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The acceptability of 2 and 3 month injectable contraceptives was assessed and compared, and the acceptability of the injectables was further compared with that of oral contraceptives (OCs) and IUDs among a random sample of women, who attended a clinic in Alexandria, Egypt. The study was conducted by the University of Alexandria. The sample included 100 acceptors of the 2-month injectable, norethisterone oenanthate (NET-O EN), 100 acceptors of the 3-month injectable, depo-medroxy pregesterone acetate (DPMA), 60 OC acceptors, and 60 IUD acceptors. The women were interviewed prior to treatment and 2 or 3 times during the 6 months following their initial acceptance of the methods. Women who discontinued at any time during the 6-month period were interviewed concerning their reasons for discontinuing. The data was analyzed by calculating means and % distribution and by testing for significance. The percent lost to follow up was 12% for the NET-O EN group, 12% for DPMA users, and 0% for IUD and OC acceptors. The mean age of the acceptors was 30.4 years for NET-O EN, 30.7 years for DMPA, 28.3 years for OCs, and 25.2 years for IUDs. For these acceptor groups, the respective mean number of years of schooling was 6.1, 5.2, 7.2, and 7.5, and the respective mean number of pregnancies was 5.6, 5.4, 3.8, and 2.9. All 320 of the women were married, and 319 were Muslim. 99.4% lived in urban areas. 10% had no living male children, and 23.7% had no living female children. 2/3 of the injectable acceptors previously used 2 or more fertility control methods. A higher percent of IUD and OC acceptors, compared to injectable acceptors, reported using only 1 or no previous method. More than 1/2 of the injectable acceptors reported disruptions in their normal bleeding patterns. NET-O EN acceptors were more likely to experience heavy or prolonged bleeding while DPMA acceptors were more likely to report amenorrhea or a decreased flow. IUD acceptors were also bothered by bleeding problems. Almost all the women who reported changes in bleeding patterns were unhappy about the changes. Many of the women who reported amenorrhea worried that they might be pregnant. Women who experienced heavy or unpredictable bleeding worried about anemia and complained that bleeding interfered with their daily routines. 47.6% of the women reported weight gains, but this was generally viewed as an advantage. Nausea was the major side effect associated with OC use. 32% of the OC users, 28.0% of the NET-E ON users, 30.0% of the DMPA users, and none of the IUD users reported nausea. For all 4 groups, convenience and effectiveness were the major advantages the women attributed to their chosen method. Continuation rates were 68% for NET-O EN, 70% for DMPA, 75% for OCs, and 75% for IUDs. The major reason for discontinuation of injectables was bleeding problems. Among injectable users, a higher proportion of discontinuers (49%) than of continuers (20%) reported amenorrhea. The findings suggest that continuation for injectables could be improved if patients were given more detailed information about possible side effects and if they were advised to return to the clinic for treatment of any symptoms they experience.
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PMID:Acceptability study of the two versus three monthly injectable contraceptives. 1217 96

About 8 million women use the long acting injectable contraceptive depot-medroxy-progesterone acetate (DMPA) and norethisterone enanthate (NET-EN). These progesterone only injectables are not dependent on sexual activity and are easy to administer. Yet they are not always well accepted since they can interfere with menstrual bleeding and often induce amenorrhea. Researchers find that adding estrogen to DMPA and NET-EN treats these irregularities. They must use esters with limited action to protect the endometrium from constant estrogens, however, which requires monthly injections. Thus bleeding occurs once a month just like the normal menstrual cycle. Clinical trials in China of Injectable No. 1 (250 mg 17-alpha-hydroxyprogesterone caproate and 5 mg estradiol valerate) show that it has few side effects and is acceptable. Other trials in China are evaluating monthly injectables with NET-EN or megestrol acetate. Numerous developing countries often as WHO's Special Programme of Research in Human Reproduction for effective, safe, and fully studied monthly injectables. WHO operates under a 2 part strategy: optimum improvement of HPR 102 (50 m NET-EN and 5 mg estradiol valerate) and Cyclofem (25 mg DMPA and 5 mg estradiol cypionate) resulting in a reduction of the dose of at least 1 of the hormones and results of a study of the efficacy and side effects of these 2 injectables. It hopes the study provides the impetus to introduce them into national family planning programs. It demonstrates that they are indeed efficacious, effect fewer changes in the menstrual cycle than the progesterone only injectables, and are well accepted, even though women must go to a clinic every 27-33 days for an injection. Other studies are determining their effects on lipid and glucose metabolism, coagulation, and fibrinolysis. They are also looking at the time needed for ovulation to return. 1 study shows that menstruation returned in all women by the 3rd cycle.
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PMID:Once-a-month estrogen/progestogen injectables. 1222 32

Injectable progestogen, norethisterone enanthate (NET-EN, 200 mg/ml) was administered to 122 women at 2 month intervals for more than 1 year. Only a minority of women had consistently normal cycles. Most women experienced some menstrual irregularities: 57% of users experienced irregular bleeding, 32% developed amenorrhea, while only 11% showed regular cyclic bleeding. Important nonmenstrual side effects were weakness and abdominal pain. No appreciable changes in body weight and blood pressure were recorded.
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PMID:Clinical trial of a long-acting injectable contraceptive: NET-EN. 1231 44

A prospective study of the use of the injectable contraceptive Norethisterone Oenanthate (NET-OEN) is presented using 96 subjects attending the Family Welfare Centre at the Kenyatta National Hospital, Nairobi, Kenya. 54 subjects had completed 2 years of use and 42 had completed 3 years. 2 pregnancies occured during the study period, giving an incidence of 0.07 per 100 woman months or 0.86 per 100 woman years. Both pregnancies, attributable to method failure, occured after the 5th injection, whereas earlier studies seemed to indicate higher chances of pregnancy within the 3rd month of the 1st injection. There was no marked alteration in body weight and blood pressure. 11% of the subjects with regular cycles at the beginning of the study became amenorrhic at the end of the 3 years. The dropout rate was 56% at 2 years, and 65.7% at 3 years. Thus the continuation rata at 2 and 3 years was 43.9% and 34.3% respectively. 7.2% discontinued for medical reasons, and 35% for social reasons. No patient discontinued use citing amenorrhea as a reason. Bleeding patterns have been analysed and comparisons made with Depo-Provera. This study concludes that NET-OEN is an effective contraceptive agent with relatively few side effects.
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PMID:A 3-year follow-up study of Norethisterone Oenanthate in Nairobi, Kenya. 1231 69

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

Polycystic ovary syndrome (PCOS) is a common heterogenous endocrine disorder associated with amenorrhoea (or oligomenorrhoea), hyperandrogenism, hirsutism, obesity, insulin resistance, and an approximately 7-fold increased risk of type 2 diabetes mellitus (NIDDM - non-insulin dependent diabetes mellitus). It is a leading cause of female infertility. The prevalence of PCOS among reproductive-age women has been estimated at 4%-12%. Familial aggregation of this syndrome is well established. There are also ethnic and racial variations in the prevalence of the syndrome and its symptoms. Multiple biochemical pathways have been implicated in the pathogenesis of PCOS. Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. Most women with PCOS, both obese and lean, have a degree of insulin resistance. The minisatellite of insulin gene (INS VNTR), especially class III alleles and III/III genotypes might not only determine the predisposition to anovulatory PCOS but also the concomitant risk for development of type 2 diabetes. The function of the insulin receptor (IR) is probably normal in woman with PCOS. However abnormal serine phosphorylation in the receptor may impair signal transduction accounting for a post-binding defect in insulin action. Serine phosphorylation is also involved in the postranslational regulation of 17,20-lyase activity (CYP17). There may be a common aetiology for both insulin resistance and hyperandrogenism. Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. PCOS appears to be associated with the absence of the four-repeat-units allele in a polymorphic region of pentanucleotide (TTTTA)n repeats within CYP11A gene, which encodes cytochrome P450scc. It has been hypothesized that up-regulation of this enzyme could lead to increased androgen production. There is no evidence of any association of alleles of CYP19 gene (encoding cytochrome P450arom) with PCOS. Association exists between androgen receptor gene (AR) polymorphisms an androgens action in PCOS. Increased hirustism and decreased CAG repeat length within AR gene has been also demonstrated in women with normal testosterone levels. Expression of estrogen receptor (ERs) as well as 5-alpha-reeducates (SRD5A1-2 genes) activity was analysed in granulosa (GC) and theca cells (TC). The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. On the other hand elevated SRD5A activity in polycystic ovaries supported the hypothesis that 5-alpha-reduced androgens may play a role in the pathogenesis of the syndrome. The genetic aetiology of PCOS remains unknown. There are a number of interlinking factors that affects expression of PCOS. Single cause of PCOS is unlikely. Other possible mechanisms in pathogenesis of PCOS are discussed.
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PMID:[Genetic aspects of polycystic ovary syndrome]. 1635 Jul 21

Gestational trophoblastic disease in perimenopausal women is very rare. A 53-year-old perimenopausal woman complained about amenorrhea lasting over a period of 4months. Ultrasound showed enlargement of the uterus with a complex echogeneous area in the uterine cavity. Serum human chorionic gonadotropin was 67,611mIU/ml. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The uterus contained hemorrhagic and fragile tumor with grape-like vesicles in the enlarged endometrial cavity. Microscopic examination revealed hydropically degenerated villi with circumferential hyperplasia of atypical trophoblast and cistern formation. p57(kip2) immnostaining was negative in villous cytotrophoblasts and stromal cells. Moreover, fluorescent in situ hybridization for HER2 was scored as diploid. These findings are consistent with complete hydatidiform mole. The diagnosis of hydatidiform mole must be considered in perimenopausal women, and the combination of p57(kip2) immunostaining and HER2 fluorescent in situ hybridization seems to be a very useful testing strategy for difficult situations regarding the differential diagnosis of completed and partial hydatidiform mole.
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PMID:A case of complete hydatidiform mole in a perimenopausal woman with diagnostic usefulness of p57(kip2) immunohistochemistry and HER2 fluorescent in situ hybridization. 2219 73

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age. It is characterized by anovulation, oligo- or amenorrhea, hyperandrogenism, obesity, and insulin resistance. PCOS patients present with elevated levels of vascular endothelial growth factor (VEGF) in serum and follicular fluid. In this study, we examined the ovarian expression of angiopoietins (ANGPT) and their receptor tyrosine kinase receptor (TIE2), involved in the stabilization of blood vessels, in a rat model of dehydroepiandrosterone-induced PCOS. We also analyzed the effect of ovarian VEGF inhibition on ANGPT/TIE2, follicular development, and vascular stability. VEGF levels were increased in the PCOS ovaries, whereas the levels of its receptor fetal liver kinase-1 were decreased. In addition, the periendothelial cell area and the ANGPT1 to ANGPT2 ratio in the ovary were increased in the PCOS group. Percentage of primary follicles was increased and the percentage of preantral follicles and corpora lutea was decreased in the PCOS group. VEGF inhibition decreased the percentage of primary follicles close to control values. Interestingly, despite the presence of cysts in the ovaries from VEGF inhibitor-treated PCOS rats, its percentage was lower than the PCOS group without treatment. In summary, this study describes an alteration not only in the VEGF/fetal liver kinase-1 system but also in the ANGPT/TIE2 system in a dehydroepiandrosterone-induced PCOS rat model. This leads to an increase in periendothelial cell recruitment. We also demonstrated that ovarian VEGF inhibition can partially restore the accumulation of small follicles in PCOS rats and reduces cyst formation, improving ovulation and follicular development. Therefore, the inhibition of VEGF could be considered, in addition to other currently applied treatments, as a new strategy to be studied in PCOS patients to restore ovarian function.
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PMID:Angiopoietins/TIE2 system and VEGF are involved in ovarian function in a DHEA rat model of polycystic ovary syndrome. 2257 12

Hydatidiform mole (HM) is rare in postmenopause, with only 7 cases reported. The occurrence of ectopic HM is also rare, with 26 fully documented tubal cases. We are not aware of any reported cases of ectopic HM in a postmenopausal patient. In a 51-year-old patient with 3 years amenorrhea, surgery revealed a necrotic, hemorrhagic mass involving the right peritubal space. Microscopically, chorionic villi were seen within the hemorrhagic mass accompanied by circumferential trophoblast hyperplasia. Immunohistochemically, p57(kip2) positive nuclei were prominent in the extravillous (intermediate) trophoblast. The HER2 FISH expression was diploid, consistent with the diagnosis of an early complete HM.
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PMID:Ectopic Complete Hydatidiform Mole Presenting as an Adnexal Tumor in a Postmenopausal Patient. 2414 Oct 24

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 36-year-old premenopausal woman had been diagnosed with stage III breast cancer. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer, measuring 7 cm. The tumor had lobular histology and was considered grade 2 of 3. Metastatic carcinoma was identified in 10 of 13 axillary nodes. Immunohistochemical studies showed that the tumor was strongly positive for estrogen and progesterone receptor expression and had a Ki-67 score of 15% (> 20% is considered high according to a Swedish quality control study and the St Gallen Expert Consensus).(1,2) There was no amplification of the HER2/neu gene. Staging scans were negative for metastatic disease. In the adjuvant setting, she received three cycles of anthracycline-cyclophosphamide combination chemotherapy followed by three cycles of taxane chemotherapy and then locoregional radiotherapy. After completion of chemotherapy, she developed amenorrhea. As adjuvant endocrine therapy, she began monthly goserelin administration to achieve ovarian function suppression (OFS), in combination with the aromatase inhibitor (AI) exemestane. She experienced menopausal symptoms including hot flashes, vaginal dryness, and sexual dysfunction. After two monthly treatments with goserelin and exemestane, a sensitive assay for serum estradiol was checked and returned at 16 pg/mL (61 pmol/L); postmenopausal range for sensitive assay is less than 15 pg/mL (< 50 pmol/L). The patient has now been referred to our unit to discuss further management.
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PMID:Is Estradiol Monitoring Necessary in Women Receiving Ovarian Suppression for Breast Cancer? 2803 82


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