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You are welcome to a new column in Sexual Health Matters that will navigate the medical world to flag recent development in sexual Health issues. There will opportunity to take part in problem based medical exercises. The columnist welcomes feedback from readers through the feed back e-mail.
New potential problems of Hormone Replacement Therapy (HRT).
Recent studies have indicated that the use of HRT may affect sensitivity of screening mammography. The Australian study looked at the sensitivity, specificity and small-cancer detection rate in 103770 asymptomatic HRT users [1]. The sensitivity of screening mammography was lower in HRT users (64.8%, 95% confidence interval [CI] 58-720) than in non-users (77.3 %, 95% CI 74-81). If mammography had the same sensitivity in both users and non-users, an additional 23 cancers (20% more cancers) would have been detected by screening HRT users. In the target group (50-69 years), the sensitivity was 64.3% (57-72%) in HRT users and 79.8% (76-84%) in non-HRT users. The rate of false negative screen was higher in HRT users than in non-users [odds ratio 1.60 (1.04-2.21)]. The converse is true in women who were not diagnosed with cancer in the 2-year research interval, i.e. HRT users were more likely to have a false positive result.
It is established that postmenopausal HRT is associated with breast cancer from age 50 with a risk of 2.3% per year of use in accordance with the collaborative group. Preliminary study suggested an association between HRT and ovarian cancer after 10 years of use. Postmenopausal oestrogen (E2) raises the serum oestradiol and oestrone levels and decreases the secretion of gonadotrophins. These decreasing levels of gonadotrophins were associated with significantly higher risk of ovarian cancer [2]
A more recent study from the American Cancer Society in Atlanta, Georgia confirmed that postmenopausal women who used E2 for at least 10 years were twice as likely to develop ovarian cancer as their peers who did not take it, with the risk persisting long after stoppage. Women who used E2 for 10 or more years but stopped taking it remained at risk 29 years later [3]. The latter Group followed up 212000 women for 14 years from 1980s. Twenty two percent had used E2 replacement therapy. Among women who had used this regimen for at least 10years, the rate of death from ovarian cancer was 0.64% (64.4 per 100,000 women). This was compared with 0.38% (38.3 per 100,000 women) that discontinued E2 treatment after at least 10 years of use and 0.26%(26.4 per 100,000 women) that never used the treatment. Using E2 for less than 10 years did not increase risk of developing ovarian cancer. The interaction between E2 use and ovarian cancer is not fully known but might be related to low levels of postmenopausal gonadotrophins.
It is reassuring that this relationship is true for oestrogen monotherapy which was the regimen of the early 1980s and not combination therapy which is what women take today.
The learning point is that women should be given information of the relationship between mammograhic screening accuracy and HRT, Oestrogen monotherapy and risk of ovarian cancer in women with ovaries when they are making decisions about whether to start HRT.
[1] Kavanagh et al; Anti—cancer Council of Australia, Carlton South, Vic Australia. Lancet 2000; 355[9200]: 270-274.
[2] (JAMA 1995; 274:1926-30).
[3] Rodriguez C et al; Oestrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA 2001 ; 285: 1460-5)
Pulsed Oestrogen Therapy - A revolution in HRT Management.
The latest in the HRT market is Intranasal spray which was being investigated for clinical use. S21400 (Aerodiol) is a new aqueous nasal spray containing 17b-Oestradiol, conjugated to a novel polysaccharide excipient that allows for the aqueous solubility of the steroid hormone [1]. Intranasal oestrogen relieves hot flushes in a dose-dependent fashion. From the current data, S21400 may be safely tolerated for a relatively short duration and used in a dose-dependent fashion to relieve menopausal symptoms, especially hot flushes. Long-term data regarding safety and effects on prevention of osteoporosis, cardiovascular and mammary systems are untested [2]. This product was launched in the UK on 8th May 2001.
There was no significant interaction to smoking and remarkably there were no known non-absorbers. The optimum dose is 300µg /day usually administered in two 150µg sprays per day. One Flask contains 62 doses equivalent to a 30-day prescription. The NHS price is Ł6.77.
[1] John Studd et al 1999: Efficacy and acceptability of intranasal 17_-oestradiol for menopausal symptoms: randomised dose-response study. The Lancet Vol. 353 (9164): May 8, 1999.
[2] Scheiber MD. Reduction in menopausal symptoms was similar with intranasal and oral Oestradiol. Evidence-based Obstetrics and Gynaecology 2000; 2, 25.
Hormonal Contraceptive Vaginal Ring - A revolution in Contraception.
Recent multicentre, Scandinavian Study published by Roumen et al [1] evaluated a new contraceptive vaginal ring in 1145 women for 12 months. The active ingredients were 120_g of etonogestrel and 15_g of ethinyl oestradiol administered daily over a period of three weeks ON and one week OFF (ring-free period). This method produced good cycle control, was found to be efficacious with a PEARL index of 0.65 and women found it acceptable with compliance in 90.8% of 12,109 cycles (928 women-years). It remains to be seen whether such modality of contraception would be equally attractive amongst the UK population.
[1] Roumen et al 2001. Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Human Reproduction, vol 16, No3, 469-475, March 2001.
HAART and Gene therapy for HIV
The current gold standard for managing HIV, the use of Highly Active Antiretroviral Therapy (HAART) has dramatically changed the therapeutic landscape for HIV infected patients. This involves a combination of Nucleoside analogue reverse transcriptase inhibitors (Nucs), Non-nucleoside analogues (Non Nucs) and Protease inhibitors (PIs). The two main targets for these agents are the processes of reverse transcription and protease cleavage which are brief events, compared with cell wall synthesis in bacteria creating a very narrow therapeutic window. This necessitates consideration of alternatives.
Gene therapy to date has not attracted a lot of interest in the management of HIV infection. However, things are changing. The hypothesis that human race has evolved to protect itself against invading pathogens and given time, especially in areas of high disease endemicity and low current antivirals, such as sub-saharan Africa, one may see in the near future such genetic selection emerging. Gene therapy is therefore deemed to mimic this process and speeding it up largely by administration of effective, non-toxic, non-heritable genetic modulators.
Gene therapy is classically divided into two main types; those where nucleic acid is the effector molecule and those where it is protein. A second classification based on the mode of action of the gene therapy has been used in an interesting comprehensive review article by Lever [1]. Thus, there are DNA and RNA based antisense molecules, Ribozyme and Decoy RNAs, Transdominant negative proteins, Suicide genes, and Immunomodulatory proteins. The scientific basis of this exciting strategy is reviewed in this article [1] .
[1] Lever AML 2001. Gene Therapy for HIV; Sexually Transmitted Infections 77:93-96 (2001).
SHASTD Annual Conference
This year's SHASTD annual conference was held at Bishop Stortford 18-20th April. Attendance was very good. The meeting covered topics such as sexual health services for young people, drug assisted rape, a model for health adviser practice, early syphilis, and a debate on whether health advisers should be proactive in partner notification. There were also a variety of workshops, an oral presentation and the AGM. Next year the conference will be held in Newcastle, April 2002. This will be a great opportunity for our local health advisers to attend. As a Northern region we will be hosting a SHASTD meeting and study day Saturday 8th September, focussing on the health adviser role of partner notification.
Lynn Wilson
Health Adviser/Northern Region SHASTD Rep
Forthcoming Events
1. 15th-16th October 2001 - Grimsby Basic Transvaginal Ultrasound Workshop. This will take place at the Postgraduate Medical Education Centre, Diana Princess of Wales Hospital, Grimsby. Tel 01472 874111 for details.
2. 7th November 2001 - Cleveland HIV Update. This will take place at the Postgraduate Medical Education Centre, James Cook University Hospital, Middlesbrough. Tel. 01642 854548 for details.
©2001 Sexual Health Matters. Published Quarterly by Express Print Works, Middlesbrough,
UK
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