Essay 298 - HRT

A 52 year old woman (uterus in-situ) has been referred to the gynaecology clinic because of debilitating menopausal symptoms and worries about taking hormone replacement therapy. (a) Discuss and justify your clinical assessment [11 marks] (b) Discuss the steps that can be taken to minimize progestogenic side-effects associated with combined hormone replacement therapy [9 marks].

a.The initial clinical assesment should include detailed thorough history of type of menopausal symptoms, whether night sweats only, or other symptoms like dyspareunia, urine frequency urgency , also effect of symptoms on her Quality of life is important.duration and symptom severity is essential,.Most vasomotor symtoms don't persist more than 1-3 years. vaginal atrophy can be treated topically with estrogen.  also sexual history , whetehr sexualy active or not, dyspareunia and problems with libido should be assessed( may require Testosterone replacement ) .enquiry about other medical problems like Htn, DM, OR h/o previous stroke or thromboembolic events, inherited or acquired thrombophillias( which may contraindicate  estrogentic HRT ).Drug history and smoking history in addition to family history of any VTE events in first degree relative (SHE MAY BE OFFERED THROMBOPHILLIA SCREENING IF STRONG family history.The last st smear history is important.       clinical examination shoul include BP measurment, BMI ASESMENT and systemic review to exclude other medically relevant disease. pelvic examination if history reveal other assosiated symptom of prolapse or incontence or pelvic masses.                                      

Progestogenic side effects can be reduced by reducing the dose of progesterone used ( but taking care to use a dose effective in endometrial protection.changing the type of progestogen from 19 nortestosterone derivative to 17oh progesterone. sometimes changing the route of admistration whether subdermal, patches or using LNG ius may be effective.or using longer cycles evere 13 weeks instead of every 3 weeks or daily regimens. or using 10 days instead of 14 days progesterone. Sensitive and adequate pre- prescription is effective in improving patient syptom compliance especially if counselling based on evidenced based information. and follow up apointments to detect any complaints .

A.

I will enquire about historyof presentillnesslike severity of her symptoms and its effect on quality of life. Any other symptoms like vaginal dryness and night sweating should be enquired. Current medication that may increase risk of VTE should be rule out like; heart disease (ischemic, cardiomyopathy), renal diseases (nephrotic syndrome, renal impairment), autoimmune disease like SLE and inflammatory bowel disease.  As All these medical problems are additional risk factors for VTE with HRT.   The menstrualhistory includes date of LMP, to knowhow long she was menopausal. Past medicalhistory should be inquired in regard to, prior VTE, breast cancer and cardiovascular disease to make an informed decision regarding suitability of HRT or not. Familyhistory of VTE in first and second degree relatives, breast cancer and cardiovascular disease should be enquired to explore risks that may contraindicate HRT. Social history like smoking and drugs injection to asked.

In Examination, I will check her BP, BMI and Lower limbs for gross varicose veins. If she is asymptomatic, there is no need of any investigation. However if women has personal and family history of VTE, I will do her thrombophilia screening.

Routine blood test for CBC, LFT, and urea and electrolytes should be done before initiating HRT. Acquired and Hereditary thrombophilia screening tests not recommended as a routine, but it is recommended if there is strong family history or personal history of VTE.

B.

The progestogenic side effects include bloating, acne, mode swings and PMS like effect. Progesterone and dydrogesterone usually have lower side effect because of receptor specificity. Having the dose of progestogens to 10 days monthly may minimize progestogenic side effect. LNG-IUS can be inserted as it has minimal systemic progestogenic effect and confer protection against endometrial hyperplasia of systemic oestrogen therapy. The new generation of COCP like Yasmin, that contains drospirenone instead of progestogens may be prescribed. Non-hormonal treatment like SRRIs (fluoxetine), SNRIs (venlafaxine), clodnidine (alpha2 agonist) can be given as alternative to HRT to mitigate menopausal symptoms. 

(A)

Clinical assessment includes evaluation of main menopausal symptoms that is bothersome to the patient as alternatives to HRT can be considered. Systemic HRT is the most effective treatment for vasomotor symptoms, but vaginal atrophy can be relieved by lubricatns or local estrogens. I will ask if the menopausal symptoms affects her quality of life. I will ask for a personal and family history of breast cancer as the risk of creat cancer is inreased in HRT use of more than 5 years. I will ask for a personal or family history of venous thromboembolism as VTE risk is increased by 2-3 times especially in the first year of HRT use. I will ask for her menstrual history, whether she is menopausal or she is still having regular periods as the HRT regime is different (sequential combined HRT or low dose Combined oral contraceptive pills for premenopausal or continuous HRT for postmenopausal status). I will ask if she is sexually active and her current contraception as additional contraception may be required on top of HRT. I will ask for cardiovascular risk factors e.g. smoking, IHD, hypertension and hyperlipidemia as HRT is associated with an increased risk of cardiovascular event and stroke. I will ask her for any risk factors for osteoporosis e.g. prolonged steroid use, family history of osteoporosis, early menopause as HRT can confer additional benefit of prevention of osteoporosis. On examination, I will take her height and weight to assess her BMI and check her blood pressure with an appropriate size cuff. I will offer thrombophilia screen if she has a previous history or family history of VTE.

(B) I will explain the indication for a progestogen component in combined HRT and its rationale of preventing hyperplasia to enhance the patient's understanding of her treatment. Detailed counselling of the patient with regards to the side effects of progestogens including bloatedness, nausea and vomiting, water retention, acne, skin changes etc can facilitate tolerance and compliance. The side effects can be minimised by considering transdermal progesterone patch/implant or the LNG-IUS which exerts local progesterone effects with minimal systemic absorption as compared to the oral route. The duration of progesterone can be shortened from 14 days to 10 days per cycle; alternatively continuous regime of 3 cycles of HRT before a withdrawal bleed can be considered. Complementary alternative medications e.g. clonidine and phytoesttrogens as well as SSRIs can be considered instead of HRT for vasomotor syptoms. LIfestyle changes e.g. regular exercise, stopping smoking, healthy diet can improve overall well-being and mitigate the effects of progesterone if present.

a)       Timing of onset of menopause is to be obtained as it will guide us to what regime of hormonal replacement therapy(HRT) is recommended (if less than a year since LMP sequential is preferred over the continuous combined HRT). What menopausal symptoms is really bothering her is to be elicited as the treatment will be tailored according to specific symptoms. HRT is shown to be effective in treating hot flashes and night sweats and also for local use if suffering from urogenital symptoms like vaginal dryness leading to dyspareunia or urinary symptoms. Any personal or family history of DVT or thrombophilia is to be obtained as the risk of HRT might outweight the benefits in such cases (especially oral HRT). Any significant past history like breast cancer is to be asked as we have to be cautious and best avoided (as the risk of recurrence in long term increases but recurrence in short term is uncertain). Previous history of cardiovascular accident is also to be questioned as there has been shown increased incidence of coronary artery disease in the first year of  of use. Social history like smoking and drinking alcohol will be obtained as modification of such behaviors will be helpful in alleviating some of the symptoms and reduce overall risk. Any over the counter medication that has been tried is also elicited as some of it may have interaction with HRT if she is still using. On examination I will calculate her BMI, as obesity is associated with increase risk of DVT, which will increase the risk of HRT. Baseline Blood pressure is checked. Abdominal examination will be done to look for any masses as they need to be investigated before commensing any HRT. Vulval and vagina inspected for atrophy. Bimanual pelvic examination is done to note uterine size, tenderness and any adnexal mass.

b)        Usually those women who have uterus insitu require progesterone to be added to their HRT to prevent endometrial hyperplasia and cancers. Side effects of progestrones can be minimized by halving the dose and reducing the duration from 12-14 days to 7-10 days. This may however lead to bleeding problems and hyperplasia, hence there should be low threshold for investigating with scans and endometrial sampling if indicated.  Using LNG IUS is licensed in UK for 4 years to counteract the estrogen effect of combined HRT and minimize the progestogenic side effects as it is locally acting. Changing the type of progestogenic component of HRT may contribute in reducing the side effects like drospirenone which has antiandrogenic and antimineralocorticoid property has been incorporated with low dose estrogen in a continuous combined HRT. Patient information leaflet is given and follow up appointments arranged to detect any further complaints.

 A,  Severity of symptoms and its effects on quality of life should be enquired. Her knowledge about  HRT and her concerns about side effects should be explored so that adequate counselling about the benefits of short  term use of  HRT can be given. Type of symptoms should be asked,  Vaginal dryness and dyspareunia   can be treated with vaginal creams with minimal systemic side effects. History of personnel or family history of VTE should be asked  as use of HRT is associated with increased risk of VTE . History of cardiovascular disease or risk factors like obesity, hypertension and diabetes, smoking should be asked as HRT increases the risk  of cardiovascular diseases.History of personnel or family history of breast  cancer should be elicited. Her  LMP , previous use of contraception especially cocp and and problems associated with its use should be enquired .

 Bp and BMI should be measured.

B, Progestogenic side effects are fluid retention, moodswings,pms like symptoms and androgenic side effects like acne, hirsutism

These side effects can be minimised by reducing the dose of progestogen or duration of therapy for 7-10 days. problem with this is it may not provide adequate endometrial protection with risk of endometrial hyperplasia and endometrial cancer. So there should be low threshold for frequent follow up by TVUS and endometrial biopsy.

Type of progestin like dydrogesterone has minimal side effects.

Drospirenone  a spirinolactone antagonist which has anti androgenic and antiminerelocorticoid if combined with low dose estrogen can be used which has a better sideeffect profile

 A,  Severity of symptoms and its effects on quality of life should be enquired. Her knowledge about  HRT and her concerns about side effects should be explored so that adequate counselling about the benefits of short  term use of  HRT can be given. Type of symptoms should be asked,  Vaginal dryness and dyspareunia   can be treated with vaginal creams with minimal systemic side effects. History of personnel or family history of VTE should be asked  as use of HRT is associated with increased risk of VTE . History of cardiovascular disease or risk factors like obesity, hypertension and diabetes, smoking should be asked as HRT increases the risk  of cardiovascular diseases.History of personnel or family history of breast  cancer should be elicited. Her  LMP , previous use of contraception especially cocp and and problems associated with its use should be enquired .

 Bp and BMI should be measured.

B, Progestogenic side effects are fluid retention, moodswings,pms like symptoms and androgenic side effects like acne, hirsutism

These side effects can be minimised by reducing the dose of progestogen or duration of therapy for 7-10 days. problem with this is it may not provide adequate endometrial protection with risk of endometrial hyperplasia and endometrial cancer. So there should be low threshold for frequent follow up by TVUS and endometrial biopsy.

Type of progestin like dydrogesterone has minimal side effects.

Drospirenone  a spirinolactone antagonist which has anti androgenic and antiminerelocorticoid if combined with low dose estrogen can be used which has a better sideeffect profile

I would ask the woman when her last menstrual period (LMP) was. If her LMP was over a year ago she is classed as post menopausal, anything less than a year and she is peri menopausal and if she were to opt for HRT she would be advised to take sequential combined HRT where progesterone is taken only for 12-14 days per month as opposed to a continuous combined combination.  I would ask if she was on any current contraception, some forms of contraception such as the mirena may help with menopausal symtoms.

I would ask about her symptoms of the menopause as they can be treated with other medications if HRT is contraindicated or not wanted by the patient. Vasomotor symptoms such as hot flushes and night sweats can be treated with venlafaxine. Urogenital symtoms such as vaginal dryness, dyspareunia, urinary frequency, dysuria, nocturia can be treated with topical lubricants or oestrogen cream. Low mood and anxiety can be treated with antidepressants or cognitive behavioural therapy.

I would ask if she has had breast cancer or endometrial cancer, or if there is a family history of these cancers, as there is an increased risk of developing endometrial cancer and small risk of breast cancer with taking HRT. I would ask if she has had any past or current history  or if there is a family history of venous thromboembolism , or any thrombophilias as there is an increased risk of VTE with HRT and is contraindicated.

HRT has an increased risk of cardiovascular disease so I would ask about any cardiovascular problems such as stroke, hypertension, and diabetes mellitus.

I would ask if she has had any abnormal uterine bleeding as this will need to be investigated before starting any menopausal treatment.

I would ask about her lifestyle as exercise, healthy diet, normal BMI, low alcohol and caffeine intake have all been proven to be affective in reducing menopausal symptoms. I would advise on changing these if necessary.

I would ask what concerns she has about taking hormonal therapy and inform her of the relative risks of the therapy and give her information leaflets on it and alternative therapy to HRT.

I would check her BP and pulse to check for hypertension. I would examine her abdomen to check for pelvic masses.

b) HRT with progesterone (combined HRT) is required for patients who have a uterus still in situ as it reduces their risk of endometrial hyperplasia and cancer. It can cause side effects such as fluid retention, acne and hirsuitism and mood swings. In order to reduce these side effects, the progesterone dose can be halved and the duration can be shortened to 7-10days as opposed to continuous or 12-14days. This can result in bleeding and hyperplasia so there should be low threshold for investigation.

The progesterone can be taken in vaginal pessaries or gel which may help with reducing side effects from oral preparations .

A mirena coil can be inserted that releases continuous low dose progesterone, it is licensed for 4 years for progestogenic opposition of oestrogen.

Changing the type of progesterone may reduce the side effects experienced, progesterone and dydrogesterone tend to have fewer side effects due to their receptor specificity. 

A/

A general history including parity, smear history, age of menopause, LMP if still menstruating should be taken. Any past or current use of contraception should be established especially COCP/POP. 

It is important to ascertain the nature of her menospausal symptoms: is it vasomotor? (HRT will help with symptoms as will SSRIs), Is it loss of lidibo (in which case she may benefit from testosterone), is it vaginal atrophy (can be treated with vaginal oestrogen creams or pessaries). Ask if symptoms are affecting her quality of life and give opportunity to answer questions and discuss her concerns.

Any history of stroke/hypertension/ IHD & hyperlipidaemia should be established as the presence of these in conjunction with HRT increases risk of further heart disease/stroke. HRT increases the risk of breast cancer fi continued >5 years therfore establish any personal or family history of breast/cervical/ovarian/endometrial cancer. Ask about any history of osteoporosis as continuous combined HRT can reduce fracture risk of long bones however should not be started for this purpose. Discuss any personal or family history DVT/PE as well as any heretible/aquired thrombophilia as HRT associated with increased risk of thromboembolic event and should not be started in those with a previous history of DVT/PE or in those with a high risk  thrombophilia (antithrombin III). Thrombophilia screen should not routinely be done unless indicated by history.

Ascertain smoking/alcohol/exercise history and undertake BP, Height, weight and calculate BMI. Reduction in alcohol and smoking and increasing exercise may reduce symptoms. Check if she is using any 'over the counter remedies' as these may alreasy contain oestrogen and increase risk.

B/

Explain the importance on progesterone in HRT for endometrial protection. HRT should be used at the lowest dose for the minimum amount of time. Therefore it may be possible to reduce progesterone dose or swap to an alternate type of progesterone such as drosperidone, which may reduce fluid retention. In addition, progesterone may be used for only 10-14 days during the cyle to minimise effects, while stil protecting the endometrium. If the patient is still menstruating she could have a sequential continuous combined preparation therefore decreasing the number of days with progesterone in cycle. A Mirena IUS (Licensed for 4 years) can be used as the progesterone component on combined HRT and has less systemic effects. In addition, it can used with an oestrogen patch to reduce DVT risk. Ecourage healthly lifestyle, weight loss, exercise and reduction in alcohol and smoking. Arrange follow up to check symptoms and compliance with therapy and to check if the patient is taking it properly. Discuss alternatives to HRT including SSRIs, accupunture, homeopathy, phyto-oestrogens, clonidine.

Hrt  essay.

A)The aim of assessment is to address the  severity  of the symptoms ,interfering with her quality of life. The risks  and benefits of HRT are discussed, and her worries are explored. The women’s  vasomotor symptoms as well as other  associated symptoms  ( dyspareunia , urinary frequency, or stress incontinence due to estrogen deficiency, mood changes, depression) are assessed to give appropriate advice. Her last  menstrual period is enquired to asses her suitability for continuous  (If menopause is >2 years ,or sequential if <2 years)or sequential form of HRT. It is important to assess her risk factors for Venous thrombo embolism (VTE),a personal or first degree relative with history of VTE, should prompt a thrombophilia screen. Personal history of smoking is a risk for VTE. Personal history of Breast cancer, or a first degree relative with breast cancer is important (to advice her against HRT) , risk for ovarian cancer and endometrial cancer are assessed .A personal or a family history of cardiovascular disease is  important to advice regarding HRT,A personal or family history of osteoporosis will help to convey about the long term benefits of HRT. It is important to assess her Blood pressure and BMI as risks of HRT are more with high B.P. and morbid obesity. Investigations are usually not recommended unless there is a strong history suggestive of breast cancer or Venous thrombo -embolism . The benefits of HRT are conveyed to the women ,i.e. it helps to reduce  the debilitating  vasomotor symptoms ,benefits for mood swings, alleys depression, sexual pleasure is restored, dysparunia is reduced. On longterm use of HRT, there is reduction of osteoporosis and fractures , increases cognition , and reduces Alzimer’s disease , toothloss. The risks due to long term HRT i.e. for more than 5 years are breast cancer risk of 35/1000 and 51/1000( background risk is 32/1000 per year)if taken for 5 years and  15 years respectively is conveyed to her. The cardiovascular risk and VTE risk are increased mostly in the 1st year of use should be conveyed during the discussion, the different modes of availability of HRT and alternative treatments are also discussed  .The lowest effective dose for the shortest duration (2-3years), for her debilitating symptoms are discussed  and the women’s choices are respected. If the women still fears HRT, then alternative treatments (SSRI,SNRI, Gabapeptine, black  kohosh , clonidine, st.John’s  wart )are suggested.

B}The progesterogenic  side effects are due to fluid retention ,head ache, breast tenderness ,depression ,insomnia  are common and  increase in breast cancer risk has been thought to be due to progesterone component of HRT. Progestogens are added in sequential HRT ,for withdrawl bleeds .Continuous Combined HRT are being used in women with the uterus if the women wishes  mostly after 2 years of menopause. The dose of progesterone is reduced (halved) ,to decrease these side effects but requires extra monitoring , as this may give rise to irregular bleeds. Estrogen only HRT with Mirena  IUS reduces the adverse effects of estrogen only HRT,as well as the progesrogenic  side effects are reduced. The spironolactone derivatives  drosperinone and the newer progesterogens reduce the adverse effects . Redusing the dose of progesterone to just 7-10 days may lessen the  side effect. Life style modifications like exercise ,yoga, swimming, weight reduction complement the wellbeing and moodswings and thereby the effects of progesterone are reduced.Alternative treatment like SSRI (paraxetene)and SNRI (Venlafaxene),reduces the menopausal symptoms(but not like that of HRT), centrally acting clonidine and anticonvulsant(Gabapeptine)are an option to substitute the combined HRT. Phytoestrogens are yet not proved to reduce the symptoms and their adverse effects are not known.

Hrt  essay.

A)The aim of assessment is to address the  severity  of the symptoms ,interfering with her quality of life. The risks  and benefits of HRT are discussed, and her worries are explored. The women’s  vasomotor symptoms as well as other  associated symptoms  ( dyspareunia , urinary frequency, or stress incontinence due to estrogen deficiency, mood changes, depression) are assessed to give appropriate advice. Her last  menstrual period is enquired to asses her suitability for continuous  (If menopause is >2 years ,or sequential if <2 years)or sequential form of HRT. It is important to assess her risk factors for Venous thrombo embolism (VTE),a personal or first degree relative with history of VTE, should prompt a thrombophilia screen. Personal history of smoking is a risk for VTE. Personal history of Breast cancer, or a first degree relative with breast cancer is important (to advice her against HRT) , risk for ovarian cancer and endometrial cancer are assessed .A personal or a family history of cardiovascular disease is  important to advice regarding HRT,A personal or family history of osteoporosis will help to convey about the long term benefits of HRT. It is important to assess her Blood pressure and BMI as risks of HRT are more with high B.P. and morbid obesity. Investigations are usually not recommended unless there is a strong history suggestive of breast cancer or Venous thrombo -embolism . The benefits of HRT are conveyed to the women ,i.e. it helps to reduce  the debilitating  vasomotor symptoms ,benefits for mood swings, alleys depression, sexual pleasure is restored, dysparunia is reduced. On longterm use of HRT, there is reduction of osteoporosis and fractures , increases cognition , and reduces Alzimer’s disease , toothloss. The risks due to long term HRT i.e. for more than 5 years are breast cancer risk of 35/1000 and 51/1000( background risk is 32/1000 per year)if taken for 5 years and  15 years respectively is conveyed to her. The cardiovascular risk and VTE risk are increased mostly in the 1st year of use should be conveyed during the discussion, the different modes of availability of HRT and alternative treatments are also discussed  .The lowest effective dose for the shortest duration (2-3years), for her debilitating symptoms are discussed  and the women’s choices are respected. If the women still fears HRT, then alternative treatments (SSRI,SNRI, Gabapeptine, black  kohosh , clonidine, st.John’s  wart )are suggested.

B}The progesterogenic  side effects are due to fluid retention ,head ache, breast tenderness ,depression ,insomnia  are common and  increase in breast cancer risk has been thought to be due to progesterone component of HRT. Progestogens are added in sequential HRT ,for withdrawl bleeds .Continuous Combined HRT are being used in women with the uterus if the women wishes  mostly after 2 years of menopause. The dose of progesterone is reduced (halved) ,to decrease these side effects but requires extra monitoring , as this may give rise to irregular bleeds. Estrogen only HRT with Mirena  IUS reduces the adverse effects of estrogen only HRT,as well as the progesrogenic  side effects are reduced. The spironolactone derivatives  drosperinone and the newer progesterogens reduce the adverse effects . Redusing the dose of progesterone to just 7-10 days may lessen the  side effect. Life style modifications like exercise ,yoga, swimming, weight reduction complement the wellbeing and moodswings and thereby the effects of progesterone are reduced.Alternative treatment like SSRI (paraxetene)and SNRI (Venlafaxene),reduces the menopausal symptoms(but not like that of HRT), centrally acting clonidine and anticonvulsant(Gabapeptine)are an option to substitute the combined HRT. Phytoestrogens are yet not proved to reduce the symptoms and their adverse effects are not known.

Hrt  essay.

A)The aim of assessment is to address the  severity  of the symptoms ,interfering with her quality of life. The risks  and benefits of HRT are discussed, and her worries are explored. The women’s  vasomotor symptoms as well as other  associated symptoms  ( dyspareunia , urinary frequency, or stress incontinence due to estrogen deficiency, mood changes, depression) are assessed to give appropriate advice. Her last  menstrual period is enquired to asses her suitability for continuous  (If menopause is >2 years ,or sequential if <2 years)or sequential form of HRT. It is important to assess her risk factors for Venous thrombo embolism (VTE),a personal or first degree relative with history of VTE, should prompt a thrombophilia screen. Personal history of smoking is a risk for VTE. Personal history of Breast cancer, or a first degree relative with breast cancer is important (to advice her against HRT) , risk for ovarian cancer and endometrial cancer are assessed .A personal or a family history of cardiovascular disease is  important to advice regarding HRT,A personal or family history of osteoporosis will help to convey about the long term benefits of HRT. It is important to assess her Blood pressure and BMI as risks of HRT are more with high B.P. and morbid obesity. Investigations are usually not recommended unless there is a strong history suggestive of breast cancer or Venous thrombo -embolism . The benefits of HRT are conveyed to the women ,i.e. it helps to reduce  the debilitating  vasomotor symptoms ,benefits for mood swings, alleys depression, sexual pleasure is restored, dysparunia is reduced. On longterm use of HRT, there is reduction of osteoporosis and fractures , increases cognition , and reduces Alzimer’s disease , toothloss. The risks due to long term HRT i.e. for more than 5 years are breast cancer risk of 35/1000 and 51/1000( background risk is 32/1000 per year)if taken for 5 years and  15 years respectively is conveyed to her. The cardiovascular risk and VTE risk are increased mostly in the 1st year of use should be conveyed during the discussion, the different modes of availability of HRT and alternative treatments are also discussed  .The lowest effective dose for the shortest duration (2-3years), for her debilitating symptoms are discussed  and the women’s choices are respected. If the women still fears HRT, then alternative treatments (SSRI,SNRI, Gabapeptine, black  kohosh , clonidine, st.John’s  wart )are suggested.

B}The progesterogenic  side effects are due to fluid retention ,head ache, breast tenderness ,depression ,insomnia  are common and  increase in breast cancer risk has been thought to be due to progesterone component of HRT. Progestogens are added in sequential HRT ,for withdrawl bleeds .Continuous Combined HRT are being used in women with the uterus if the women wishes  mostly after 2 years of menopause. The dose of progesterone is reduced (halved) ,to decrease these side effects but requires extra monitoring , as this may give rise to irregular bleeds. Estrogen only HRT with Mirena  IUS reduces the adverse effects of estrogen only HRT,as well as the progesrogenic  side effects are reduced. The spironolactone derivatives  drosperinone and the newer progesterogens reduce the adverse effects . Redusing the dose of progesterone to just 7-10 days may lessen the  side effect. Life style modifications like exercise ,yoga, swimming, weight reduction complement the wellbeing and moodswings and thereby the effects of progesterone are reduced.Alternative treatment like SSRI (paraxetene)and SNRI (Venlafaxene),reduces the menopausal symptoms(but not like that of HRT), centrally acting clonidine and anticonvulsant(Gabapeptine)are an option to substitute the combined HRT. Phytoestrogens are yet not proved to reduce the symptoms and their adverse effects are not known.

 Hrt  essay.

A)The aim of assessment is to address the  severity  of the symptoms ,interfering with her quality of life. The risks  and benefits of HRT are discussed, and her worries are explored. The women’s  vasomotor symptoms as well as other  associated symptoms  ( dyspareunia , urinary frequency, or stress incontinence due to estrogen deficiency, mood changes, depression) are assessed to give appropriate advice. Her last  menstrual period is enquired to asses her suitability for continuous  (If menopause is >2 years ,or sequential if <2 years)or sequential form of HRT. It is important to assess her risk factors for Venous thrombo embolism (VTE),a personal or first degree relative with history of VTE, should prompt a thrombophilia screen. Personal history of smoking is a risk for VTE. Personal history of Breast cancer, or a first degree relative with breast cancer is important (to advice her against HRT) , risk for ovarian cancer and endometrial cancer are assessed .A personal or a family history of cardiovascular disease is  important to advice regarding HRT,A personal or family history of osteoporosis will help to convey about the long term benefits of HRT. It is important to assess her Blood pressure and BMI as risks of HRT are more with high B.P. and morbid obesity. Investigations are usually not recommended unless there is a strong history suggestive of breast cancer or Venous thrombo -embolism . The benefits of HRT are conveyed to the women ,i.e. it helps to reduce  the debilitating  vasomotor symptoms ,benefits for mood swings, alleys depression, sexual pleasure is restored, dysparunia is reduced. On longterm use of HRT, there is reduction of osteoporosis and fractures , increases cognition , and reduces Alzimer’s disease , toothloss. The risks due to long term HRT i.e. for more than 5 years are breast cancer risk of 35/1000 and 51/1000( background risk is 32/1000 per year)if taken for 5 years and  15 years respectively is conveyed to her. The cardiovascular risk and VTE risk are increased mostly in the 1st year of use should be conveyed during the discussion, the different modes of availability of HRT and alternative treatments are also discussed  .The lowest effective dose for the shortest duration (2-3years), for her debilitating symptoms are discussed  and the women’s choices are respected. If the women still fears HRT, then alternative treatments (SSRI,SNRI, Gabapeptine, black  kohosh , clonidine, st.John’s  wart )are suggested.

B}The progesterogenic  side effects are due to fluid retention ,head ache, breast tenderness ,depression ,insomnia  are common and  increase in breast cancer risk has been thought to be due to progesterone component of HRT. Progestogens are added in sequential HRT ,for withdrawl bleeds .Continuous Combined HRT are being used in women with the uterus if the women wishes  mostly after 2 years of menopause. The dose of progesterone is reduced (halved) ,to decrease these side effects but requires extra monitoring , as this may give rise to irregular bleeds. Estrogen only HRT with Mirena  IUS reduces the adverse effects of estrogen only HRT,as well as the progesrogenic  side effects are reduced. The spironolactone derivatives  drosperinone and the newer progesterogens reduce the adverse effects . Redusing the dose of progesterone to just 7-10 days may lessen the  side effect. Life style modifications like exercise ,yoga, swimming, weight reduction complement the wellbeing and moodswings and thereby the effects of progesterone are reduced.Alternative treatment like SSRI (paraxetene)and SNRI (Venlafaxene),reduces the menopausal symptoms(but not like that of HRT), centrally acting clonidine and anticonvulsant(Gabapeptine)are an option to substitute the combined HRT. Phytoestrogens are yet not proved to reduce the symptoms and their adverse effects are not known.

 V

a. Disscuss and justify you r clinical assessment

I would start by taking a history of when her last menstrual period was and confirm amenorrhoea for 12 months and enquire as to what menopausal symptoms she is suffering from.  I would rule out a history of abnormal bleeding which may require investigation prior to commencing HRT.  A though history is needed including previous adverse reactions to hormonal preparations such as venous thromboembolism, which would contraindicate combined HRT.  Establish whether there is a personal history of breast cancer which would be a contraindication to HRT.   I would establish if there is strong family history of breast cancer or ovarian cancer at a young age which would be a concern and relative contraindication for HRT, and may warrent a referral to a genetist to establish if BRCA gene was present.  Ask about any previous osteoporotic fractures and establish cardiovascular risk factors such as hypertension, smoking, high cholesterol which would increase the risk of stroke and VTE on HRT.  I would take a drug history including any herbal or over the counter preparations that she may have already started to try to relieve her symptoms.  I would then perform an examination by starting by measuring her height and weight to calculate the BMI, obesity increases the risk of VTE on HRT.  Measure the pulse and BP and exclude pre-existiing hypertension and listen to the heart and lungs. 

Sorry here is the rest of my answer:

b.  Progesterone is requried as this lady has a uterus and unopposed oestrogen is associated with endometrial hyperplasia and carcinoma.  Progestogenic side effects include weight gain, breast tenderness and bloating.  Progesterone can be given in different forms and women may experience a different side effect profile depending on the means of administration.  Progesterone can be given in combined HRT with oestrogen orally or transdermal (patch /gel) or progesterone can be provided via the LNG-IUS directly to the endometrium.  The transdermal patch has lower peak concentrations than the oral form and may result in less progestogenic side effects.  The LNG-IUS has the least systemic side effects as it provides the lowest dose of progesterone of all the forms available, it mainly has a local action and has the added benefit of providing contraception if the woman is peri-menopausal.  The LNG-IUS is not associated with weight gain.  Combined HRT (oral/transdermal) can involve having a monthly withdrawal bleed or can be given on a more continuous basis and have withdrawal bleeds 4 times per year.  The means of administration and the regime depends on the woman's choice and the side effects.  Different regimes may suit the woman better and be associated with less side effects.

a) I will take a detailed history regarding severity and duration of menopausal symptoms and its effect on quality of life. Ask history of hot flushes, night sweats, vaginal dryness, dyspareunia, urinary frequency or urgency or symptoms of depression. Vasomotor symptoms generally settle down in 1-3 years time. Vaginal dryness and dyspareunia may be treated with topical appication of estrogen creams. For symptoms of depression, a psychiatric assessment may be required and progesterones might further aggravate it. Ask about last menstrual period and any bleeding episodes after that. Ask history of any medical comorbidities like DM, HT, hypercholesterolemia and any DVT in past as HRT needs to be carefully selected in these patients. Ask past history of endometriosis as it may get reactivated with estrogens in HRT. History of any gynae malignany or breast cancer as estrogen and progesterone dependent malignancies may recurr with HRT.  Take history of cervical smear. Ask history of smoking as estrogen may not be advisable.  Check her weight, BP and BMI. Not much of detailed examination is required unless there is any significant history

b) Progestogenic side effects may be reduced by changing the preparation of pregesterone e.g. nor-ethisterone may be changed to medroxypreogesterone acetate. Dose of progesterone may be reduced although it should be sufficient for endometrial protection. Change the duartion of progesterones e.g instead of giving it every month, give them every 3 months. Route of administeration can be change from oral to transdermal or intrauterine.

Life - style modifications like regular excercise and low fat low carbohydrate diet is advisable

Alternative methods like evening primrose oil, vitamin E, phytoestrogens, soya-proteins, lubricants for vaginal dryness may be tried instead of giving hormones.

Tibolone may be given instead of estrogen-progesterone combination for the control of vasomotor symptoms

a)

She should be asked the severeity of her symptoms, and how it affects her quality of life. The timing of menopause should be assessed, to decided if she requires continuous or sequential regime of HRT, and the regiment should be tailored to her needs. Any personal or family history of breast cancer should be asked, as HRT  would be contraindicated. Any previous history of VTE is essential before starting, as HRT is associated with increased risk of VTE. Previous history of myocardial infarct or cerebovascular accident should also be asked, as starting HRT would place her at even a higher risk of  MI or CVA. History of smoking would increase her risk of VTE if HRT is started. Her alcohol and caffiene intake should be asked, as alcohol and caffiene is associated with bone loss during the post menopausal period. Ensure that her previous cervical smears are up to date.

Examination should include her blood pressure to screen for hypertension, and her BMI. High BMI is associated with increased risk of VTE, even without HRT. Her cardiovascular system needs to be examined, to ensure no abnormal heart sounds or cardiomegaly, and to be completed with a baseline ECG. Abdomen palpated for masses, and bimanual examinal done to assess uterine size.

Blood taken for FBC to look for baseline hemoglobin, U&E and LFT to look as baseline renal and liver functions respectively. A baseline fasting serum lipid to look for hypercholesterolemia. Baseline mammogram to screen for breast masses before starting HRT. A baseline DEXA scan to look at bone density.

Written information leaflets should e provided, and she may need referral to a postmenopausal support group.

b)

Progesterone is associated with distressing side effects, among others, mood swings, PMS- like symptoms, water retention and acne. To reduce the progestorone side effects, the progestogen pill can be reduced to 7 -10 days, instead of the usual 14 days duration. Alternatively, the use of  newer generation progestogens, such as progestin or Drosperinone can reduce the unwanted side effects. Drosperinone is a 17-hydroxy progestogen with a spironolactone- like side effect that reduces water retention. Transdermal patches avoid the systemic effects of progesterone via controlled hormone release through a semi permeable membrane. Use of LNG-IUS can also reduce the systemic effects of progesterone by acting directly on the endometrium.

Alternatively, other non hormonal drugs, such as Tibolone, Clonidine, SSRIs and Duloxetine can be used instead. These drugs act to reduce the clilmectric symptoms, at the same time, reduces the risks of breast cancer, MI and VTE, compared to the hormonal preperaations.

Natural remedies like Black Cohosh, or Isoflavones are also alternatives to consider, as they may not cause distressing side effects as their hormonal counterparts.

I will ask  about history  of hot flashes . night sweating , mood changes  dyspareunia  and vaginal  dryness  and how much these symptoms affect her  quality of life?  . Whether she is smoking or hypertensive as  these increase risk of coronary  artery disease.  HRT is not recommended  in  women with established  coronary artery  disease and if she developed  coronary disease  while taking HRT she must stop it  .Previous or current or family history  of DVT  because  HRT is  not recommended in  women with DVT, it increase risk 2-3 fold .Previous or family history of breast cancer as HRT contraindicating in women with cancer breast  it increase mortality of breast cancer and stimulate cancer growth. HRT can be used in women with previous history  of breast cancer  if there  is no evidence of recurrence in previous  5 years after review of oncologist .History of inflammatory bowel disease , sickle cell disease or  myeloprolifertative  disease  HRT is  not recommended  in these conditions If is welling to have regular cycle she can use sequential HRT .Family history of osteoporosis as  HRT is reduced incidence of  vertebral fracture .Check her  blood pressure  and BMI as  obesity is additional risk factor for thromboemolism. Pelvic  examination to detect genital atrophy because she will benefit from local estrogen application..                                            

B  . To minimize side effect of progestogen reduce the dose , change type of progestogen can use             transdermal patch or MRINA. Use progestrogens for   long cycles 14 days every 3 months or use combine continous HRT. Life style modification avoid use of caffeine and exercise  will improve her symptoms .Use of alternatives to HRT as clonidine  for vasomotor symptoms ,SSRI or complementary therapy as red colver, derivative of soy and black cohosh. Provide her with written information.                                                       

A 52 year old woman (uterus in-situ) has been referred to the gynaecology clinic because of debilitating menopausal symptoms and worries about taking hormone replacement therapy.

(a) Discuss and justify your clinical assessment [11 marks]

I will ask about the menstrual history regarding her LMP and regularity as a continuous regimen is more suitable with postmenopausal ladies while a sequential regimen is more suitable with perimenopausal ladies. I will ask about the severity of her symptoms and effect on quality of life to be able to assess the effect of treatment. i will ask about specific symptoms as HRT is suitable with vasomotor symptoms while symptoms as vaginal dryness will be better managed by topical agents while symptoms of incontinence or prolapse don't improve with HRT. I will ask about general life style factors as exercise since regular aerobic sustained exercise improve vasomotor symptoms while irregular high impact exercise actually worsen vasomotor symptoms. smoking and alcohol intake worsen symptoms. I will ask about previous use of complimentary therapy ( phytoestrogens,black cohosh,primerose oil,ginseng,st johns warts,acupuncture or homeotherapy) and their effect on her symptoms and also to assess drug interactions .i will ask about history of cardiac disease as hypertension and ISHD as HRT is associated with increased risk of coronary artery events in the first year of use in women without previous coronary artery disease and for women with pre existing coronary artery disease HRT is better avoided as recommended by the newyork heart association. i will ask about risk factors for endometrial carcinoma as history of PCOS, diabetes, early menarche or family history of endometrial cancer as sequential HRT is associated with increased risk of endometrial cancer while continuous HRT is more protective. I will ask about family history of cancer ovary or known presence of BRCA mutation as HRT is associated with increased risk of ovarian cancer. i will ask about history of breast cancer as HRT is associated with increased risk of breast cancer and in prescence of treated cancer breast without recurrence she will need referral to oncologist and specialist menopausal clinic to assess suitability for HRT. I will ask about history of VTE and thrombophilia as oral HRT is better avoided in presence of history of VTE even in absence of thrombophilia while HRT is better avoided with high risk thrombophilias as factor v leiden mutations and alternative treatment would be recommended. Examination will include a BMI as obesity is risk factor for VTE,endometrial cancer and CVS disease. blood pressure and cardiac examination to assess cardiovascular status. abdominal examination for palpable massess. pelvic examination is not necessary unless symptoms of prolapse or incontinence.

(b) Discuss the steps that can be taken to minimize progestogenic side-effects associated with combined hormone replacement therapy [9 marks].

Progestogenic side effects can be reduced by using the lowest effective dose of progesterone.this can be helped by advice about life style changes as exercise,smoking and alcohol intake which help reduce symptoms and hence help with reducing the doses. Using mirena IUS as the progesterone component of HRT reduces systemic side effects and is licensed for 4 years. changing the type of progesterone may be effective with some symptoms as drosperinone which reduces androgenic side effects and reduces water retention and is not accompanied by weight gain. using continous combined regimens is associated with reduced duration and hence side effects of progesterone also using longer cycle regimens (progesterone for 14 days per cycle) helps reducing side effects. Transdermal progesterone is not effective in controlling symptoms so not recommended. finally,if side effects could not be tolerated alternatives to HRT as clonidine,gabapentine,SSRI,SNRI and topical moisturisers should be discussed.

1)I ll ask for age of menopause as if less than one year I ll offer sequential regimen of HRT and if more than one year I ll offer combined regimen of HRT.I ll ask for details of symptoms like what type of symptoms she is having,duration and severity of symptoms as I ll tailor HRT regimen according to her individual needs.I ll ask for personal or family history of VTE as HRT may be contraindicated in case of VTE.I ll ask for history of any known thrombophilia.Thrombophilia screening is not recommended routinely but may be indicated if there is history of thrombophilia in some family member.I ll ask for personal or family history of breast cancer as HRT with breast cancer is having conflicting data according to WHI study so need more caution.I ll ask for history of ovarian cancer and endometrial cancer as HRT may be contraindicated in some type of cancer like granulosa cell tumours of ovary and sarcoma of uterus.I ll ask for history of stroke or MI as combined regimen increases the risk of coronary heart disease according to WHI study.I llask for life style habits like alcohol or smoking as avoidance of these may be benificial for relief of some symptoms.I ll ask for diet and exercise as food rich in calcium and weight bearing exercise ll decrease risk of osteoporosis.I ll ask for use of over the counter drugs like soy,black cohosh as it may have interactions with HRT regimen.I ll check baseline BP and BMI as obesity is a risk factor for VTE.I ll do abdominal examination to look for palpable masses.I ll do pelvic examination only if needed like in case of abdominal mass.                                                        2)I can reduce dose of progestogen to half.I canreduce duration of progestogen in sequential regimen like for 7 to 10 days.Reducing dose or duration may result in withdrawl bleed so there should be low threshold for ultrasound and endometrial biopsy.I can change type of progesten like progesterone and dydrogesterone have low side effects due to receptor specificity.I can change route of progestogen administration as transdermal preparation or vaginal ring or passery or gel may have less side effects.I can advice LNG INS as progetogen arm of HRT regimen.It is licensed in UK for 4yrs for this use.I can advice alternative like tibolone instead of conventional HRT regimen with estrogen and progeston combination.

I forget to write about drospirenone.It is spironolectone derivative with antiendrogenic and antimineralocorticoid properties and have less side effect profile

A)Menstrual history is taken about her LMP.If it is less than a year, she would be given sequencial HRT with progesterone for 10-12 days. In case her LMP is more than a year ago,she can take take combined continuous HRT for a period free treatment. She should  be enquired  about impact on  QOL, and the most bothersome symptom, so that the treatment may be tailored to her specific  need. Previous contraception history and any complications with particular contraceptive ,should be asked.

Personal or family history of any risk factors for cardiac disease,such as hypertension ,  ischemic heart disease should be taken , as HRT increases risk of cardiovascular disease.

Past or family history of  VTE  or thrombophilia is taken as HRT is associated with increased risk of VTE. Any personal or family h/o breast cancer, endometrial  cancer as risk is further increased with HRT. Personal history of smoking is taken as it increases the risk of cardiac disease and VTE ,while on HRT. Family history of osteoporosis is taken,as this  will   increase her risk of osteoporosis . HRT would prevent both spine and hip osteoporosis related fractures.

Drud history ,both prescribed andover the counter,should be taken ,so that any interaction can be assessed.

On examination BMI is noted.Obesity is risk factor for cardiac disease and VTE,which will further increase by using HRT.BP is noted as base line.Abdominal examination is done and any abdominopelvic  masses noted.

Thrombophilia screening is not routinely done,unless there is family h/o of thrombophilia.

B)Woman would need progesterone with HRT to reduce her risk of endometrial cancer.Side effects of progesterones include headeache, breast tenderness, weight gain .Androgenic side effects i.e acne or hirsutism. Mood swings or PMS like side effects. These would limit her compliance. Attempts can be taken to reduce these side effects.Dose of progestogens can be halved or duration reduced to 10-12 days. This may result in bleeding and hyperplasia.USS and endometrial sampling  should be done if needed.

HRT with Progesterone and dydrogesterone have fewer side effects due to receptor specifity.Progesterone is available in oral micronized form ,vaginal  pessaries and gel.These formulations of progesterone reduce the metabolic impact and risk of VTE.

Levonorgestrel intrauterine system,can be used to minimize the systemic side effects.It is licensed  for 4yrs in UK for progestogenic opposition .

Drosperinone which is spironolactone analogue, has antiandrogenic  and animineralocorticoid properties.It is incorporated  with low dose estrogen in continuous combined pills ,which will reduce androgenic side effects and water retention.

Tibolone is another option  instead of oertogen progestogenic  HRT .