SEARCHLIGHT
Navigating the Global Medical Network
Of Sexual Health Issues for Sexual Health Matters
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You are welcome to this column in Sexual Health Matters that will regularly navigate the medical world to flag recent development in Sexual Health issues. There will be opportunity to take part in regular problem based searchlight medical exercises. The columnist welcomes regular feedback from readers through the feed back e-mail. Enjoy your reading.
SERMS and SPRMS :Pros and Cons
(a) Role of Selective Progesterone Receptor Modulators [SPRMs] and Progesterone antagonists in Reproduction
A review of progesterone agonists and antagonists by David Olive in Obstetrical and Gynaecological survey1 highlighted recent progress in reproductive health. Progesterone antagonists act to counteract the effect of progesterone whilst SPRMs have both agonist and antagonist activities depending on site of action. SPRMs have been studied for their effect on a number of target organs including, endometrial growth, and endometrial vascular development, the hypothalamic-pituitary-ovarian axis and cervical integrity. Such research has led to a number of potential clinical applications.
Progesterone antagonists are well established in their use for termination of pregnancy, induction of labour, the treatment of endometriosis, fibroids and contraception. They may also work well to soften and dilate the cervix before surgery.
On the other hand SPRMs seem to have a diminished capacity for induction of abortion and they are unlikely to subserve a cervical softening or dilating role. They may prove useful in the treatment of endometriosis, fibroids, postmenopausal hormone replacement therapy and the treatment of dysfunctional uterine bleeding. Finally, these compounds may aid investigators in unravelling many of the nuances of the role of progesterone in reproductive function.
Are SERMS associated with adverse events?
Selective oEstrogen Receptor Modulators are novel compounds that bind to the oestrogen receptor and have mixed agonistic and antagonistic activities. Recently, an increase in urinary incontinence has been reported with hormone replacement therapy use. A decrease in surgical procedures for pelvic floor relaxation has been recently reported with raloxifene, a selective oestrogen receptor modulator that is not uterotropic. Levormeloxifene is a selective oestrogen receptor modulator that was developed for the purpose of the treatment and prevention of postmenopausal osteoporosis. Levormeloxifene shows a significant risk of gynaecologic adverse events that include uterovaginal prolapse, urinary incontinence, leukorrhoea, increased endometrial thickness, and increased uterine size. In a prospective multicentre study of postmenopausal women with osteoporosis, The patients were randomised to blindly receive placebo or Levormeloxifene 0.5mg or 1.25mg daily as part of a 3-year osteoporosis study 2.
Among 2924 women who were studied, those treated with Levormeloxifene had a marked increase compared with placebo in leukorrhoea (30% vs. 3%), increased endometrial thickness on ultrasound scan (19% vs. 1%), enlarged uterus (17% vs. 3%), uterovaginal prolapse (7% vs. 2%), urinary incontinence (17% vs. 4%), increased frequency of micturition (9% vs. 4%), lower abdominal pain (17% vs. 6%), hot flushes (10% vs. 3%), and leg cramps (6% vs. 0.8%). All of these differences were highly statistically significant with a probability value of .0001 for each.
The study was halted after 10 months because of the large number of gynaecologic and other adverse events.
I David L.Olive . Role of progesterone antagonists and New Selective Progesterone Receptor Modulators [SPRMs] and in Reproductive health. Obstetrical and Gynecological Survey 2002; 57(11):S55-S63
2. Steven R. Goldstein, Nayan Nanavati, Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study Am J Obstet Gynecol 2002;187:521-7
Substance abuse and Amniotic Fluid Index and Methadone trough levels in pregnancy
(a) AFI and substance abuse.
There is a recognised association between maternal drug use and fetal central nervous system depressive effects as manifested by decreased biophysical profile scores. Drug effects on the amniotic fluid index (AFI), is one variable of the biophysical profile that is not well documented. Panting-Kemp et al 1 determined these effects in 63 consecutive toxicology-positive cases over an 18-month period. . Although there was no significant difference between mean AFI values, the incidence of polyhydramnios (AFI >24 cm) was significantly higher in substance users (28.6%) than in control patients (3.9%) (P < .005). It was therefore concluded that maternal substance abuse is associated with a significantly higher incidence of polyhydramnios and should be considered a possible etiologic factor in women with apparent idiopathic polyhydramnios.
(b) Methadone trough levels in pregnancy. What serum trough level of methadone is adequate to prevent withdrawal symptoms in heroin-addicted pregnant women?
Does the methadone serum trough level in symptomatic women with withdrawal symptoms differ from that of asymptomatic women?
These were the two research questions that Drozdick et al 2 from Philadelphia set out to answer in a study involving pregnant women addicted to heroin who were followed up prospectively between March 1, 1999, and March 1, 2000, in a special multidisciplinary methadone programme. These patients’ methadone serum trough 20-24 hours after last dose level was checked at regular intervals throughout pregnancy. Methadone levels were kept blinded from clinicians and their doses were increased only according to withdrawal symptoms. Methadone levels of asymptomatic (without withdrawal symptoms) women were compared with methadone serum trough levels of symptomatic (with withdrawal symptoms) women.
Mean methadone serum trough level was 0.295 ± 0.16 mg/L in asymptomatic women and 0.175 ± 0.11 mg/L in symptomatic (P < .001). The mean methadone dose in asymptomatic patients was 101 ± 42 mg versus 114 ± 43 mg in symptomatic patients (P = .1). By receiver operating characteristic curve, the best differentiating methadone trough level between asymptomatic and symptomatic women was 0.24 mg/L. Continuing drug abuse, maternal weight, or gestation age when methadone serum trough level was drawn did not influence these differences in methadone serum trough levels between asymptomatic and symptomatic women.
Mean methadone serum trough level in asymptomatic pregnant women is approximately 0.3 mg/L, and levels of 0.24 mg/L or greater should be considered adequate to prevent withdrawal symptoms in pregnancy. Knowledge of these levels will help management of the frequently non-compliant heroin-addicted pregnant woman. Appropriate daily dosing to achieve these levels is usually between 50 and 150 mg methadone, with the occasional need for even higher doses in the third trimester.
1. Andrea Panting-Kemp, Tuan Nguyen and Lony Castro. Substance abuse and
polyhydramnios . Am J Obstet Gynecol 2002; 187:602-5.)
2. John Drozdick III, Vincenzo Berghella, MaryKay Hill, Karol Kaltenbach. Methadone tough levels in pregnancy. Am J Obstet Gynecol 2002; 187:1184-8.
The benefits of insulin sensitising drugs in polycystic ovary syndrome beyond ovulation induction
Insulin sensitising agents, such as metformin are becoming increasingly popular in the management of PCOS as they act directly at the pathogenesis of the syndrome and help correct both metabolic and endocrine problems. The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity. In the article by Stadtmauer et al 1 the data supporting the effect of metformin on improving hyperandrogenaemia and hyperinsulinaemia in PCOS patients were summarised. It was proposed that metformin benefits PCOS patients undergoing gonadotrophin therapy and IVF(in-vitro fertilisation) as well as ovulation induction. They also advocate the use of insulin sensitising drugs to reduce miscarriage rates, and risks associated with coronary artery disease, gestational diabetes and obesity.
1. Laurel A. Stadtmauer1, Benjamin C. Wong and Sergio Oehninger. Should patients with polycystic ovary syndrome be treated with metformin? . Benefits of insulin sensitising drugs in polycystic ovary syndrome-beyond ovulation induction. Hum Reprod 2002 17: 3016-3026
©2001 Sexual Health Matters. Published Quarterly by Express Print Works, Middlesbrough,
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