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The US Food and Drug Administration finally approved the injectable contraceptive Depo-Provera (DMPA) in October 1992, 25 years after its introduction. Women return to a health facility every 90 days for an intramuscular injection of 150 mg DMPA, which provides them 99% effective contraception. Menstrual changes and spotting are the leading reasons for DMPA discontinuation. Eventually, more than 50% of DMPA users develop amenorrhea. During the first year, women gain about 2 kg and weight increases as time passes. Weight gain is the second leading reason for DMPA discontinuation. DMPA may adversely affect glucose tolerance in women at risk for diabetes, but it does not affect cardiovascular or metabolic functions. It may increase the risk of osteoporosis. A rare side effect is convulsions. 1-10% of DMPA users have other central nervous system effects, such as headaches, dizziness, and depression. Itching and rashes may develop. Fertility returns within 1 year after discontinuation. DMPA is linked to low birth weight. It apparently does not harm breast-fed infants or hinder lactation. A World Health Organization study shows that DMPA users less than 35 years old experience a slight increase in breast cancer but a reduced incidence of endometrial cancer. Nurses are instrumental in guiding women as they choose DMPA and in informing them about its potential side effects, including breast cancer risk. They must screen women for pregnancy and evaluate their risk of breast cancer. They must determine whether women are able to return every 3 months for DMPA injections. Women who select DMPA must use other contraception, e.g., barrier protection, within the first 24 hours after initial injection. Nurses should counsel them about the likely menstrual changes to reduce the likelihood of dissatisfaction. They should recommend a daily dose of 1200 mg of elemental calcium and daily exercise of long bones to minimize the risk of developing osteoporosis.
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PMID:Depo-Provera. 849 47

Central nervous system (CNS) involvement by endometrial carcinoma is uncommon. Among 1069 patients registered for endometrial carcinoma at our institution between 1982 and 1994, 10 (0,9%) developed brain metastases. Median age at the time of CNS metastasis diagnosis was 59 years. Median interval between diagnosis of endometrial cancer and documentation of brain involvement was 26 months. Clinical manifestation of brain metastasis included headache (80%), motor weakness (50%), seizures (20%), confusion (10%), balance (10%), and visual disturbances (10%). All lesions (4 multiple, 6 single) were contrast enhancing on computed tomography (CT) scans, and were located in the cerebrum in seven cases, in the cerebellum in one case, and in both in two cases. The CNS was the only site of detectable disease in six patients with recurrent disease. Nine patients died and one is alive with disease 3 months after surgical resection of a single cerebral deposit. Median survival from diagnosis of brain metastases for the entire series was 1 month (range 1-83). Six patients receiving only steroids died within 1 month from the diagnosis. One patient received radiotherapy (survival, 3 months) and two underwent surgical resection of solitary metastasis followed by radiotherapy (survival = 28 and 83 months). Prognosis of patients with CNS metastases from endometrial carcinoma appears poor; however, in a selected group of patients early diagnosis followed by multimodal treatment may result in a palliation of the disease.
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PMID:Brain metastases from endometrial carcinoma. 862 15

Tamoxifen is a nonsteroidal anti-estrogen frequently used in breast cancer therapy. Side effects to tamoxifen are uncommon (2%) but should be recognized and detected early by careful follow-up. Tamoxifen adjuvant therapy is absolutely indicated in postmenopausal breast cancer with estrogen-receptor--positive nodes. Recently, this indication has been extended to negative-node postmenopausal breast cancer. Mild acute side effects are the most frequent: hot flushes, menstrual irregularity, nausea, headache, vertigo, minimal modifications in blood cell counts. However, more serious accidents can occur. Increased risk of thromboembolism is linked to a fall in the level of antithrombin III. Ocular toxicity can occur. If such ocular lesions are diagnosed early enough, they can be cured by promptly withdrawing treatment. For patients given tamoxifen, there appears to be a small increase in risk of endometrial carcinoma, especially if the daily dose is > 30 mg. This over-risk requires adequate detection based on sufficient knowledge of the usual tamoxifen-related modifications in the endometrium. Physicians should also be aware of two favorable effects. Tamoxifen therapy leads to decreased cardiovascular morbidity and mortality in postmenopausal women and is associated with a significant increase in lumbar bone density. Risk of interaction with oral anticoagulants has been reported. We discuss here practical steps in the follow-up of women treated with tamoxifen.
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PMID:[Surveillance of patients treated with tamoxifen]. 868 11

Progestins in oral contraceptives (OCs) produce potential complications, as well as noncontraceptive benefits, according to Robert A. Hatcher, MD, MPH, professor of gynecology and obstetrics, Emory University Medical School. Hatcher told CTU that lowering the progestin content in an OC may decrease complications, but could also decrease the benefits experienced by women. "The extent to which that will happen remains to be seen," he said. Hatcher cited the following potential complications of progestins in OC: hypertension; decreased levels of high density lipoproteins; acne; oily skin; headaches between pill cycles; dilated leg veins; pelvic congestion syndrome; thrombosis of superficial leg veins; gallstones; Monilia vaginitis; cholestatic jaundice; and depression, fatigue, and decreased libido. Progestins, according to Hatcher, also produce these noncontraceptive benefits: protection against PID; decreased dysmenorrhea; decreased menstrual blood loss, decreased iron deficiency anemia; protection against endometrial cancer; protection against fibrocystic breast disease, and fibroadenomas of the breast; decreased bleeding from fibroids; decreased growth of fibroids. When ovulation is suppressed, Hatcher emphasized, additional benefits that may occur include the following: decreased risk of functional ovarian cysts; elimination of mittleschmerz pain; decreased rick of ovarian cancer; protection against endometriosis.
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PMID:Potential risks, benefits of progestins in birth control pills outlined. 1231 83

FDA has approved medroxyprogesterone acetate as Depo Provera Contraceptive Injection, effective for 3 months in preventing pregnancy in women. In clinical studies, the drug's failure rate was less than 1%. However, physicians must ensure that patients receive injections on schedule to prevent pregnancy. The recommended dose is 150 mg administered every 3 months by deep, intramuscular injection in the gluteal or deltoid muscle. Most women in clinical studies of Depo Provera experienced menstrual irregularities. As use continued, amenorrhea became common, reported by 57% of the women by the end of a year of treatment. Other side effects included weight gain, headache, nervousness, abdominal pain or discomfort, dizziness, and asthenia. Physicians should administer the drug only to women found not to be pregnant, because fetal exposure may lead to low birth weight and other problems. Recent data have demonstrated that longterm use may contribute to osteoporosis, and the drug's manufacturer, the Upjohn Company of Kalamazoo, Michigan, will conduct additional research to study this possible side effect. Contraindications are similar to those for other contraceptives and include undiagnosed vaginal bleeding, known or suspected malignancy of breast, thromboembolic disorders, cerebral vascular disease, and liver dysfunction. Depo Provera was developed in the 1960s and has been approved for contraception in many other countries. When FDA first reviewed data on the drug in the 1970s, animal studies raised questions about its potential to cause breast cancer. Since then, longterm controlled clinical studies in other countries have shown a risk of breast cancer comparable to oral contraceptives, and no increased risk for ovarian, liver, or cervical cancer. The studies also showed that the contraceptive injection reduced the risk of endometrial cancer. FDA approved the drug October 29, 1992.
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PMID:3-month contraceptive injection approved. 1231 15

This report summarizes a meeting of the IPPF International Medical Advisory Panel (IMAP) held in November, 1986, at which information on steroidal oral contraception (OC), Acquired Immunodeficiency Syndrome (AIDS), and female sterility were discussed. Regarding the multiphasic OC now in use, the benefits to health and well-being outweigh the possible side-effects and infrequent complications. Use is associated with a lower incidence of pelvic inflammatory disease, 96-98% effective prevention of pregnancy, a protective effect against ovarian and endometrial cancer, and regulation of erratic menstrual cycles. Minor side effects include nausea, vomiting, dizziness, headache, fluid retention, and inter-menstrual spotting. Adverse effects are circulatory system disease, myocardial infarction, venous thromboembolism, elevated blood pressure, and liver disease. Data on possible carcinogenicity have been conflicting. For women over age 40 OCs should be prescribed with caution. IMAP also drew up recommendations to assist FPAs to play a more active role in controlling the spread of AIDS. An effective program of Information and Education is of primary importance, targeting family planning workers and clients, teachers, parents, and employers. Wide promotion of condom use is a priority. Studies in Africa have revealed a major epidemic of AIDS, with the major mode of transmission heterosexual. The only immediate practical step in prevention of spread is by changes in sexual behavior. The last topic discussed is that of sterility in African women. The naturally occurring level of infertility expected in all populations of women is 3%; high levels in Africa vary by region from 3-32%. These levels of sterility are acquired through infection with Neisseria gonorrheae and Chlamydia trachomatis. Silent infection of women with Chlamydia make treatment especially difficult.
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PMID:Statement on steroidal oral contraception. 1234 Sep 76

Depot medroxyprogesterone acetate (DMPA, Depo-Provera) is used for contraception by 8-9 million women in more than 90 countries, including the US, as of January 1993. Pharmacologically active levels of DMPA persist for 3-4 months following injection. A 150 mg dose is used most often for high contraceptive efficacy every 3 months. Norethindrone enanthate (NET-EN, Noristerat) is somewhat less widely used and is not marketed in the US. Injectables act primarily by inhibiting ovulation, lowering the levels of follicle-stimulating hormone and luteinizing hormone. Approximately 50% of women using DMPA for 1 year report amenorrhea whose occurrence is less frequent with NET-EN. Menstrual changes are the most frequent causes of discontinuation of injectables. In cases of heavy bleeding it is appropriate to undergo gynecological examination to rule out unrelated conditions, such as vaginitis, cervicitis, or cervical lesions. The use of conjugated estrogen (12.5-2.5 mg daily) for 10-21 days will minimize bleeding. Some women using injectables experience headache, dizziness, bloating of the abdomen or breast, and mood changes. Long-term use of DMPA or NET-EN can often result in 1-3 kg weight gain. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives was launched in 1979 to examine cancer risks with the use of DMPA in Thailand, Mexico, and Kenya. The relative risk of breast cancer was 1.21, which was statistically not significant. In women diagnosed with breast cancer under age 35, short-term exposure to DMPA was associated with a slightly increased breast cancer risk, which, however, was not associated with duration of use. DMPA dramatically lowers the risk of endometrial cancer for at least eight years following discontinuation of its use. DMPA did not alter the risk of cervical cancer. Fertility returns in 70% of former users within 12 months; it is suitable for postpartum and lactating women, and provides other noncontraceptive benefits.
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PMID:Injectable contraception: the USA perspective. 1234 20

Oral contraceptives (OC) are either composed of a combination of an estrogen derivative (usually ethinly estradiol) and a progestogen, or they contain a progestogen only. OC are characterized by a high effectiveness and have a low failure rate if taken correctly. Most women tolerate OC relatively well, but adverse effects do occur which are driven by the estrogen dose as well as by the type of progestogen. The most frequently reported adverse effects are nausea or vomiting, breast tenderness, headache or inbalanced mood, but these unwanted side effects are often transient. The fear of weight gain of many OC users is not necessarily supported by data from studies which report relatively little differences in body mass index on average during OC use. Nevertheless, substantial weight gain can occur in individual women. The widely discussed fear of breast cancer is also not justified, and the risk of developing ovarian or endometrial cancer is reduced for women who use OC on a regular basis. Venous thromboembolism (VTE) is the adverse effect with the greatest potential for serious harm if pulmonary embolism develops. This rare, but potentially dangerous adverse effect of OC has been discussed emotionally for many years and keeps attracting a lot of public interest. VTE is rare in young women, but the VTE risk is increased two- to sixfold for OC users as compared to non-users. The VTE risk increases with increasing estrogen dose, is highest in the first year of use, and is higher for OC from the third generation (containing desogestrel, gestodene or norgestimate) than for OC from the second generation (containing levonorgestrel) or than for the progestogen-only pill. According to most studies, OC containing the progestogens drospirenone or cyproterone acetate are similar with regard to VTE risks than OC from the third generation. Individual genetic susceptibility affecting the clotting system plays a major role in the risk of developing VTE in combination with OC, and smoking is also an important contributing factor to an increased VTE risk for women using OC. It is important that doctors and pharmacists inform new users of OC about potential health risks of OC use, and that the personal and family history of previous health risks is assessed thoroughly in order to rule out that important and relevant contraindications are present when a women starts taking OC.
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PMID:[Health risks of oral contraceptives]. 2165 94

Pogostemon cablin (PC) is a traditional herbal medicine used in the treatment of the common cold, nausea, diarrhea, and even for headaches and fever. However, the mechanisms underlying the anti-proliferative activity of PC in endometrial cancer (EC) cells have yet to be fully elucidated. This study investigated the anticancer effects of an aqueous extract of Pogostemon cablin (PCAE), specifically induced apoptosis in EC (Ishikawa) cells. Proliferation of EC cells following exposure to PCAE was assessed by an MTT assay. DNA content and the induction of cell cycle apoptosis were analyzed by flow cytometry (FACS Calibur). Protein caspase-3 and, -9 as well as AIF were investigated using Western blot. Our results demonstrate growth inhibition of Ishikawa cells by PCAE. Furthermore, caspase-3 activity caused PCAE-treated cell lines to accumulate in apoptosis. Gene expression profiling (GEP) results further suggest that, in addition to its known effects with regard to EC prevention, PCAE may also exert antitumor activity on established EC cells. Many previous studies have identified the chemo-preventive effects of natural plant materials and the potential role of these materials in chemotherapy. This current study used human EC Ishikawa cells to investigate the anti-tumor effects of PCAE in EC cells. Our results demonstrate that PCAE inhibits the growth of cancer cells and induces apoptosis, which suggests the potential applicability of PCAE as an antitumor agent.
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PMID:Induction of Apoptosis in Endometrial Cancer (Ishikawa) Cells by Pogostemon cablin Aqueous Extract (PCAE). 2604 64

In the absence of significant extracranial disease, patients with solitary brain metastases have shown benefit with resection. Brain lesions due to endometrial cancer are uncommon, and the only described skull base involvement is limited to the pituitary gland. We report the case of a 60-year-old female with endometrial cancer who presented with weeks of right cheek pain and numbness that was accompanied by headaches. We describe the magnetic resonance imaging (MRI) findings and surgical resection of a solitary endometrial metastasis involving the infratemporal fossa, middle fossa, cavernous sinus, trigeminal nerve, and nasal sinuses. Due to extensive nasal and lateral involvement, a combined open and endoscopic approach was planned. The patient was discharged home without complication. She underwent adjuvant radiotherapy. Despite its suspected indolent course, intracranial endometrial adenocarcinoma metastases are gaining higher prevalence. This case report documents the first direct neural spread of an endometrial primary, and highlights the potential for extra-axial sites of metastasis.
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PMID:Combined Open and Endoscopic Endonasal Skull Base Resection of a Rare Endometrial Carcinoma Metastasis. 2947 14


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