Hormone Replacement Therapy (HRT)


Medication with oestrogens or a combination of oestrogens and progestogens (including perimenopausal use of oral contraceptives) for the treatment of climacteric symptoms or for the prevention of osteoporosis and cardiovascular diseases is hormone replacement therapy HRT.


 

IS THERE ANY NEED TO HRT?

  1. Initially menopause was considered as a process of normal ageing and though women had symptoms they were not treated but either left along or given some symptomatic treatment.

  2. In current times not only women have become health conscious, but today they have greater aspirations and are pursuing high profile career in all the fields and want to continue doing that even in postmenopausal life.  Women today have greater expectations of a higher quality life than their mothers and grand mothers and therefore, will pose challenge about their health care in their 7th and 8th decades.

  3. Now the endocrine & metabolic changes occurring with menopause are well known.  Postmenopausal hormone therapy should be viewed as specific treatment for symptoms in the short-term and preventive pharmacology in the long term.

WHAT IS MENOPAUSE ?

  • It is characterized by an exclusive marker event-the ceasing of menstruation.

  • It's a natural progression of your life and is not a disease.

  • It is the end of reproductive life and not the active productive life.

  • Menopause or the "change of life" affects each woman in a different way.

WHY DO THE PERIODS STOP ?

Each month a women's body is prepared for pregnancy by two natural hormones, oestrogen and progesterone.  Oestrogen builds up the uterus lining.  Progesterone completes the preparation of the uterus.  If the women does not become pregnant the level of the two hormones drop and you have a period.  As a woman gets older, her ovaries make less and less oestrogen-the whole monthly cycle is already and in time comes to a halt.

 

 

WHAT ARE THE SIGNS ?

Common changes you might notice are:

  • Irregular periods

  • Hot flushes

  • Vaginal dryness, urinary problems

  • Discomfort during sexual intercourse

  • Lack of libido

  • Mood Changes especially depression

  • Thinning and dryness of skin

  • Other problems like memory lapses, headaches, irritability.

INDICATIONS FOR SYMPTOMATIC TREATMENT.

  STRONG INDICATIONS

  • Hot flushes and sweating

  • Urogenital atrophy

  • Genital attrophy

  •  Incontinence

  • Recurrent urinary tract infection

  • Perimenopausal cycle disorders

POSSIBLE INDICATIONS

  • Atypical complaints and lack of well being

  • Depressive mood changes

  • Joint and muscle complaints

  • Epithelial atrophy

INDICATIONS FOR PREVENTIVE TREATMENT

  • Osteoporosis

  • Cardiovascular Disease.

WHO NEEDS HRT ?

HRT should be considered seriously in:

  1. Adolescents with ovarian dysfunction and severe oligo-amenorrhoea (e.g. Turner, anorexia nervosa, athletes).

  2. Women with premature menopause.

  3. Women with a bone mass value more than 1 SD below the age-adjusted mean.

  4. Women with a history of osteoporotic fractures.

PRINCIPLES IN THE MANAGEMENT OF MENOPAUSE

  1. As with any form of drug therapy, oestrogens should be used only for responsible indications, in the smallest effective dose, and for the shortest period that satisfies therapeutic need.

  2. When oestrogen is given to menopausal women with intact uteri, cyclic administration is recommended to avoid continuous stimulation of the endometrium.
    The incidence of endometrial hyprplasis is :

    • 20% when progestogens are withheld

    • 5% when progestogens are administered for 7 days

    • 0% when progestogens are administered for 10 days or more

     

  3. Any vaginal bleeding in the postmenopausal patient must be investigated.

  4. At least yearly monitoring of asymptomatic patients treated with oestrogens should be performed and may include histologic or cytologic sampling , pelvic and breast examinations and measurements of blood pressure should also be done.

  5. Patient should be fully informed of the relative risks and benefits before treatment is initiated.

PRE-TREATMENT ASSESSMENT

HISTORY

  • Symptoms associated with climacteric.

  • Past/present medical history.

  • Past/present history of psychological disturbances.

EXAMINATION

  • Assessment of cardiovascular and respiratory systems.

  • Breast/abdominal/pelvic examinations

  • Cervical smear to screen for cervical pathology.

  • Lateral vaginal smear for determining maturation index.

INVESTIGATION

1. MAMMOGRAPHY - recommended in women over 50 and in younger high-risk patients with a family history of breast cancer or a past history of breast disease such as labular or ductal hyperplasia or epitheliosis with atypia.

 

2. USG/TVS

  • For assessment of ovarian size and volume to screen for ovarian cancer.

  • Color Doppler to assess ovarian blood flow (to screen for Ca ovary).

  • To rule out uterine and endometrial pathology.

A postmenopausal endometrial thickness > 5 mm is strongly associated with a polyp or adenocarcinoma.

 

3. ENDOMETRIAL BIOPSY/HYSTEROSCOPY

Indicated only for irregular perimenopausal or postmenopausal uterine bleeding.

 

4. HORMONE PROFILE

Indicated in suspected cases of premature ovarian failure.  At least two sets of FSH and LH values are required to refute/support this diagnosis.

 

5. LIPID PROFILE

Offer baseline levels for further assessment.

 

6. COAGULATION TEST

Reserved for women with previous deep vein thrombosis or pulmonary embolism, since an association of such thrombotic episodes with early pregnancy or combined contraceptive pill use, increases the risk of HRT

 

7. LIVER FUNCTION TESTS

Indicated if there has been a recent history of liver disease.

 

HORMONE THERAPY

1.  OESTROGEN ONLY

  • Used in postmenopausal women who have undergone hysterectomy as the need for endometrial protection does not exist.

  • In case of severe progesterone intolerance-with careful monitoring and an annual screening endometrial biopsy.

1.1  EFFECTS OF OESTROGENS

  • Weight gain

  • breast tenderness

  • nausea

These usually resolve within six to eight weeks.  If the symptoms persist for more than three months, estrogen over dosage is suspected and dosage reduced.

 

1.2  ADVANTAGES OF NON ORAL ROUTE

  • Low dose pure oestradiol

  • Avoids intestine and liver metabolism

  • Physiological oestradiol/oestrone ratio

  • Less side effects

  • Reduces serum triglyceride

1.3  CONTRAINDICATION TO OESTROGEN REPLACEMENT THERAPY

a.)  ABSOLUTE CONTRAINDICATIONS

  • Undiagnosed vaginal bleeding.

  • Acute liver disease

  • Chronic impaired liver function

  • Acute vascular thrombosis

  • Neuro ophthalamologic vascular disease

  • A past history of tumors of the breast, uterus or CSN including melanomas.

b.)  RELATIVE CONTRAINDICATIONS

  • Preexisting hypertension

  • Fibrocystic disease of breast

  • Uterine leiomyoma

  • Familial hyperlipidemia

  • Migrainous headaches

  • Chronic Thrombophlebitis

  • Endometriosis

  • Gall Bladder disease.

2.  CYCLIC OESTROGEN-PROGESTERONE HRT

  • Disadvantage of cyclic progestogen supplementation is that vaginal bleeding occurs in 50% of women.

  • Besides the side effects of progestogens include symptoms similar to premenstrual syndrome and this leads to noncompliance.

2.1  Side effects of progestogens include

  • Breast tenderness

  • Bloated ness

  • Nausea

  • Oedema

  • Abdominal cramps

  • Psychological complaints :
    1.) Depression
    2.) Anxiety
    3.) Irritability

  • C-19 Nortestosterone derivatives cause more androgenic side effects C-21 derivatives cause psychological problems 12

  • It includes perimenopausal contraception.

3.  CONTINUOUS OESTORGEN-PROGESTERONE HRT

Since withdrawal bleeding is unacceptable to most patients combined continuous regimes may improve compliance.

 

4.  HRT USING ONLY PROGESTOGEN

a.)  Used in perimenopausal HRT :

  • When cycle disturbances predominate

  • In benign breast disease.

  • When estrogens are contraindicated.

b.)  High doses of progestogens act on the hypothalamus to lower serum gonadotropins and on the thermoregulatory centre controlling vasomotor symptoms.

 

5.  COMBINED PREPARATIONS AVAILABLE FOR HRT

  • Combined preparation is given for 3 weeks in every month.

  • A biopsy should be performed on all recipicents of oestrogen-progesterone therapy after two years of treatment even in the absence of unscheduled bleeding.  The presence of endometrial hyperplasia dictates discontinuation of oestrogen-progestin therapy or more prolonged use of progestin.

6.  MIXED OESTROGEN AND ANDROGEN PREPARATION

   Given mainly for symptoms related to decreased libido available as :

  • Conjugated oestrogen + oral methyltestosterone 1.25-5 mg

  • or l75 mg testosterone pallet

  • or I/M injection of testosterone (depo and ester formulation)

DURATION OF THERAPY

  • It should be individualized to each woman's needs and perceptions and also to a clinical balance of risk and benefit.

  • It's recommended that HRT be taken for at least 5-7 years beyond the average age of menopause to confer appreciable protection against osteoporosis.

ALTERNATIVES TO HRT

1.)  DIET

  • A daily calcium intake of 1000 mg is necessary to reduce bone loss during menopause.

  • Balanced diet with fruits, vegetables, semi-skimmed milk, and adequate vitamins (folic acid, Vit. B6, C&E) and minerals (Calcium, Zinc and Copper) are recommended.

  • Reduction or avoidance of smoking and alcohol consumption is advisable.

1.1   ROLE OF DIET :      

  • Pantothenic Acid and PABA have been shown to help relieve the nervous irritability during the menopause.

  • Vit. B6 and Magnesium complement each other to reduce anxiety and depression during the menopause.  Moreover, Vit. B12, thiamine, Niacin and folate are absolutely essential for healthy nervous system because the brain has special need for them to perform at its best and is more sensitive to fluctuations in the body levels of these nutrients.

  • A number of minerals, mainly chromium, Magnesium and Zinc, alongwith the Vitamins C, B6 and Niacin help to control the balance of glucose in the body.  An imbalance of glucose can be associated with mood swings as are commonly experienced throughout the day, often resulting in difficulty getting to sleep.

  •  A deficiency of Biotin has been associated with lack of energy, sleeplessness and a disturbed nervous system.

2.)  EXERCISE

  • Walking or swimming for 20-30 minutes/day are effective in improving circulation.

  • Weight bearing exercise is particularly beneficial.

2.1    WHY SHOULD I BOTHER ABOUT EXERCISE ?

   Some of the benefits of regular exercise:

  • It helps you lose weight and stay active

  • It helps strengthen you muscles and bones (prevents brittle bones)

  • It helps you relax and reduces stress

  • It relieves depression.

   But there are also lots of other bonus benefits :

  • It keeps you mobile and supple (most important as you get older).

  • It helps your heart and lungs (and most other parts of your body) work better.

  • It can also be a good way of meeting people and making friends.

WHAT CAN I DO ABOUT THE MENOPAUSE ?

Some women have no trouble with the menopause, so don't assume it is going to be awful.  What you can do to help yourself:

  • Eat a healthy balanced diet

  • Exercise and maintain in ideal weight

  • Wear cotton clothes and undergarments

  • Avoid hot, stressful situations

  • See your gynaecologists for routine cancer screening programmes mammogram, pap smear, pelvic examination and breast examination

  • Consider hormonal and non hormonal therapies for symptom relief and long-term benefits.

ADVANTAGES OF HRT

  • Reduces hot flushes and sweats

  • Prevents vaginal dryness

  • Reduces the risk of osteoporosis (Brittle bones)

  • Protects from cardiovascular disease

  • Improves memory performance

  • Reverses changes at the bladder outlet.

HOW LONG SHOULD HRT BE TAKEN ?

A course of treatment can last from six months to several years.  Women who have had their ovaries removed before the menopause often taken it for much longer.  Taking HRT/ERT for more than 5 years will also help delay osteoporosis and may protect against heart disease.  It should improve your cholesterol level and may also help your memory.

 

 

POTENTIAL RISK ASSOCIATED WITH HRT

  UTERINE CANCER

  • Risk increase with increase duration of HRT use of 3 to 6 fold increase after 3 to 10 years.  10 fold increase after 10 years, 22

  • Oestrone use the greater risk than oestradiol and oestriol.

  • Risk is higher with higher dose of HRT

  • Risk is reduced by adding progestogen.

  BREAST CANCER

When oestrogen therapy is used for more than 10 years, risk of breast cancer increase by 1.3 to 1.8 fold.

  • HRT should not be given to a high risk group for breast cancer.

  • In patients with family h/o carcinoma breast, investigations should be done for BRCAI & II gene and if present should be regularly monitored by 6 monthly mammography & breast self examination after starting HRT.

  • In patients of CA breast. Tamoxifen may be used.  Agonistic oestrogenic actions of tamoxifen on bone and lipids with offer protection against osteoporosis and cardiovascular disease while its antagonism of oestrogen at breast will prevent recurrence and contralateral disease.

  OVARIAN CANCER

Currently it has been shown that there's no increase of ovarian cancer with HRT.