Abstract
Researchers suggest that the risk of ovarian cancer should be taken into account by women considering the use of hormone therapy.
Previous studies have suggested that women taking postmenopausal hormone therapy (HT) may be at an increased risk of ovarian cancer. Limited data are available regarding the differential effects of formulations, regimens and routes of administration. However, a new study published by researchers at Rigshospitalet, Copenhagen University, Denmark, sheds light on the link and provides support for the finding that women taking HT (or those who have previously taken it) are at a higher risk of ovarian cancer compared with never-users.
Lina Steinrud Mørch and colleagues investigated 909,946 women who did not have hormone-sensitive cancer or who had not had both ovaries removed, enrolling Danish women aged 50–79 years from 1995 to 2005 through individual linkage to Danish national registers. Prescription data from the National Register of Medicinal Product Statistics was used and provided individually updated information on HT use. In addition, the National Cancer Register and Pathology Register provided ovarian cancer incidence data.
At the end of an average of 8 years of follow-up, 63% of the women had not been taking HT, 22% had used HT in the past and 9% were current users of HT. Among the current users, 46% had used HT for more than 7 years. During the follow-up, 3068 ovarian cancers were detected, 2681 of which were epithelial tumors. Current users of HT were found to be at a 38% increased risk of ovarian cancer overall compared with never-users.
Limiting the results to epithelial ovarian cancer, the researchers demonstrated the relative risk among current HT users to be increased by 44% compared with women who had never used HT. In addition, previous HT users were found to have a 15% increased risk compared with never users.
The results of the study demonstrated that the risk for ovarian cancer and epithelial ovarian cancer did not increase signifcantly with increasing durations of HT use. However, the researchers found that a longer time since last HT use was correlated with a decline in the risk of ovarian cancer.
Commenting on the findings, Mørch noted: “The risk among women taking hormones was increased regardless of the duration of use, the formulation, the estrogen dose, regimen, progestin type or route of administration.”
“The study suggests that no type of hormone seems safe regarding the risk of ovarian cancer. If a woman has a special predisposition for ovarian cancer, she should consider not taking hormones,” Mørch continued.
The absolute risk indicated approximately one extra ovarian cancer for approximately every 8300 women taking HT each year. “If this association is causal, use of hormones has resulted in roughly 140 extra cases of ovarian cancer in Denmark over the mean follow-up of 8 years (i.e., 5% of the ovarian cancers in this study). Even though this share seems low, ovarian cancer remains highly fatal, so, accordingly, this risk warrants consideration when deciding whether to use HT,” the authors write in the Journal of the American Medical Association.
“The risk of ovarian cancer is one of several factors to take into account when assessing the risks and benefits of hormone use,” the authors conclude.
Source: Mørch LS, Løkkegaard E, Andreasen AH, Krüger-Kjaer S, Lidegaard O: Hormone therapy and ovarian cancer. JAMA 302(3), 298–305 (2009).
New study identifies women who may be at risk of weight gain following use of an injectable contraceptive
Researchers at the University of Texas Medical Branch at Galveston (UTMB; TX, USA) have investigated the link between administration of the injectable contraceptive, depot medroxyprogesterone acetate (DMPA; Depo-Provera) and weight gain. Previous studies conducted earlier this year suggested that women who use DMPA gain significant weight compared with those using oral or nonhormonal contraception. However, the findings from the present study, published in the August issue of Obstetrics and Gynecology, demonstrate that not all women who use DMPA gain weight.
Researchers investigated the effects of DMPA use on weight gain in 240 women aged 16–33 years. All subjects were assessed before initiating contraception and followed-up every 3 months for 36 months. Researchers also accounted for several factors for weight gain such as age, race, baseline obesity prior to DMPA use, as well as smoking and exercise level.
Upon analysis, it was found that approximately a quarter of DMPA users had gained more than 5% of their bodyweight within 6 months (defined as early weight gain). Furthermore, these women continued to gain a significant amount of weight over the next 30 months compared with women who gained a regular amount of weight (0.35 kg/month compared with 0.08 kg/month, respectively; p < 0.001).
It is also interesting to note that previous studies have associated weight gain as a result of birth control measures with a higher BMI; however, the current study suggests that a BMI of less than 30 is a significant risk factor for weight gain.
“The amount of DMPA administered to a woman does not change based on weight, as occurs with some medications,” explained Abbey Berenson, corresponding author of the study and professor in UTMB's department of obstetrics and gynecology. “The drug may be more concentrated in the tissue of a woman with a BMI under 30 and may contribute to excessive weight gain, but more research is needed.”
The molecular mechanism of DMPA-related weight gain still remains to be elucidated. Possible mechanisms include an alteration in the body's metabolism of glucose and/or an interference with insulin action. Some also theorize that the drug may cause increased caloric intake, thus resulting in an increase in weight gain. However, further research is needed to confirm these hypotheses.
“Some also theorize that the drug may cause increased caloric intake.”
These results indicate that most DMPA users who gain weight appear to experience a 5% weight increase within the first 6 months of DMPA use. It is hoped that data from this study will help physicians to predict who is at a higher risk of gaining weight and take appropriate action. The researchers also recommend that physicians carefully monitor weight at each 3-month follow-up visit. For patients who appear to be gaining weight within this time, a different birth control method should be recommended.
Source: Le YC, Rahman M, Berenson AB: Early weight gain predicting later weight gain among depot medroxyprogesterone acetate users. Obstet. Gynecol. 114, 279–284 (2009).
in brief…
Kurth T, Schürks M, Logroscino G, Buring JE: Neurology (2009) (Epub ahead of print).
A total of 27,798 US women aged 45 years or older, who were free of cardiovascular disease (CVD) and for whom information on lipids and migraine frequency was available, were enrolled in a prospective trial to investigate the association between migraine and CVD. Migraine frequency was categorized as less than monthly, monthly, and more than or equal to every week. Incident CVD was confirmed after medical record review. Of the 3568 women with active migraine at baseline, 75.3% reported a migraine frequency of less than monthly, 19.7% monthly, and 5.0% more than or equal to every week. During 11.9 years of follow-up, 706 CVD events occurred. Compared with women without migraine, the multivariable-adjusted hazard ratios among active migraineurs for CVD were 1.55, 0.65 and 1.93 for an attack frequency less than monthly, monthly, and more than or equal to every week, respectively. The authors conclude that the association between migraine and cardiovascular disease varies by migraine frequency. Significant associations were only found among women with migraine with aura.
Jamieson DJ, Honein MA, Rasmussen SA et al.: Lancet (2009) (Epub ahead of print).
With the aim of improving surveillance, data from the US CDC was used to obtain information regarding cases and deaths in pregnant women with pandemic H1N1 virus infection in the USA. From 15 April to 18 May 2009, 34 confirmed or probable cases of pandemic H1N1 in pregnant women were reported to US CDC from 13 states. Of these, 11 (32%) women were admitted to hospital for treatment. The estimated rate of admission to hospital for pregnant women with confirmed or probable swine flu was more than four-times higher than that for the general population, at 0.32 per 100,000 pregnant women versus 0.076 per 100,000 population at risk. Between 15 April and 16 June, 2009, six deaths in pregnant women were recorded; all were among women who had developed pneumonia and acute respiratory distress syndrome that required mechanical ventilation. The authors suggest that pregnant women may be at an increased risk for complications from pandemic H1N1 virus infection and note that their data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs.
Research suggests uterine cells produce their own estrogen during early pregnancy
For decades, it has been assumed that the ovary alone produces steroid hormones during pregnancy. However, new research in a murine model, published in Proceedings of the National Academy of Sciences, demonstrates that once an embryo attaches to the uterine wall, the uterus is able to locally synthesize the estrogen required to sustain the pregnancy, providing evidence that the uterus may act as an endocrine organ.
“It is the local estrogen that is critical in maintaining the growth of blood vessels within the uterus,” explains Amrita Das, doctoral student and co-author of the study from the University of Illinois, IL, USA. The researchers, led by Indrani Bagchi, found that after an embryo implants itself in the uterus, this locally produced estrogen acts in conjunction with progesterone from the ovaries to enable the differentiation of uterine stromal cells (a process termed decidualization) and to promote the growth of blood vessels that support the early development of the embryo. During decidualization, murine uterine stromal cells were found to increase their expression of P450 aromatase, a key enzyme that works with others to convert androgens to estrogen.
“…once an embryo attaches to the uterine wall, the uterus is able to locally synthesize the estrogen required to sustain the pregnancy…”
The production of uterine estrogen was found to be able to support the growth and differentiation of the tissue and blood vessels even in an ovariectomized pregnant mouse model, although progesterone supplementation is required to maintain the pregnancy. Using letrozole, a specific aromatase inhibitor, was demonstrated to block the stromal differentiation process.
Bagchi explains that there are advantages to producing estrogen locally in the uterus where it is needed: “During pregnancy, the ovaries would need to secrete a high level of estrogen to ensure that the right amount of estrogen is present in the uterus to support decidualization… You can imagine that if the estrogen level goes high systemically, it could have a deleterious effect on pregnancy itself by antagonizing the progesterone action.”
Source: Das A, Mantena SR, Kannan A, Evans DB, Bagchi MK, Bagchi IC: De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis. Proc. Natl Acad. Sci. USA (2009) (Epub ahead of print).
US FDA grants approval for single-dose emergency contraception
Teva Pharmaceutical Industries Ltd, Israel, has announced that the US FDA has approved its new drug application for a new one-pill formulation of the emergency contraceptive Plan B® – Plan B® One-Step emergency contraception (levonorgestrel tablet, 1.5 mg) – simplifying the use of this important pregnancy-prevention treatment and representing “a positive step forward for women's health”, according to The American College of Obstetricians and Gynecologists (ACOG).
Earlier this year, after a federal district court in New York, USA, ordered the FDA to make emergency contraception available without a prescription to women under 18 years of age, the FDA lowered the age for nonprescription emergency contraception to 17 years, and is now expanding over-the-counter access to Plan B One-Step for consumers aged 17 years or older, with women younger than age 17 years still requiring a prescription.
“ACOG again urges the FDA to withdraw the age restriction altogether and eliminate the behind-the-counter status for emergency contraception.”
Amy Niemann, General Manager and Senior Vice President of Teva Women's Health comments, “Emergency contraception is more effective the sooner it is taken, and, with Plan B One-Step, women can now act quickly and take it right away when the unexpected happens.”
A statement from ACOG states that: “Although ACOG is encouraged by recent FDA actions, it reiterates its long-held position that there is no valid scientific or medical reason to impose an age restriction on the availability of emergency contraception because it is safe and effective for adolescents and women of all ages. ACOG again urges the FDA to withdraw the age restriction altogether and eliminate the behind-the-counter status for emergency contraception.”
Source: Teva Pharmaceutical Industries Ltd (www.tevapharm.com/pr/2009/pr_860.asp) The American College of Obstetricians and Gynecologists (www.acog.org)