All types of traditional HRT contain an oestrogen hormone. It is the replacement of this hormone that is key to most of the benefits of hormone replacement. However, the ovaries also produce other hormones, such as progesterone, which must be replaced with the oestrogen if you still have your uterus.
This is very important because taking oestrogen alone causes the lining of the womb (uterus) to become thicker. This overgrowth (hyperplasia) can lead to unusual bleeding patterns and in some circumstances the thickened lining can become abnormal and increase the risk of cancer of the uterus (endometrial cancer). This risk is counteracted by taking progesterone with the oestrogen, in a similar way to the oestrogen and progesterone found in the combined contraceptive pill.
HRT is available as tablets, patches, gels and vaginal rings. It delivers a set amount of oestrogen into your bloodstream each day but some forms, like tablets, cause the levels in the blood to go up and down and others ensure the levels are constant at all times of the day. This is important as it can influence the side effects you experience and for can influence some of the risks of taking HRT. The type of preparation you choose will depend on your preference and any risk factors you may have.
It is also possible to use HRT that only works locally on the vaginal and vulva (local HRT). This is useful if you don’t want to take hormone replacement that is absorbed into your body (systemic HRT), or if you have been advised not to take systemic HRT or if you still have local symptoms despite taking systemic HRT. You can use pessaries, creams or vaginal rings to replace oestrogen locally.
Non-Hormonal Approaches
Most women upon experiencing the early symptoms of the menopause will seek out a solution from the wide range of alternative and ‘natural’ solutions available in reputable pharmacies, supermarkets, health food shops, high street herbalists, clinics and on-line suppliers with various levels of reliability.
Usually a woman will present for medical input after she has tried or discounted some of the above measures. She should be informed of the beneficial effects of lifestyle measures before exploring appropriate non-hormonal measures.
Alternative and Complementary Treatments
This group of treatments are widely available (Table 5) but very poorly researched in the scientific manner that the medical profession requires to make evidenced based clinical decisions. This can make it difficult to fully counsel a woman as to how effective the treatment is, how long any effect will last and, most importantly, how safe the therapy is. Efficacy is usually limited and of a short duration with the potential for interactions with other pharmaceutical agents.
| Therapy | Treatment |
|---|---|
| Complementary drug free therapies (Delivered by a practitioner) | Acupuncture
Reflexology Magnetism Reiki Hypnotism |
| Herbal/Natural preparations (Designed to be ingested) | Black cohosh (Actaea racemosa)
Dong quai (Angelica sinensis) Evening primrose oil (Oenothera biennis) Gingko (Gingko biloba) Ginseng (Panax ginseng) Kava kava (Piper methysticum) St John’s wort (Hypericum perforatum) |
| ‘Natural’ hormones (Designed to be ingested or applied to the skin) | Phytoestrogens such as isoflavones and red clover
Natural progesterone gel Dehydroepiandrosterone (DHEA) |
When counselling a woman taking a ‘natural’ hormone it is important to make her aware that these are essentially weak HRT and that if they are taking a high dose therapy there is a possibility they could be exposing themselves to the known risks of HRT.
Non-Hormonal Prescribable Treatments
This group of therapies (Table 6) is increasingly important to consider in the management of women who do not wish to or are unable to take hormones for various reasons which may include previous diagnoses of hormone sensitive cancers such as breast cancer.
| Treatment of Vasomotor Symtpoms | |
|---|---|
| Alpha-adrenergic agonists | Clonidine |
| Beta-blockers | Propanolol |
| Modulators of central neurotransmission | Venlafaxine
Fluoxetine Paroxetine Citalopram Gabapentin |
Table 6. Non-Hormonal treatments for vasomotor symptoms
Other issues specific to the menopause can also be treated without hormones using prescribable preparations. These include vaginal moisturisers for vaginal dryness and some of the many ways of treating osteoporosis which include bisphosphonates, raloxifene and teriparatide.
Hormonal therapy
Hormone replacement therapy (HRT) has been the mainstay of the treatment of menopausal symptoms for decades. Its use has always attracted controversy, initially in its promotion as a drug with rejuvenating abilities, and then a confusing period where long term benefits on osteoporosis and cardiovascular disease prevention from large cohort studies were unclear. In 2002 a large randomised trial highlighted a series of potential risks from HRT use that attracted so much media attention that many women either stopped treatment themselves or their prescribers stopped.
Since the initial publication of this study there have been significant changes in the data presented from the study. These new data along with subsequent studies have either significantly reduced or removed the risks initially described. It is important when digesting risks of hormone therapy that recent publications (preferably after 2010) are considered.
Types of hormones
Estrogens
This is a group of hormones with estrogenic activity. They include
- Estradiol (the main physiological Estrogen)
- Estrone Sulphate
- Estriol
- Congugated equine Estrogens
Systemic estrogen only HRT is suitable just for women who no longer have a uterus following a hysterectomy. If estrogen is given without progestogenic opposition there is a risk that in time endometrial hyperplasia and cancer may develop.
Estrogen with Progestogen
The administration of progestogen is necessary to protect the endometrium in women who have not had a hysterectomy. It is normally given cyclically in preparations over a 28 day cycle of which 16-18 will estrogen alone and 10-12 days will be with estrogen and progesterone combined (cyclical HRT). This results in regular monthly menstruation and is suitable for women during the perimenopause or early postmenopausal years.
Estrogen and progesterone may be given continuously (continuous combined HRT) to women who are known to be postmenopausal or over the age of 54 years. These are usually preparations with the same dose of daily estrogen combined with a smaller dose of progestogen taken every day. These regimes normally result in about 90% of women not experiencing vaginal bleeding.
Several types of progestogens are used in HRT by different manufacturers including:
- Norethisterone
- Levonorgestrel
- Dydrogesterone
- Medroxyprogesterone acetate
- Drospirenone
- Micronised progesterone
A change of type, dose or route of progestogen is occasionally required to reduce unwanted effects of the drug.
Testosterone
Testosterone has traditionally been given to women with disorders of sexual desire and energy levels who have failed to respond to normal HRT. These beneficial effects of testosterone are well documented however few long term studies into the adverse effects of testosterone exist.
Over the past years manufacturers have stopped making testosterone drugs for women to the point that the only available preparations available now are those licensed for use in men. This usually means that testosterone needs to be instigated under the care of a doctor with specialist menopause knowledge.
Routes of Hormone Therapy Administration
The two main routes of HRT delivery are oral and transdermal. The oral route is normally a daily tablet that contains the appropriate mix of estrogen and progestogen, depending on the preparation. The oral route is convenient and cheap but does influence lipid metabolism and the coagulation system through its effects on the liver during first pass metabolism.
The transdermal route, either given as patches applied to the skin on the trunk or as measured amounts of gel, is also effective, with the advantage of delivery of estradiol directly into the circulation, avoiding the above potentially adverse effects on the liver and the coagulation system.
Estradiol is also available as measured dose creams or small pessaries that are an important factor in the management of lower genital tract symptoms.
Progestogen in the form of Levonorgestrel may be administered as an intrauterine releasing system (IUS), Mirena®. This device not only provides contraception and control of troublesome bleeding but also provides endometrial protection for up to 4 years.
Beneficial Effects of Hormone Therapy
Key benefits of HRT
Symptoms improved
- Vasomotor symptoms
- Sleep Patterns
- Performance during the day
Prevention of osteoporosis
- Increased bone mineral density
- Reduced incidence of fragility fractures
Lower genital tract
- Dryness
- Soreness
- Dyspareunia
Cardiovascular disease
- Preventative effect if started early in menopause
Vasomotor symptoms
The principal reason for taking HRT is vasomotor symptom improvement. Well over 90% of women note a significant improvement within 6 weeks, with reductions in frequency and severity of hot flushes and night sweats with consequent improvements in sleep and daytime energy levels as well as concentration.
The Skeleton
The protective effects of HRT on the skeleton include prevention of bone loss and the prevention of osteoporotic fractures of the hip and spine. The use of HRT is strongly recommended for women after premature ovarian failure as they are at a much greater risk of osteoporosis. Most postmenopausal women should consider HRT as a means to prevent bone loss, especially if they require HRT for other symptomatology.
The Lower Genital Tract
Both systemic and locally administered HRT have significant beneficial effects on the lower genital tract. There is good evidence that its administration improves vulvovaginal dryness, irritation, soreness and dyspareunia. There is also an improvement in symptoms of cystitis and occasionally dysuria. Local hormone therapy is unlikely to cure prolapse but may improve some of the symptoms of prolapse. There is no evidence that local HRT improves incontinence. Many women considering local HRT are dissuaded from its use due to concerns about the published risks of Hormone therapy. They can often be reassured that were they to use the most potent form of local hormone therapy as a 10ųg twice weekly dose they would only be administering approximately the equivalent of a 1mg oral tablet over a whole year.
The Cardiovascular system
The cardiovascular benefits of HRT were first demonstrated in large observational cohort studies. The principal benefits were reduction in ischaemic heart disease and overall mortality. However the large randomized Women’s Health Initiative (WHI) study demonstrated reductions in survival from cardiovascular disease in women taking HRT. This study has been widely criticised due to the overweight and generally older population studied; a population probably at greater risk of CVD. The current understanding is that there is a ‘window of opportunity’ in the perimenopausal or early postmenopausal years during which the administration of HRT may reduce the morbidity and mortality from CVD by prevention of atheroma formation.
Whilst the prevention of CVD is not currently a licensed indication for HRT the data are sufficient to include a discussion with women that they should consider these benefits.
The Colon
Whilst the WHI study demonstrated a clear benefit of HRT on the incidence and mortality of colon cancer the use of HRT to prevent this malignancy is not indicated.
Prescribing and Side Effects of Hormone Therapy
Prior to prescribing HRT it is important to weigh up the indications, proposed benefits and potential risks for each individual patient individually. For example hormone therapy may be contraindicated in a patient with a prior history of breast cancer or thromboembolic disease.
Absolute Contraindications
- Suspected pregnancy
- Breast cancer
- Endometrial cancer
- Active liver disease
- Uncontrolled hypertension
- Known VTE
- Known thrombophilia (e.g. Factor V leiden)
- Otosclerosis
Relative Contraindications
- Uninvestigated abnormal bleeding
- Large uterine fibroids
- Past history of benign breast disease
- Unconfirmed personal history or a strong family history of VTE
- Chronic stable liver disease
- Migraine with aura
In general side effects with HRT are few and minor. It is important before starting HRT to ensure that the woman has no contraindications to HRT and to ensure that she has had no serious effects in the past when on the contraceptive pill such as venous thrombosis or migraine with aura.
Side effects associated with estrogen:
- breast tenderness or swelling
- nausea
- leg cramps
- headaches
Side effects associated with progestogen:
- fluid retention
- breast tenderness
- headaches
- mood swings
- depression
- acne
Most side effects can be managed with a change in dose of estrogen or a change in type of progestogen. Some patients can also benefit from a switch of route. Many women find the IUS a useful device as it delivers much less progestogen into the circulation, thus reducing progestogenic side effects.
The duration for which a woman should take HRT is frequently debated. There is little clear evidence to support how long but it is recommended that there should be no exact maximum age at which a woman should stop HRT, rather employing regular assessment of the woman and her needs along with review of the type and dose of HRT she is taking.
Risks of Hormone Therapy
The risks attributed to HRT have attracted much media attention. At present, due to a combination of reanalysis of the data, new studies and a better understanding of the communication of risk many more women are considering HRT in the management of their menopause.
Cancer
Breast cancer is without doubt the cancer that attracts most concern from patients and most attention from the world’s media. The studies performed still do not fully inform patients of the additional risks they expose themselves to by using HRT. Useful figures to quote are that the background risk of Breast cancer in this age group is in the region of 50 per 1000 women for 10 years and with 5 years HRT use there are an additional 2 – 6 cancers with combined HRT, which reverts to the background risk 5 years after stopping HRT. It is important to be aware that recent data with estradiol HRT suggests that mortality from breast cancer is not increased.
Endometrial cancer and ovarian cancer are not considered significant risks with HRT use. Endometrial malignancy risk is largely eliminated if women are given progestogens. Ovarian cancer has not been shown to significantly increase in incidence with HRT use.
Cardiovascular Disease and Stroke
As discussed above most of the effects of HRT on the cardiovascular system when given to younger women are beneficial. However when given to older women the effects may become deleterious. The degree to which this happens is unclear but is likely to be higher in women taking combined HRT.
Stroke incidence has a similar age effect, with the increased incidence greater in the older woman. The effect is small, and is only on the incidence of ischaemic stroke, thought to be an increase of and additional 2 women per 10,000 women per year when on HRT.
Venous Thromboembolism (VTE)
The influence of HRT on the clotting system is similar to that of the oral contraceptive. The background incidence of all VTE in women over 50 is low (approximately 15-20per 10,000) and HRT doubles this risk. There is evidence to suggest that transdermal HRT through its avoidance of effects on the liver may not have such a great effect on VTE incidence.