Women’s Health Update Beverley Hall June 2012

Aims and Objectives Why Women’s Health? Emergency Contraception Menopause Practical HRT assessment

Emergency Contraception Angie needs EC Too busy to get to the doctors….ran out of pills last week UPSI 3-4 days ago (can’t be sure) Already has 6 children….can’t cope with any more what with a wedding to plan

When is EC needed? Condoms- imperfect use/failure COC- if 2 or more pills have been missed in the first week and there has been UPSI in this week or during previous pill free week. POP- >3h late (or >12hours late for cerazette) Depo- Late injection > 14w since last IUD/IUS- UPSI in 5 days before removal, expulsion of device, threads missing and ?location of device Interacting drugs

When in the cycle is the highest risk?

Management of a request for EC What do you need to know? -Possibility of implanted pregnancy -Timing of episode(s) of UPSI -LMP or withdrawal bleed (and therefore likely date of ovulation) -Potential drug interactions -Previous EC within this cycle -Medical eligibility -Discuss potential STIs -Was the sex consensual -Discuss ongoing contraception -Arrange further treatment/follow-up

Available Options CHOICE -Copper IUD -Ulipristal acetate (UPA) / EllaOne -Levonorgestrel (LNG) / Levonelle

Copper IUD Emergency IUD can be fitted within 5d of UPSI or 5d of earliest predicted ovulation (which ever longest) Copper toxic to ovum and sperm, inhibits fertilization If she is amenable to a Cu-IUD is there an easy pathway for referral at your surgery? Great ongoing contraception

Levonorgestrel (LNG) Precise MOA not understood, inhibits ovulation LNG taken prior to LH surge results in ovulatory dysfunction in the next 5d (by which point sperm are non viable) No good after ovulation has occurred. No better than placebo at suppressing ovulation when given immediately prior to ovulation.

Unipristal acetate (UPA) Primary MOA is to inhibit or delay ovulation The probability of conception peaks just before ovulation. EllaOne’s inhibitory effect on follicular rupture allow it to be effective in some women even when administered immediately before ovulation, even if LH levels have already begun to rise Some effect on endometrium but contribution to efficacy yet unknown

When in the cycle is EC effective? Ella-One Levonelle Cu-IUD

Efficacy related to MOA Hormonal methods -Pills delay or inhibit ovulation UPA>LNG (nb. does not give protection later in cycle and may just delay ovulation) -No evidence for effect after fertilization LNG no effect after ovulation, and efficacy decreases with time UPA no evidence of effect after ovulation, but no apparent decline in efficacy with time

IUD Low failure rate <1% IUD may prevent fertilization IUD inhibits implantation

Adverse Effects Oral hormonal -Nausea (<20%) -Vomiting (rare 1%) -Some delay to cycle IUD -Insertion related -Heavy bleeding if long term use

Contraindications? IUD Same contraindications as routine IUD insertion. Risk of STI, previous ectopic, age and nulliparity are not contraindications. LNG UKMEC advises there are NO medical contraindications to levonelle including breast-feeding UPA No current UMEC guidelines. Not recommended for women with severe asthma insufficiently controlled on steroids. Caution in women with liver disease, heriditary galactose intolerance/malabsoption. Breast-feeding not recommended for 36 hours after UPA.

Drug Interactions LNG and UPA Liver enzyme inducers- current use or use in last 28d -double dose levonelle (if Cu-IUD unacceptable) -UPA not recommended UPA Medications that raise gastric pH- PPIs, H2-antagonists, antacids Other hormonal contraception - Require additional 7 days precautions if re or quick starting COC/POP

Can EC be used more than once in 1 cycle? LNG can be used more than once in a single cycle As no suggestion not safe in pregnancy, can be used for a recent episode of UPSI even if there has been a previous episode outside treatment window (120 hours) UPA should not be used more than once in a cycle. Limited data of safety in pregnancy therefore not recommended with multiple UPSI outside 120 hours. If IUD declined can give LNG for another episode of UPSI after UPA previously used.

Advice regarding future Contraception Neither LNG or UPA will provide contraceptive cover for subsequent acts of UPSI Ongoing contraception should be discussed Women may wish to exclude pregnancy before starting LT contraception but some ‘quick start’ methods are supported COC, POP or implant are suitable. Depo only if other methods not accetable. Mirena should not be used until pregnancy excluded.

Women already using contraception- Recommendations for additional contraception/ abstinence LevonelleElla-One COC7 days14 days POP2 days9 days Qlaira9 days16 days

Aftercare Follow up if require a pregnancy test, STI screening, Cu-IUD removal or have any concerns of difficulty with their contraception. If continuing with Cu-IUD as LARC then a check after their first period is advised. Failure of an emergency Cu-IUD should be managed as per FSRH guidelines on interuterine contraception. Pregnancies arising from failed oral EC need to be managed differently from other pregnancies. If a woman decides to continue with her pregnancy aster taking Ella-One then this should be reported to the manufacturer for inclusion on the European register to monitor outcomes.

Miss VP Requesting emergency contraception- UPSI 2 days ago No space for more babies! What else do you want to know?

Questions?

Menopause & Practical HRT

Menopause definition -If >50 years defined as 1 year since LMP -If <50 years defined as 2 years since LMP -Can take several years to go through menopause completely -Average age in the UK is 52 -Menopause said to be early if <45

Symptoms -About 8 in 10 women develop symptoms at some point -About 1 in 10 women seek help from their doctor Short term symptoms -Hot flushes: 3 in 4 women. -Sweats -Other symptoms: headaches, tiredness, irritability, poor sleep, depression, anxiety, aches & pains, loss libido. Basically everything! Long term symptoms -Skin and hair changes -Genital changes -Osteoporosis risk -Cardiovascular disease

Investigations -Clinical diagnosis -General blood tests may be useful when excluding other causes -Hormonal blood tests useful if suspected early menopause or previous hysterectomy so no periods -Don’t make my mistake!

Management Lifestyle -Regular sustained aerobic exercise, cooler clothing, reduce stress, coffee/alcohol/spicy foods may make flushes worse. -Encourage healthy diet (with enough calcium and Vit D) and stopping smoking improve CVD risk and osteoporosis risk. SSRIs and SNRIs -Several years ago noticed that menopausal women on these medications had few hot flushes. MOA unclear. 1-2 week trial is enough to see if helpful. No drug preferential. Clonidine Thought to work by interfering with noradrenaline which is involved with the process of sweating. Lots of SE’s dry mouth, dizziness so not commonly used. Worth a try if other treatments don’t help.

Complementary Treatments Due to concerns about safety regarding HRT over the past few years, many women have turned to complementary treatments. The following have been marketed for menopausal symptoms: black cohosh, red clover, dong quai, evening primrose oil, ginseng, soy and kava. There is concern about alternative treatments mainly surrounding potential drug interactions, as well as possible oestrogenic compounds which is a worry for women with oestrogen dependant cancers and the lack of quality control of production. Consequently these options are not recommended by NICE or the British Menopause Society.

Non-HRT treatments for vaginal dryness Vaginal lubricants are available from pharmacies without prescription which ease vaginal dryness. Some women only notice dryness during sex. Replens MD and Sylk are acidic, non-hormonal vaginal moisturisers available on prescription. Effects of these can last for up to 3 days and can be used as required. They can be used in addition to topical oestrogen if required.

HRT prescribing trends Women’s Health initiative lead to dramatic reduction in the prescribing of HRT Study looked at nearly 17,000 healthy post-menopausal women (aged 50-79) with an intact uterus. Randomized to HRT or placebo. Initial analysis of data showed worrying increased risk of VTE, stroke and breast cancer but this included women who had been on HRT for over 10 years and women in their 70’s! Re-assessment of this data has shown things have changed over the past 10 years and that ‘rational use of HRT initiated near the menopause’ is considered safe and acceptable.

HRT Prescribing Is she menopausal? Does she have any contraindications to HRT? Risks Vs Benefits If menopausal with no contraindications-is she having regular frequent cycles or not? Does she have a uterus? What are her main complaints? (systemic vs urogenital)

HRT Risks Breast Cancer Current opinion is that combined HRT taken for less than 5 years does not significantly increase the risk of breast cancer but studies have shown that after 5 years of use, there is an association with a small increased risk. Oestrogen only HRT is not thought to increase risk. Collaborative Group on Hormonal Factors in Breast Cancer. Breast Cancer and HRT: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997; 350: Years of HRTNo. of cases of breast cancer/1000 women aged No. of extra cases per 1000 women Less than 5450 More than 5472 More than More than

VTE risk Small increased risk. Again when data was analysed for healthy, normal BMI women aged the risk was negligible. If higher risk but HRT still felt to be of benefit then transdermal preparations may be more suitable. Cardiovascular disease Best avoided in patients with established CVD. Some suggestion of a ‘window of opportunity’ whereby, if HRT is commenced early, it may be beneficial not only for control of symptoms and prevention of osteoporosis, but also prevention of heart disease but if commenced later when disease of the blood vessels has developed, further damage may occur. Risk of endometrial cancer Minimal provided unopposed oestrogen not given Risk of ovarian cancer LT used associated with small increased risk.

Contraindications Pregnancy Undiagnosed abnormal vaginal bleeding Active or recent blood clot or myocardial infarction Suspected or active breast or endometrial cancer Active liver disease with abnormal liver function tests Porphyria cutanea tarda

Type of HRT Uterus?Peri-menopausalPost-menopausal YesCyclical CombinedContinuous Combined NoOestrogen only HRT is available as tablets, skin-patches, gels, nasal spray or implants. There are several different brands for each of these types of HRT. All deliver a set amount of oestrogen. Taking unopposed oestrogen increases chance of abnormal endometrial proliferation. Therefore, oestrogen in HRT is usually combined with a progestogen hormone. In many HRT products the oestrogen and progestogen is combined (in the patch, implant etc), but they can be taken separately. Women without a uterus do not require a progestogen. Mirena coil is suitable for supplying the progestogen component of HRT- also benefits from contraceptive properties and reduced menstrual blood loss.

Topical Oestrogens TabletPessaryCreamRing Small, easy to insert, licensed for LT use Larger, easy to insert, licensed for 3-6 months Helpful if vulval irritation but can be ‘messy’. Licensed for 3- 6months Vaginal ring that remains in place for 3 months. Licensed 2 years Nightly for 2 weeks then twice weekly Changed 3 monthly Vagifem Vagifem 10 OrthogynestGynest and Ovestin Estring There is no problem with topical oestrogen for patients with previous oestrogen dependent cancers.

Prescribing HRT Start low and go slow……(referring to oestrogen dose) Decide whether oestrogen only, cyclical combined or continuous combined Decide on route of administration (higher risk for VTE, bowel absorption problems or hx migraine may benefit from patch) Patches can be matrix or reservoir (matrix causes less irritation & adhere better) Gels useful if you want topical but patches irritate skin Look in the BNF (there are hundreds to choose from!) Get familiar with a few brands Examples: -Oestrogen only: Elleste-Solo (1mg or 2mg), Premarin (0.3, 0.625, 1.25mg) -Cyclical combined: Elleste-Duet, femoston -Continuous combined: Femoston Conti (low dose) Ellest-Duet Conti (high dose)

Tibolone 2.5mg daily Gonadomimetic synthetic preparation with weak estrogenic, progestogenic & androgenic properties. Because of its androgenic component, Livial can be particularly helpful for postmenopausal patients with reduced libido. Minimal increased breast cancer risk- similar to oestrogen only HRT.

Making changes Try to give a 3 month trial before making changes to HRT treatment If menopausal symptoms insufficiently controlled consider increasing oestrogen Side-effects usually due to the progestogen- consider decreasing dose or changing type. Cyclical combined HRT causes a monthly bleed in about 85% of women. If the periods are becoming infrequent, the progestogen can be taken for 2 weeks every 3 months, inducing a 3 monthly bleed (long cycle HRT e.g. Tridestra). Continuous combined HRT may cause spotting in the first 6 months but shouldn’t thereafter. Always investigate any abnormal bleeding. Changing from cyclical to continuous HRT- when >54 or LMP >12months

Review If commencing or changing therapy see every 3 months If settled- see for annual review -Symptom control -Side-effects -Review duration -Assess risks and benefits -Check BP

Stopping treatment Symptom relief 3-5 years then gradually withdraw (no set method, if on high dose reduce to lower dose for 2-3 months then stop) If symptoms recur, restart- no arbitrary limits. However, short recurrence of symptoms for 2-3months is common after cessation- this usually soon settles. Try to persist. Is it mainly uro-genitial now? Perhaps topical treatments would do. Osteoporosis prevention (not first line) 5-10 years minimum? Premature menopause Treat to average age of menopause

Mrs P 51 year old lady Complaining of hot flushes ++, sweats at night time What do you want to know? Do you examine? Any investigations? What do you suggest? When will you see her again?

Useful Resources

Questions?