in depot )edroxyprogesterone acetate users. 0um .eprod 2 !A '$D ?!B:??2. $ritchley H1-, ;arner P, Cee <M, 9rechin S, /uise M, /raha) 9. Evaluation of abnor)al uterine bleedingD co)parison of three outpatient procedures (ithin cohorts defined by age and )enopausal status. 0ealth 6echnol 5ssess 2 !A E'#!*D iii:iv, ":"#%. <bdel2<lee) H, dF<rcangues $, Hogelsong E, /ul)eNoglu <=. .reat)ent of vaginal bleeding irregularities induced by progestin only contraceptives. Cochrane 8atabase %yst .ev 2 BA 4D $- #!!%. /allo =F, Nanda E, /ri)es -, SchulN EF. .(enty )icrogra)s vs. I2 -g estrogen oral contraceptives for contraceptionD syste)atic revie( of rando)iNed controlled trials. Contraception 2 ?A ('D "&2:"&%. <7erlund =, Rode <, ;estergaard M. $o)parative profiles of reliability, cycle control and side effects of t(o oral contraceptive for)ulations containing "? )icrogra)s desogestrel and either # )icrogra)s or 2 )icrogra)s ethinyl oestradiol. 7r 4 1bstet #ynaecol "%%#A '##D 8#2:888. Edel)an <, EoontN SC, Nichols =, Mensen M.. $ontinuous oral contraceptivesD are bleeding patterns dependent on the hor)ones givenR 1bstet #ynecol 2 &A '#(D &?B:&&?. Rosenberg =M, ;augh =S, Higgins ME. .he effect of desogestrel, gestodene, and other factors on spotting and bleeding. Contraception "%%&A )+D 8?:% . Endri7at M, Hite R, 9anne)erschult R, /erlinger $, Sch)idt =ulticenter, co)parative study of cycle control, efficacy and tolerability of t(o lo(2dose oral contraceptives containing 2 )icrogra) ethinyl oestradiol>" )icrogra) levonorgestrel and 2 )icrogra) ethinyl oestradiol>? )icrogra) norethisterone. Contraception 2 "A C4D #:" . Han Hliet H<<=, /ri)es -<, Hel)erhorst F=, SchulN EF. 9iphasic versus triphasic oral contraceptives for contraception. Cochrane 8atabase %yst .ev 2 &A +D $- #28#. =aitra N, Eulier R, 9loe)en7a)p E;, Hel)erhorst F=, /ul)eNoglu <=. Progestogens in co)bined oral contraceptives for contraception. Cochrane 8atabase %yst .ev 2 !A +D $- !8&". <nderson F-, Hait H. < )ulticenter, rando)iNed study of an extended cycle oral contraceptive. Contraception 2 #A CED 8%:%&. Sula7 PM, $arl M, /opa /opala7rishnan 4, $offee <, Euehl .M. 1utco)es of extended oral contraceptive regi)es (ith a shortened hor)one2free interval to )anage brea7through bleeding. Contraception 2 !A (#D 28":28B. Sula7 PM, Euehl .M, $offee <, Phar) -, ;illis M. Prospective analysis of occurrence and )anage)ent of brea7through bleeding during an extended oral contraceptive regi)en. 5m 4 1bstet #ynecol 2 &A '$)D %#?:%!". <rcher -F, Mensen M., Mohnson MH, 9orisute H, /rubb /S, $onstantine /-. Evaluation of a continuous regi)en of levonorgestrel>ethinyl estradiolD phase # study results. Contraception 2 &A (4D !#%:!!?. =iller C, Notter E. =enstrual reduction (ith extended use of co)bination oral contraceptive pillsD rando)iNed controlled trial. 1bstet #ynecol 2 "A $ED BB":BB8. E(iecien =, Edel)an <, Nichols =-, Mensen M.. 9leeding patterns and patient acceptability of standard or continuous dosing regi)ens of a lo(2dose oral contraceptiveD a

!8 !%

?"

?2

?#

?! ??

?&

?B

?8

!"

?% & &" &2

!2 !#

!!

&#

!?

!& !B

&!

rando)iNed trial. Contraception 2 #A C(D %:"#. =iller C, Hughes MP. $ontinuous co)bination oral contraceptive pills to eli)inate (ithdra(al bleedingD a rando)iNed trial. 1bstet #ynecol 2 #A '#'D &?#:&&". Edel)an <, /allo =F, Nichols =, Mensen M., SchulN EF, /ri)es -<. $ontinuous versus cyclic use of co)bined oral contraceptives for contraceptionD syste)atic $ochrane revie( of rando)iNed controlled trials. 0um .eprod 2 &A "'D ?B#:?B8. <udet =$, =oreau =, Eoltun ;-, ;aldbau) <S, Shangold /, Fisher <$, et al. Evaluation of contraceptive efficacy and cycle control of a transder)al contraceptive patch vs an oral contraceptiveD a rando)iNed controlled trial. 45M5 2 "A "E)D 2#!B:2#??. Mohannisson E, Candgren 9=, -icNfalusy E. Endo)etrial )orphology and peripheral steroid levels in (o)en (ith and (ithout inter)enstrual bleeding during contraception (ith the # )icrogra) norethisterone 'NE.* )inipill. Contraception "%82A 'D "#:# . /e)Nell2-anielsson E, /e)Nell2-anielsson E, Eillic7 SR, $roxatto H9, 9ouchard P, $a)eron S, et al. 4)proving cycle control in progestogen2only contraceptive pill users by inter)ittent treat)ent (ith a ne( anti2progestogen. 0um .eprod 2 2A "D ?88:?%#. Said S. $linical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in (o)en using depot )edroxyprogesterone acetate for contraception. 0um .eprod "%%&A ''D ":"#. .anti(attana7ul P, .aneepanichs7ul S. Effect of )efena)ic acid on controlling irregular uterine bleeding in -=P< users. Contraception 2 !A (#D 2BB:2B%. Main ME, Nicosia <F, Nucatola -C, Cu MM, Euo CM, Felix M$. =ifepristone for the prevention of brea7through bleeding in ne( starters of depo2)edroxyprogesterone acetate. %teriods 2 #A CED """?:"""%. Nathiro3ana7un P, .aneepanichs7ul S, Sappa7it7u)3orn N. Efficacy of a selective $ox22 inhibitor for controlling irregular uterine bleeding in -=P< use. Contraception 2 &A (+D ?8!:?8B. Eae(rudee S, .aneepanichs7ul S, Maisa)rarn 5, Reinprayoon -. .he effect of )efena)ic acid on controlling irregular uterine bleeding secondary to NorplantK use. Contraception "%%%A C#D 2?:# . <lvareN2SancheN F, 9rache H, .hevenin F, $ochon C, Faundes <. Hor)onal treat)ent for bleeding irregularities in Norplant i)plant users. 5m 4 1bstet #ynecol "%%&A '(4D %"%: %22. ;it3a7sono M, Cau .=, <ffandi 9, Rodgers P<. 1estrogen treat)ent for increased bleeding in Norplant usersD preli)inary results. 0um .eprod "%%&A ''D " %:""!. ;u SC. $hanges in liver function and three )etabolites before and after subder)al i)plantation (ith Norplant. %heng2hi <u 7iyun "%%2A '"D B!:B?. -iaN S, $roxatto H, PaveN =, 9elhad3 H, Stern M, Sivin 4. $linical assess)ent of treat)ents for prolonged bleeding in users of Norplant i)plants. Contraception "%% A 4"D %B:" %. $heng C, Lhu H, ;ang <, Ren F, $hen M, /lasier <. 1nce a )onth ad)inistration of )ifepristone i)proves bleeding patterns in Norplant i)plant users. 0um .eprod 2 A ')D "%&%:"&B2. =assai =R, PaveN =, Fuentealba 9, $roxatto H, dF<rcangues $. Effect of inter)ittent treat)ent (ith )ifepristone on bleeding patterns in Norplant i)plant users. Contraception 2 !A (#D !B:?B. ;eisberg E, Hic7ey =, Pal)er -, 1F$onnor H, Sala)onsen C<, Findlay ME, et al. < pilot study to assess the effect of three short2ter) treat)ents on fre8uent and>or prolonged bleeding co)pared to placebo in (o)en using 4)planon. 0um .eprod 2 &A "'D 2%?:# 2.

:88!&5%,2 5!?!6/8M!&; /F C!U GU%5:&C!

.his /uidance (as developed by the $linical Effectiveness 5nit '$E5*D 5r Susan Brechin '5nit -irector*, 5r Madhuri ;ha9ur and Ms 6isa :llerton 'Research <ssistants* on behalf of the Faculty of Sexual and Reproductive Healthcare 'FSRH* in colla-oration .ith the Royal College of /-stetricians and Gynaecologists 0RC/G1 (ith a )ultidisciplinary group of health professionals co)prisingD 5r Sharon Cameron '$onsultant /ynaecologist, -ean .errace $entre and Royal 4nfir)ary of Edinburgh*, 8rofessor Hilary Critchley 'Professor of Reproductive =edicine, 5niversity of Edinburgh*, 5r Mehmet GaGvani '$onsultant /ynaecologist and Subspecialist in Reproductive =edicine and Surgery, Civerpool ;o)enFs Hospital>R$1/ /uideline and <udit $o))ittee Representative*, 5r :ilsa Ge--ie '$onsultant in $o))unity /ynaecology, Edinburgh>Hice2President of the FSRH and FSRH $ouncil Representative*, 5r :nna Graham 0/P, Horfield Health $entre, 9ristol>=e)ber of the FSRH $linical Effectiveness $o))ittee '$E$*6, 5r Hay Mc:llister '$onsultant in Sexual and Reproductive Health, .he Sandyford 4nitiative, /lasgo(*, 5r Haren 8iegsa '$onsultant in Reproductive Health, Forth Par7 Hospital, Eir7caldy* and 5r Mar9 Shapley '/P>Research Fello(, <R$ National Pri)ary $are $entre, Eeele 5niversity*. 4n addition, this /uidance docu)ent (as revie(ed by the FSRH $E$ and independently peer revie(ed by the follo(ing international peer revie(ersD 8rofessor Martha Hic9ey 'Professor of /ynaecology, School of ;o)enFs and 4nfantsF Health, 5niversity of ;estern <ustralia*, 8rofessor %an Fraser '-epart)ent of 1bstetrics and /ynaecology, 5niversity of Sydney* and 8rofessor Margaret Rees '$onsultant in =edical /ynaecology and Reader in Reproductive =edicine, 5niversity of 1xford*. Feedbac7 (as also received fro) 5r Maggie Cruic9shan9 'Senior Cecturer in /ynaecology 1ncology, <berdeen Royal 4nfir)ary>Representative for the 9ritish Society for $olposcopy and $ervical Pathology*. ;ritten feedbac7 (as received fro) Mr Sean 5uffy '$onsultant /ynaecologist, -epart)ent of 1bstetrics and /ynaecology, St Ma)esF 5niversity Hospital, Ceeds*, 5r Christina Fey 'FSRH $E$*, 5r !va Iungmann '$onsultant Physician in /5=>H4H, Condon*, 8rofessor Mary :nn 6umsden 'Head of Section, -ivision of -evelop)ent =edicine, /lasgo( Royal 4nfir)ary*, 5r Iames Mc?ic9er '$linical -irector, <bacus $linics for Sexual and Reproductive Health $are, Civerpool*, Ms Shelley Mehigan 'Nurse Specialist, FSRH $E$>.he /arden $linic, Sexual Health Services, 5pton Hospital, Slough*, Mrs 6ynn Hearton 'fpa user representative*, 5r Sarah Gray '/P>Pri)ary $are Cead in ;o)enFs Health, $orn(all and 4sles of Scilly P$.*, 5r :lison Bigrigg '-irector, Sandyford 4nitiative, /lasgo(* and 5r Ianet ilson '<ssociate Specialist in Sexual and Reproductive Health, 9elfast Health and Social $are .rust*. No co)peting interests (ere noted by )e)bers of the )ultidisciplinary group. <d)inistrative support to the $E5 tea) (as provided by Mrs Iane Carmichael. ;his C!U Guidance .as developed in colla-oration .ith the Guidelines Committee and approved -y the Standards Board of the RC/G> .he $E5 /uidance develop)ent process e)ploys standard )ethodology and )a7es use of syste)atic literature revie( and a )ultidisciplinary group of professionals. .he )ultidisciplinary group is identified by the $E5 for their expertise in the topic area and typically includes clinicians (or7ing in fa)ily planning, sexual and reproductive health care, general practice, other allied specialities, and user representation. 4n addition, the ai) is to include a representative fro) the FSRH $E$, the FSRH Education $o))ittee and FSRH $ouncil in the )ultidisciplinary group. Evidence is identified using a syste)atic literature revie( and electronic searches are perfor)ed forD =E-C4NE '$- 1vid version* '"%%&:2 8*A E=9<SE '"%%&:2 8*A Pub=ed '"%%&:2 8*A .he $ochrane Cibrary 'to 2 8* and the 5S National /uideline $learing House. .he searches are perfor)ed using relevant )edical sub3ect headings '=eSH*, ter)s and text (ords. .he $ochrane Cibrary is searched for syste)atic revie(s, )eta2 analyses and controlled trials relevant to unscheduled bleeding. Previously existing guidelines fro) the FSRH 'for)erly the Faculty of Fa)ily Planning and Reproductive Health $are*, the Royal $ollege of 1bstetricians and /ynaecologists 'R$1/*, the ;orld Health 1rganiNation ';H1* and the 9ritish <ssociation for Sexual Health and H4H '9<SHH*, and reference lists of identified publications are also searched. Si)ilar search strategies have been used in the develop)ent of other national guidelines. Selected 7ey publications are appraised using standard )ethodological chec7lists si)ilar to those used by the National 4nstitute for Health and $linical Excellence 'N4$E*. <ll papers are graded according to the /rades of Reco))endations <ssess)ent, -evelop)ent and Evaluation '/R<-E* syste). Reco))endations are graded as in the table belo(, using a sche)e si)ilar to that adopted by the R$1/ and other guideline develop)ent organisations. .he clinical reco))endations (ithin this /uidance are based on evidence (henever possible. Su))ary evidence tables are available on re8uest fro) the $E5. <n outline of the /uideline develop)ent process is given in the table on the inside bac7 cover of this /uidance docu)ent. Feedbac7 on /uidance docu)ents should be directed to the $E5 via e2)ail at ceu.)e)bersSggc.scot.nhs.u7.
6evel of evidence 4a 4b 44a 44b 444 4H !vidence Evidence obtained fro) )eta2analysis of rando)ised trials Evidence obtained fro) at least one rando)ised controlled trial Evidence obtained fro) at least one (ell2designed controlled study, (ithout rando)isation Evidence obtained fro) at least one other type of (ell2designed 8uasi2experi)ental study Evidence obtained fro) (ell2designed non2experi)ental descriptive studies, correlation studies and case studies Evidence obtained fro) expert co))ittee reports or opinions and>or clinical experience of respected authorities

Grades of Recommendations < 9 $ Evidence based on rando)ised controlled trials Evidence based on other robust experi)ental or observational studies Evidence is li)ited but the advice relies on expert opinion and has the endorse)ent of respected authorities /ood Practice Point (here no evidence exists but (here best practice is based on the clinical experience of the )ultidisciplinary group

SUMM:R< 8/%&;S

SUMM:R< 8/%&;S F/R ;H! M:&:G!M!&; /F /M!& US%&G H/RM/&:6 C/&;R:C!8;%/& H/ 8R!S!&; %;H U&SCH!5U6!5 B6!!5%&G
8R!*M!;H/5 C/U&S!66%&G

9efore starting hor)onal contraception, (o)en should be advised about the expected bleeding patterns both initially and in the longer ter).

%&%;%:6 M:&:G!M!&;

< clinical history should be ta7en fro) (o)en using hor)onal contraception (ith unscheduled bleeding to identify the possibility of an underlying cause. Hor)onal contraceptive users (ith unscheduled bleeding (ho are at ris7 of sexually trans)itted infections 'i.e. those aged G2? years, or (ho have a ne( sexual partner, or )ore than one partner in the last year* should be tested for Chlamydia trachomatis as a )ini)u). .esting for Neisseria gonorrhoeae (ill depend on sexual ris7 and local prevalence. ;o)en using hor)onal contraception (ho have unscheduled bleeding (ho are not participating in a National $ervical Screening Progra))e should have a cervical screen. < pregnancy test is indicated for (o)en using hor)onal contraception (ith unscheduled bleeding if the clinical history identifies the possibility of incorrect )ethod use, drug interactions or illness, (hich )ay lead to )alabsorption of oral hor)ones.

!,:M%&:;%/& :&5 %&?!S;%G:;%/&

Providing there has been consistent and correct use of hor)onal contraception a speculum examination should be perfor)ed for (o)en using hor)onal contraception (ith unscheduled bleeding if they haveD persistent bleeding or a change in bleeding after at least # )onths use of a )ethodA or failed )edical treat)entA or if they have not participated in a National $ervical Screening Progra))e. 4n addition, a -imanual examination should also be perfor)ed for (o)en using hor)onal contraception (ith unscheduled bleeding if they have other sy)pto)s 'such as pain, dyspareunia and heavy bleeding*. 4n general, an endometrial -iopsy )ay be considered in (o)en aged ,!? years 'or in (o)en aged G!? years (ith ris7 factors for endo)etrial cancer such as obesity, polycystic ovarian syndro)e, ta)oxifen use or unopposed estrogen therapy* (ho have persistent unscheduled bleeding 3 or more months after starting a )ethod or (ho present (ith a change in bleeding pattern. .he role of structural abnor)alities 'such as uterine polyps, fibroids or ovarian cysts* as a cause of unscheduled bleeding is li)ited. Nevertheless, for all (o)en using hor)onal contraception (ith unscheduled bleeding, if such a structural abnor)ality is suspected a transvaginal ultrasound scan andFor hysteroscopy )ay be indicated.

;H!R:8!U;%C M:&:G!M!&; /8;%/&S

4t is not generally reco))ended to change a co)bined oral contraceptive pill '$1$* in the first # )onths of use as bleeding disturbances often settle in this ti)e. Ho(ever, a $1$ (ith the lo(est dose of ethinylestradiol 'EE* to provide good cycle control should be used and the dose of EE can be increased to a )axi)u) of #? -g to provide good cycle control. 9leeding is co))on in the initial )onths of progestogen2only )ethod use and )ay settle (ithout treat)ent. 4f treat)ent )ay encourage (o)en to continue (ith the )ethod it )ay be considered. .here is no evidence that changing the type and dose of progestogen2only pill (ill i)prove bleeding but this )ay help so)e individuals. For (o)en (ith unscheduled bleeding using a progestogen2only in3ectable, i)plant or intrauterine syste) (ho (ish to continue (ith the )ethod and are )edically eligible, a $1$ )ay be used for up to # )onths 'this can be in the usual cyclic )anner or continuously (ithout a pill2free interval*. For (o)en using a progestogen2only in3ectable contraceptive (ith unscheduled bleeding, )efena)ic acid ? )g t(ice daily 'or licensed up to three ti)es daily* for ? days can reduce the length of a bleeding episode but has little effect on bleeding in the longer ter).

+ ** FSRH 2

+ FSRH 2 ** %

5%SCUSS%/& 8/%&;SFJK:s

5iscussion 8oints for Management of Unscheduled Bleeding in Using Hormonal Contraception

;he follo.ing discussion points have -een developed -y the FSRH !ducation Committee> 5iscussion 8oints "

omen

< 2#2year2old (o)an (ho has been ta7ing the co)bined pill for several years co)plains of brea7through bleeding in the last fe( )onths of pill use. ;hat 8uestions are you going to as7 her to help ascertain the cause of this recent change of bleeding patternR < 2?2year2old (o)an (ho has had 4)planonK for " year co)plains about the irregular spotting she has al(ays experienced (ith 4)planon. She (ishes to control the bleeding (hile on holiday for her honey)oon. ;hat treat)ents )ight be helpful to control the bleeding patternR < !&2year2old (o)an (ho has ta7en the progestogen2only pill for the last ? years suddenly develops heavy irregular bleeding. ;hat investigations (ould you need to considerR

Juestions for Management of Unscheduled Bleeding in Hormonal Contraception

omen Using

;he follo.ing 7uestions and ans.ers have -een developed -y the FSRH !ducation Committee> Indicate your answer by ticking the appropriate box for each question " ;o)en aged G2? years (ith unscheduled bleeding on the co)bined pill should have a high vaginal s(ab perfor)ed to exclude Chlamydia trachomatis. 4t is )andatory to perfor) a cervical s)ear in the presence of unscheduled bleeding (ith 4)planonK. .hree )onths of a progestogen2only pill can help settle unscheduled bleeding in users of in3ectable progestogens. .here is no evidence that (o)en ta7ing hor)onal contraception consistently and correctly have a higher ris7 of pregnancy if they experience unscheduled bleeding. Neisseria gonorrhoeae is a co))on cause of unscheduled bleeding (ith the co)bined pill in the 5E. <bdo)inal ultrasound is an i)portant tool in the detection of sub)ucous fibroids and endo)etrial polyps. )g t(ice daily* (as helpful in reducing bleeding episodes in (o)en using in3ectable progestogens during clinical trials. 9iphasic and triphasic co)bined pills are associated (ith an i)proved bleeding pattern co)pared to )onophasic pills. .he contraceptive patch is less li7ely to cause unscheduled bleeding than a standard co)bined pill preparation. < pill containing ? -g ethinylestradiol should be prescribed if a (o)an has persistent bleeding on a lo(er dose preparation and no cause for the bleeding can be found. True False

&

B =efena)ic acid '?

"

5nswers

+ */ FSRH 2

+ FSRH 2 */ %

&/;!S

+ FSRH 2

"#

&/;!S

*0

+ FSRH 2

&/;!S

+ FSRH 2

"?

&/;!S

*1

+ FSRH 2

S;!8S %&?/6?!5 %& ;H! 5!?!6/8M!&; /F C!U GU%5:&C!

S;!8 For)ulation of 9ey clinical 7uestions by the $linical Effectiveness 5nit '$E5*. Systematic literature revie. involving searching electronic, bibliographic databases by $E5 researchers. /-taining and revie.ing copies of the full papers of all relevant publications identified through the searches. Formal= critical appraisal of 7ey papers and develop)ent of short evidence tables. 5raft /ne Guidance docu)ent is (ritten, providing reco))endations and good practice points based on the literature revie(. Multidisciplinary Group Meeting co)prising sta7eholders and including service user representation, representation fro) the Faculty of Sexual and Reproductive Healthcare 'FSRH* Education $o))ittee and, (here possible, representation fro) the FSRH $linical Effectiveness $o))ittee '$E$* and FSRH $ouncil. . 8reparation of 5raft ;.o Guidance document based on discussion at the =ultidisciplinary /roup. 8eer Revie. of 5raft ;.o Guidance document by the =ultidisciplinary /roup and the FSRH $E$. <ll .ritten feed-ac9 on the 5raft ;.o Guidance document is tabulated and the $E5 response to these co))ents outlined. 5raft ;hree Guidance document is prepared based on (ritten feedbac7 and is sent to the =ultidisciplinary /roup and the FSRH $E$. 4n addition, t(o independent peer revie(ers are identified by the $E$ to provide feedbac7 at this stage. .he Final Guidance document is published by the FSRH. 1nly )inor co))ents can be accepted at this stage. .he $E5 has overall responsibility for (riting the /uidance docu)ent. .he =ultidisciplinary /roup and other peer revie(ers should highlight inconsistencies and errors or (here the text is inco)prehensible. < one2day )eeting held in /lasgo( (ith the =ultidisciplinary /roup to discuss the -raft 1ne /uidance docu)ent. ;%M! ;:H!& .his process )ust be co)pleted in a )axi)u) of 8 (ee7s.

.he =ultidisciplinary /roup )eeting is held at least 2 )onths before the /uidance deadline to allo( ti)e for develop)ent of further drafts.

Proofreading of the /uidance docu)ent is then perfor)ed by three )e)bers of the $E5 tea) independently and co))ents collated and sent bac7 by the 5nit -irector. < pdf version of the /uidance is available on the FSRH (ebsite.

C/MM!&;S :&5 F!!5B:CH /& 8UB6%SH!5 GU%5:&C!

<ll co))ents on published /uidance can be sent directly to the $linical Effectiveness 5nit '$E5* via e2)ail 'ceu>mem-ersLggc>scot>nhs>u9*. Oou (ill receive an auto)ated ac7no(ledg)ent on receipt of your co))ents. 4f you do not receive this auto)ated response please contact the $E5 by telephone 0 "!" 2#2 8!?%>8!& 6 or e2)ail 'ceu>mem-ersLggc>scot>nhs>u9*. .he $E5 is unable to respond individually to all feedbac7. Ho(ever, the $E5 (ill revie( all co))ents and provide an anony)ised su))ary of co))ents and responses (hich, after revie( by the $linical Effectiveness $o))ittee, (ill be posted on the Faculty (ebsite '...>fsrh>org* at regular intervals.