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HRT in practice: helping women make the right choice

Lilian M Azzopardi
Senior Lecturer

Anthony Serracino Inglott
Professor and Head of Department

Maurice Zarb Adami

Senior Lecturer

Fiona Galea
Pharmacist
Department of Pharmacy
Faculty of Medicine & Surgery
University of Malta  

The use of hormone replacement therapy (HRT) has been at the centre of discussions since its initial clinical use in the 1970s. With the recent studies reporting the risk of breast cancer associated with the use of HRT, guidelines on the management of menopausal symptoms have been amended.
During the last century a gradual increase in life expectancy was witnessed, but the age of menopause has not changed. Therefore many women now spend from a third to a half of their lives in postmenopause.

The menopause
The menopause is the state that is defined as the permanent cessation of menstruation due to loss of ovarian follicular activity and a decline in oestrogen levels. Cessation of menstruation followed by a 12-month menstruation-free period usually defines the onset of the menopausal state. During the perimenopausal phase, however, many women report erratic periods.
There are some factors that influence the age of onset of menopause: for example, thinner women are prone to earlier menopause because of lower body fat, which contributes to oestrogen production (see Table 1).(1)

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Menopausal symptoms
During the perimenopausal phase and during menopause, women may experience multiple symptoms due to hormonal deprivation.

Vasomotor symptoms
Vasomotor symptoms present with a sudden onset of reddening of the skin over the head, neck and chest, accompanied by a feeling of intense body heat and occasionally profuse perspiration. The duration varies from a few seconds to several minutes and rarely for more than an hour. These symptoms are more frequent and severe at night or during times of stress. The hot flushes coincide with a surge in luteinising hormones.

Respiratory symptoms
The increased prevalence of snoring and obstructive sleep apnoea syndrome is attributed to decreased endogenous production of oestrogens and progestogens. The latter are potent respiratory stimulants. Oestrogens may affect breathing during sleep, either through a direct effect of the respiratory control system or by indirectly improving the stability of sleep. However, studies have shown that oestrogens may negatively affect ventilation, and, in fact, caution is recommended when administering HRT to women with asthma.(2)

Skin and mucosal symptoms
Oestrogen and progesterone receptors are found in the vagina, urethra, bladder and pelvic floor. This explains the changes in vaginal mucosal surface that occur with menopause. Menopausal women report a higher occurrence of vaginitis, pruritus and dyspareunia. Another effect of oestrogen deprivation is a decline in skin collagen content and in skin thickness.

Increase in coronary heart disease risk
During the reproductive years, women are protected from coronary heart disease due to increased levels of high-density lipoprotein (HDL) - an effect of oestrogen. After menopause the risk of coronary heart disease doubles for women as the atherogenic lipids (low-density lipoprotein) levels increase.

Osteoporosis
Osteoporosis is the reduction in bone mass or density accompanied by microarchitectural deterioration of the skeleton. Initially, this presents with little or no symptoms, but the condition has a long-term impact. Osteoporosis increases the risk of fractures, with the most serious injury being hip fracture. More than 10% of hip fracture patients die within a year of their injury.(3)

Presentation of HRT pharmaceutical products
HRT products vary in dosage presentation and formulation. Dosage forms include tablets, self-adhesive patches, implants, nasal spray and gel. Formulations consist of either an oestrogen component alone or a combination of an oestrogen and a progestogen (combined HRT). The combined HRT formulations are recommended for women with an intact uterus since the progestogen component reduces the risk of endometrial cancer. Combined formulations vary according to whether the progestogen component is presented for the last 12-14 days of the cycle (cyclical/sequential combined HRT), or whether the progestogen component is presented throughout the cycle (continuous combined HRT).(4)

Developments in the use of HRT
The principal use of HRT in menopause as a preventive therapy was based on offering relief from the occurrence of the multiple symptoms associated with oestrogen deficiency, particularly vaginal atrophy and vasomotor symptoms, and to prevent occurrence of osteoporosis. However, results from recent studies have led to changes in guidelines on the use of HRT. The risks of HRT outweigh the benefits presented when HRT is used to prevent osteoporosis in healthy women without symptoms of the condition. Alternative treatments for the prevention of osteoporosis, namely the bisphosphonates, are available.
A major disadvantage to the use of HRT, which has been documented since 1997, is the increase in breast cancer risk. This was confirmed by the Women's Health Initiative study (WHI), which was one of the studies on long-term use of HRT.(5-7)
The increased risk in breast cancer is related to the duration of HRT. However, on the other hand, the use of HRT reduces the risk of colorectal cancer.(6) The mechanisms by which hormone use might reduce the risk of colorectal cancer are still not clear.
The WHI study and the Heart and Estrogen/progestogen Replacement Study (HERS) have shown that HRT does not reduce the risk of a secondary coronary event, but that it does increase the risk of deep vein thrombosis and stroke.(6,8)
 
Conclusion
Recent developments in the use of HRT have resulted in changes in guidelines on their use in clinical practice. HRT still has benefits to offer, and it is essential that for each patient an individualised evaluation is carried out by the clinical team to assess whether the benefits for the individual patient outweigh the risks. In drawing up this evaluation of the impact of menopausal symptoms on quality of life, patient views on the risks presented, patient medical history and family history need to be considered.

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References

  1. Speroff L, et al. Clinical gynaecology, endocrinology and infertility. Philadelphia: Lippincott Williams and Wilkins; 1999.
  2. Kantola-Polo P, et al. Breathing during sleep in menopause: ­a randomized, controlled, crossover trial with oestrogen therapy. Obstet Gynecol 2003;102:68-74.
  3. Simon J, Mack G. Preventing ­osteoporosis and improving compliance with HRT. Contemporary OB/GYN [serial online] 2001. Available from URL: http://www.findarticles.com
  4. Tanna N. Hormone replacement therapy: an overview. Pharm J 2003;271:615-7.
  5. Collaborative group on hormonal factors in breast cancer. Breast cancer and hormone replacement therapy. Collaborative analysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997;350:1047-59.
  6. Writing group for WHI investigators. Risks and benefits of estrogen plus ­progestin in healthy menopausal women. JAMA 2002;288:321-33.
  7. Tanna N. Hormone replacement therapy: risks and benefits. Pharm J 2003;271:646-8.
  8. Hulley S, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605-13.

Resources
International Federation of Gynaecology and Obstetrics
W:www.figo.org
ObGynWorld
W:www.obgyn world.com
European Society of Gynaecology
W:www.seg-web.org
North American Menopause Society
W:www.menopause.org
National Osteoporosis Society (UK)
W:www.nos.org.uk 

Further reading
Hormone ­Replacement ­Therapy:
Yes or No
Kamen B.
Novato: Nutrition Encounter; 1996
Hormone Replacement Therapy Studies: A Reference Guide
Goulden S.
Jefferson: McFarland & Company; 2003
Hormone Replacement Therapy and the Skin
Brincat M, editor.
Oxford: Taylor & Francis Group; 2001