LARC problems - WMCASH

LARC problems

Dr Diana MansourConsultant in Community Gynaecology

Newcastle upon Tyne

Declaration of interests

• I have received financial support to attend pharmaceutical advisory boards, speaking at educational meetings/webinars/conferences, undertaking scientific research from Bayer, Consilient Healthcare, HRA Pharma, MSD, Mithra, Mylan, Pfizer and Vifor Pharma

• I am FSRH Vice-President, Clinical Quality

•All my clinical work is for the NHS

Can women access LARCs?

• LARC provision • Reduced activity in primary care• Back on target for IUCs in community

services but less requests for implants

• Solutions for improved provision post-COVID• Commissioning changes with Integrated

Care Systems• Appropriate payment for primary care• Easily accessible LARC education• What about the young and ‘vulnerable

groups?

Number of abortions, England and WalesJanuary to June 2019 and 2020

https://www.gov.uk/government/statistics/abortion-statistics-during-the-coronavirus-pandemic-january-to-june-2020

Interpregnancy intervals and importance of immediate postpartum contraception – local audit by Dr Kaia Scurr

• Short inter-pregnancy intervals (IPIs) associated with elevated risk of maternal and perinatal mortality

• IPIs <12 months increased risk of

• low birth weight

• small size for gestational age

• pre-term delivery

•WHO/RCOG recommend IPI >2 years

Scurr K at al. Winning poster, Virtual FSRH meeting Autumn 2020




• In the UK, 1 in 13 abortions occur within 1 year of a previous birth

• In Newcastle, 1 in 5 are within 1 year of a previous birth

• Postnatal audit

• No women wanted to conceive again within the next year

• Only 1/3 felt informed about their PNC choices

• Most women planned to get PNC from their GP at ‘postnatal’ check

• >50% would have been interested in receiving PNC prior to discharge

• At last desogestrel POP on the postnatal ward………


Confusion about extended use in LARCs during Covid pandemic• How long will FSRH extended use guidance last for?

• Levosert IUS now licensed for 6 years use for contraception and HMB

• Mirena IUS can be used up to 6 years for contraception• ?HMB

• ?endometrial protection for ERT

• No change for Jaydess or Kyleena

• Standard banded copper 380 IUDs up to 12 years• All other copper IUDs as indicated by their summary of

product characteristics

Mirena SPC change in December 2020

• Contraceptive efficacy of Mirena has been studied in 5 major clinical studies with 3330 women using Mirena • Failure rate (Pearl Index) approximately 0.2% at 1 year and cumulative failure

rate approximately 0.7% at 5 years

• In another clinical study to evaluate contraceptive efficacy of Mirena during extended use beyond 5 years, failure rate during Year 6 was 0.29% (Year 6 Pearl Index 0.35). The failure rate also includes pregnancies due to undetected expulsions and perforation. • Similar contraceptive efficacy has been observed in a large post-marketing

study with more than 17000 women using Mirena

Question 1. Can 52mg LNG IUS be used for emergency contraception?1. Yes

2. No

3. Haven’t a clue

IUD or IUS for emergency contraception?

• 355 women randomised to 52mg LNG IUS and 356 to T380A IUD• 290 IUS and 300 IUD users had urine pregnancy test at one month

• Pregnancy rates 1 in 317 IUS (0.3%; 95% CI 0.01 to 1.7) and 0 in 321 IUD group (0%; 95% CI, 0 to 1.1) • between-group absolute difference in both analyses was 0.3 percentage

points (95% CI, −0.9 to 1.8), consistent with the non-inferiority of IUS to copper IUD

• Adverse events where participants sought medical care in first month after placement • 5.2% in IUS and 4.9% in IUD group

Turok et al N Eng J M 2021

Question 2. What are the most common problems with LARCs?

1. Bleeding problems

2. Mood changes/loss of libido

3. Problems at insertion site

4. Reversibility

5. No problems

Question 3. Do women using Sayana Press bleed more than those given Depo Provera?1. Yes

2. No

3. Haven’t a clue

Bleeding problems with injections• Depo-Provera IM

• Amenorrhoea up to 30% in first 3 months, 55% by month 12• Irregular bleeding and spotting• prolonged (>10 days) episodes up to 33% in first 3 months decreasing to 12% by

month 12

• Sayana Press SC• Amenorrhoea up to 26.5% in first 3 months, 56.5% by month 12• Irregular bleeding and spotting

Sayana Press and Depo-Provera SmPC 2020

Bleeding pattern with DMPA

• Decreased incidence of irregular bleeding with time

• No consistent differences in bleeding pattern according to:• Age

• BMI

• Percentage of subjects shifting from bleeding and/or spotting to amenorrhoea • increase with each subsequent injection

Arias RD et al. Contraception 2006

Management of bleeding in injection users

• Exclude pathology

• Reassure, prolonged irregular bleeding will decrease with time

• Reduce injection interval?

• Treatment for bleeding problems may occur in 0.5-4 occasions per 100 women years of use• Low dose (30 mcg ethinylestradiol) combined oral contraceptive pill

• Estrogen replacement therapy such as conjugated equine oestrogen (0.625-1.25 mg daily)

• Estrogen therapy may need to be repeated for 1-2 cycles

Depo-Provera SmPC 2020

Bleeding patterns with the different levonorgestrel-releasing IUSs

Gemzell-Danielsson et al. 2012

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Kyleena®:Bleeding days

Jaydess®:Bleeding days

Mirena®:Bleeding days

Spotting-only days Spotting-only daysSpotting-only days

Managing bleeding with 52mg LNG IUS

• Recent systematic review• 6 RCTs and 2 prospective cohort studies

• What are the results?• Naproxen may be effective for prophylactic

treatment of immediate bleeding post fitting (<12 weeks)

• Oestradiol in treating ongoing bleeding (>6 months)

Van der Heijden et al. Eur J Contracept Reprod Health Care 2020

Size of copper intrauterine devices (IUD) may matter

Hannat Akintomide et al. BMJ Sex Reprod Health 2019;45:263-268

Continuation of copper IUDs in users under 30 years at 1 year (about 5800 women from EURAS study)

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copper surface area IUD shape/design IUD width in mm IUD arms flexibility

p=0.008 p=0.024 p=0.872 p= 0.005

Akintomide et al – in press Eur J Contracept Reprod Health

Ballerine – the IUB

• Smaller version

• 28% expulsion rate at 12 months

• Pregnancy rate no better

• Side effects similar although makers claim less period pain

• Medium size device now available (can prescribe on FP10)

• but no published data

• More expensive than other copper IUDs (£38)

Weibe & Trussell Contraception 2016

What do we tell potential implant users about bleeding?

• Unpredictable and irregular bleeding patterns are common in implant users• If you get very little bleeding initially this is likely to continue

• If you have frequent (more than once a month) and/or prolonged bleeding (more than 2 weeks) - 40% this bleeding will settle in next 3 months

• Bleeding can vary over 3 year period• Some days you may bleed and other days it will stop

• Bleeding tends to be lighter than a period

• Bleeding patterns may change when implant is replaced

• No effect of parity, BMI on bleeding pattern

Mansour et al. Eur J Contracept Reprod Healthcare 2008

Guidance for managing bleeding with ENG implant?

• Treatment options to stop a bleeding episode include:• Continuous or cyclically CHC (pill, patch or ring)

for 3 months (outside of the product licence) but could be used long term

• Tranexamic acid 500mg twice daily for 5 days

• Ibuprofen 400mg up to 3 times a day for 5 days

Guidance for managing bleeding with ENG implant?

• Treatment options to stop a bleeding episode include:• Anecdotally one desogestrel POP daily or

therapeutic doses of progestogen for up to 3 months

• NETA 5mg or medroxyprogesterone acetate 10mg up to 3 times a day continuously or for 21 days with a 7 day break

• No evidence that these treatments confer a long term benefit

Mood change/loss of libido with LARCs

Nocebo effect

• Harmful, unpleasant, or undesirable effect • after receiving an inert drug or placebo

• Symptoms related to ‘expectation of outcome’ • power of suggestion

Nocebo in practice• Asthmatics given nebulized ‘irritant’

• 48% experienced increased airways resistance

• Independent of risk factors (Framlingtonstudy) women who believed they were at increased risk of myocardial infarction• Nearly four times as likely to die of coronary

heart disease

• Sham electrical currents caused headache in over 2/3rds college students

Haln RA. Prev Med 1997; Schweiger & Parducci J Biol Sci 1981

‘Background’ noise of non-specific complaints

• Background prevalence (German medical students)• 65% fatigue• 30% nasal congestion• 25% headache• 13% muscle pain• 12% joint pain • 9% irritability• 11% free of symptoms

• More common in women than men

Meyer et al. Clin Pharmacol Ther 1996

In vivo release rates of levonorgestrel-releasing contraceptives

Hofmann BM et al. Eur J Contracept Reprod Health Care December 2020

Total serum concentrations of levonorgestrel from an LNG COC, POP and implant


Total serum concentrations of levonorgestrel from a POP, implant and Mirena


Total serum concentrations of levonorgestrel from Mirena, Kyleena and Jaydess


Depression and hormonal contraception

• Just over 1 million women • mean age, 24.4 years• mean follow-up time 6.4 years

• Compared with nonusers of contraception, relative risk of first use of antidepressant• COC RR 1.23 (95% CI, 1.22-1.25)• POP RR 1.34 (95% CI, 1.27-1.40)• LNG-IUS RR 1.4 (95% CI, 1.31-1.42)• Relative risks generally decreased with increasing age• No data for implants, injectables or copper IUDs

Skovlund et al. JAMA Psychiatry 2016

Depression and hormonal contraception

• A review found minimal association between progestogen-only methods and depression in general population

• Adverse mood effects of hormonal contraceptives more consistent • If there is a previous history of depressive

symptoms

• and/or negative experience with hormonal contraception

Lewis et al. Current Psychiatric Reports 2019

Question 4. Does hormonal contraception cause loss of libido?1. Yes

2. No

3. No idea

Loss of libido and contraceptive methods

• 1,938 of Contraceptive CHOICE participants surveyed at baseline and 6-month• 23.9% reported lacking interest in sex at 6 months after starting new method

• Of 262 copper IUD users 18.3% reported lacking interest in sex

• Loss of interest in sex more prevalent • in young (younger than 18 years: adjusted OR 2.04)

• in black population (adjusted OR 1.78)

• in married/living with partner (adjusted OR 1.82)

Boozalis et al. Obstet Gynecol 2016

Loss of libido and contraceptive methods

• Compared with copper IUD users loss of interest in sex more prevalent in• Depot medroxyprogesterone (adjusted OR

2.61, 95% CI 1.47-4.61)

• Vaginal ring (adjusted OR 2.53, 95% CI 1.37-4.69)

• Implant (adjusted OR 1.60, 95% CI 1.03-2.49)

• No association with LNG IUS, oral contraceptive pill and patch

Boozalis et al. Obstet Gynecol 2016

Problems at insertion site

• DMPA IM• Pain, haematoma formation, infection, nerve damage, rarely anaphylaxis

• DMPA SC• Skin dimpling, lipodystrophy, no reports of anaphylaxis

• Implant• Pain, infection, expulsion, scarring, deep placement, paraesthesia,

translocation

• IUD/IUS• Pain with fitting, infection, misplacement, perforation, non-visible threads

Reversibility of LARCs

• Prospective cohort study, Denmark and North America

• 17 954 women using the following contraception• 38% (n=6735) oral contraceptives

• 13% (n=2398) LARCs

• 31% (n=5497) barrier methods

• Compared with barrier method users• Pill, vaginal ring, and some LARC users

experienced short delays in return of fertility

Yland et al. BMJ 2020

Reversibility of LARCs

• Delay to return to fertility compared to barrier users• Injectables – delay of 5 to 8 menstrual cycles

• Patch – delay of 4 cycles

• Pill and vaginal ring – delay of 3 cycles

• Hormonal IUS and copper IUD users• Delay of 2 cycles

• Implant contraceptives • Delay of 2 cycles

• Lifetime length of use of hormonal contraceptive methods was not associated with a change in fecundability

Yland et al. BMJ 2020

Learning points

• Keeping up to date in these pandemic times can be difficult, my ‘go to’ websites• FSRH website

• Primary Care Women’s Health forum

• Remember the ‘nocebo’ effect• Only talk about known side effects…..

• Handling complex patients during COVID• Ask your local SRH Lead/ask a colleague

• ‘Advice and Guidance’

• FSRH Members Evidence request

Documents

LARC problems - WMCASH