Evaluation of a combined oestrogen-progestogen injectable contraceptive

A combined injection of 50 mg medroxyprogesterone acetate and 10 mg oestradiol cypionate (Cyclo-Provera; Upjohn) was administered monthly for periods ranging from 1 to 18 months, to 120 Black women of reproductive age. No major side-effects were noted, no pregnancies occurred in the 575 cycles studies, and the pattern of regular menstrual bleeding was acceptable. Amenorrhoea occurred in 15,8% of patients but only 2,5% requested a change of treatment. The incidence of amenorrhoea diminished with continued use. This contraceptive regimen appears to be a useful addition to the methods presently available. Certain aspects merit further study.     

米非司酮、双炔失碳酯及宫内节育器用于紧急避孕临床效果观察

对８４名月经规律的正常妇女在避孕失败或无保护性交后要求紧急避孕者，按本人意愿分为３组：Ａ组（ｎ＝２４）于性交次日开始服米非司酮２５ｍｇ／１２ｈ、２天，共１００ｍｇ；Ｂ组（ｎ＝３０）性交次晨服双炔失碳酯７．５ｍｇ，１２小时后再服７．５ｍｇ，以后每晚服７．５ｍｇ，连服１０天，共９０ｍｇ；Ｃ组（ｎ＝３０）于性交后１２０小时内放置宫内节育器（ＩＵＤ）Ｍｕｌｔｉｌｏａｄ（ＭＩ）Ｃｕ３７５。结果：Ａ及Ｃ组无一例妊娠，成功率１００％，Ｂ组妊娠２例，成功率９３％。主要的副反应是恶心、呕吐等胃肠反应，均在Ｂ组出现，而月经改变以Ｂ及Ｃ组为多见。认为，米非司酮的效果优于双炔失碳酯；ＩＵＤ在排除了生殖道感染的妇女中使用，能取得满意的效果。     

A study of an indigenous drug Maswin as an oral contraceptive

A clinical trial of the oral indigenous contraceptive Maswin was conducted on 48 fertile women (ages 26-42) for 1 year covering 538 menstrual cycles. 1 tablet (400 mg Embelia ribes extract) was taken each morning for 10 days beginning on the fifth day of menstration; total dosage was 10 tablets for 1 menstrual cycle. No pregnancies, side-effects, or toxic symptoms occurred. All expressed a sense of well-being and were eager to continue useage of Maswin. Embelia ribes antagonizes the effects of estrogen on the uterus so the uterus is not in the necessary condition to accept fertilized ovum, so pregnancy does not take place even though ovulation and fertilization have occurred.     

国产皮下埋植剂可接受性的对比研究

自１９９４年４～６月共接收对象１８４６人。课题统一设计，统一表格，经过筛选对象随机植入国产Ｉ或Ｉ型皮下埋植剂，术后按期回访。术后６、１２、２４个月时随访率分别为９７．３５％、９９．１２％及９６．１５％；两型的２年末净累积妊娠率分别为０及０．３６８／每百妇女；同期继续使用率分别为９０．６６及８９．５３／每百妇女。两型药物的有效率及继续使用率均无显著性差异（Ｐ＞０．０５）。术后６、１２、２４个月副反应发生率，Ｉ型为６２．３％、３２．８５％、２３．９３％；Ｉ型为６３．６９％、３２．１１％、２２．７１％（Ｐ＞０．０５）。其中以月经异常最常见（占４０％以上），其他依次为类早孕反应、情绪改变等。月经异常经Ｌｏｇｉｓｔｉｃ多元回归分析，年龄越小、孕次越少、文化程度越高，月经异常发生率越高。术后体重、血压、乳房及盆腔等项检查均未发现明显异常。认为国产（Ｉ型、Ｉ型）皮下埋植剂具有长效、高效及可接受性好等优点，可推广使用     

每周口服25mg米非司酮避孕的多中心临床研究

目的探讨25mg米非司酮用于常规避孕的可行性。方法在全国7个研究中心选择自愿参加的健康妇女,受试者月经周期第2~3天首次服用1片(25mg)米非司酮,以后每周服药1次,每次1片,共服4次。每4周随访一次,以28d为一个研究周期,持续6个周期。观察其避孕效果、对月经的影响以及副反应。结果研究在全国7家研究所/医院进行,共接收504名受试者。在完成随访的502名妇女,共3 006个研究周期中,有3例妊娠,其中2例未按照要求服药。与服药前周期相比,服药第4、5、6周期出血天数减少、无出血天数增加,且无出血妇女占比增加,均有统计学差异(P0.05)。恶心、乳胀等副反应较少见且轻微。结论每周一次口服25mg米非司酮避孕效果好,胃肠道等副反应轻微。但随着服药时间的延长,米非司酮会对妇女的月经模式产生比较显著的影响。     

上海市两社区初婚已分娩夫妇人工流产后开始选用避孕措施状态及影响因素的分析

对上海市两社区 71 0 1对于 1 987～ 1 988年初婚并于婚后 5～ 6年时已有孩子的夫妇进行 8年的前瞻性队列调查。结果显示 ,其中 9.3 % (6 6 3对 )的夫妇是于人工流产(人流 )术后开始选用避孕措施 (在本次调查的 2 52 7例产后至少有一次人流者中占2 6 .2 % )。在 6 3 3例产后完全暴露于妊娠危险状况的夫妇中 ,1 / 3的妻子因感避孕麻烦而原就准备于人流术后放环避孕。 51 .3 %的夫妇认为产后夫妇性生活少、哺乳期或未转经、月经量少不会受孕等而未于产后及时避孕。近 80 %未及时避孕的妻子于恢复性生活后 1年内受孕。56 .4 %未及时避孕的妻子均于人流术后放置环 ,其中 1 / 2的妻子认为于该时放环最有效。在产后非人流术后开始避孕的妻子中仅 8.1 %首选放环 ,从有效性出发首选放环的仅占 1 / 3。拟合双反应 L ogistic回归模型显示夫妇人口统计学 (妻子婚龄、宗教信仰、夫妇月收入 ) ,生育意愿 (婚后推迟生育时期 ) ,心理学因素 (产后妻子健康状况 ) ,妻子对人流的态度 ,夫妇的避孕知识 (特别丈夫在二访时 ) ,性生活状况等多种因素均显著影响到夫妇产后是否及时避孕。结果显示 :(1 )要加强对夫妇 ,特别是妻子 ,产后一旦恢复性生活及时避孕的教育 ;(2 )对有关人流后放环和人流术本身对妇女健康潜在危险性等开     

Timing of surgery with regard to the menstrual cycle in women with primary breast cancer

There is sufficient evidence to support both the hormonal influence on the outcome of breast cancer surgery and the SDA hypothesis. The SDA model produces a paradigm shift in the understanding of the natural history of breast cancer. It offers opportunities to try modifying a tumor's biological potential for metastasis (e.g., by tamoxifen, progesterone, antiprotease, or angiostatin) in the neoadjuvant setting. It continues to support the beneficial effects of detection and surgery early in the natural history of disease. It would be worthwhile to plan a trial comparing standard practice (unplanned surgery as the patient enrolls) with surgery during the luteal phase of the menstrual cycle in premenopausal women. Another possibility, based on studies of circulating progesterone, would be to compare primary progesterone treatment (for 4 to 10 days before surgery) with standard practice. Such a trial of primary progesterone is already under way, conducted by the Indian Breast Group. More than 200 patients have enrolled so far. The details of the trial are available from Clinical Research Secretariat, Tata Memorial Centre, Parel, Mumbai, India (e mail: tmho3@bom2.vsnl.in).     

Menstruation, the oral contraceptive pill, and acute appendicitis.

OBJECTIVE: To find out if there was any association between histologically confirmed acute appendicitis, menstruation, and the use of the oral contraceptive pill. DESIGN: Retrospective study. SETTING: District general hospital, Scotland. SUBJECTS: 366 consecutive patients (median age 21, range 10-51) with histologically confirmed acute appendicitis during the period 1981-1990 were studied, 314 of whom were having menstrual cycles. 208 patients with physiological menstrual cycle were included in the study, and 82 patients were taking the oral contraceptive pill. INTERVENTIONS: Prospectively collected standardised data using computer assisted diagnosis of acute abdominal pain was used to review patients with histologically confirmed acute appendicitis. RESULTS: Acute appendicitis was confirmed in 17/208 of patients (8%) who were menstruating, which is significantly less than might be expected (p < 0.003). 5/82 (6%) of those taking oral contraception had withdrawal bleeding and acute appendicitis (p = 0.2). CONCLUSIONS: Acute appendicitis is less common among women during physiological menstruation, but no differences are noted during the withdrawal bleeding phase when taking oral contraception.     

Effect of oral contraceptive containing a new progestin (ORG 2969) on plasma renin activity, growth hormone and immunoreactive insulin.

Plasma renin activity (PRA), Growth hormone (GH) and immunoreactive insulin (IRI) were studied in seven healthy subjects during the ovulatory menstrual cycle and during the first and third cycles of oral contraception with 0.05 mg of ethinylestradiol and 0.100 mg or 0.125 mg of a new progestogen, 17 alpha-ethinyl-18-methylene-4-estren-17 beta-ol. The PRA level in the second half of the control cycle was significantly higher than in the beginning of the cycle. At the end of the treated cycles it was significantly higher than at the end of the control cycle. Neither GH nor IRI showed significant changes during the control cycle. GH was significantly higher at the end of the first and third treated cycles than at the end of the control cycle. IRI was significantly higher both in the beginning and at the end of the first treated cycle than the corresponding IRI levels in the control cycle. IRI at the end of the third treatment cycle was not significantly different from corresponding means at the end of the control cycle or the first treated cycle.     

孕三烯酮用于紧急避孕120例临床观察

目的 :对孕三烯酮 ( R2 3 2 3 )的紧急避孕效果、副反应及对下次月经的影响进行前瞻性临床观察。方法 :1 2 0名要求紧急避孕的妇女 ,单次口服 5mg R2 3 2 3后进行随访 ,观察用药后的副反应和月经情况 ,按 Dixon法推算其避孕有效率。结果 :1 2 0名受试者的总预期妊娠数为 9.0 1 4,实际妊娠 1例 ,避孕有效率为 88.9% ,失败率为 0 .83 %。 1 0 %的受试妇女有轻微头痛、腹痛、恶心、呕吐等副反应 ,无需特殊处理。对下次月经无明显影响。结论 :5mg R2 3 2 3用于紧急避孕时安全有效 ,剂量小 ,副反应少 ,对月经周期无明显干扰。尚有待于大样本多中心研究证实     

药铜宫内节育器的恒河猴实验研究

实验选用恒河猴放置药铜宫内节育器（ＬＮＧ－Ｃｕ－ＩＵＤ：ＬＮＧ６μｇ／ｄ，Ｃｕ２００ｍｍ２）６个月，以观察其节育效果及月经情况。结果：节育效果好，无妊娠、无脱落；月经改变表现为出血不规则、经量减少及闭经，但取器后即恢复正常；宫腔冲洗液ＰＧｓ放免测定，置器前后ＰＧＥ２、ＰＧＦ２α、６－ｋｅｔｏ－ＰＧＦ１α浓度无显著差异，ＴＸＢ２明显上升，６－ｋｅｔｏ－ＰＧＦ１α／ＴＸＢ２比值下降，提示ＬＮＧ－Ｃｕ－ＩＵＤ导致周期出血减少可能与此有关；置器后子宫内膜上皮细胞和若干酶活性不同程度受抑。结果提示：兼释ＬＮＧ和Ｃｕ２＋的ＩＵＤ具有节育效果可靠、经血量少等优点，但对月经的影响尚需深入研究。     

Treatment of menstrual disorders with a combination of norgestrel and ethynyl estradiol

In order to determine the efficacy of oral contraceptives in the treatment of menstrual dysfunction, 44 patients complaining of menstrual disorders were treated with a norgestrel--ethinyl estradiol combination oral preparation (Ovral) at the Vani Vilas Hospital in India in 1969-70. The patients' major complaints included spasmodic dysmenorrhea, dysfunctional uterine bleeding, and menorrhagia with varying indications of fertility and diagnostic confirmation of dysfunction. Those patients who were bleeding heavily at the time of examination were administered 1 tablet of 0.5 mg norgestrel and 0.05 mg ethinyl estradiol 3-4 times daily until the bleeding stopped and then maintained on 1 daily dose along with the other patients with less serious bleeding episodes until Day 21 of treatment. The first day of withdrawal bleeding after cessation of the first treatment was counted as Day 1 and cyclic treatment of 1 tablet daily for 3 weeks and 1 week off was started on Day 5. All 14 patients reporting spasmodic dysmenorrhea had complete relief of symptoms and 1 case of primary infertility conceived after the therapy. Similar results were obtained in the dysfunctional uterine bleeding group. Endometrial biopsies in the metropathic and menorr,agic patients revealed a return to normal endometrial function. The drug was extremely well tolerated in all patients with only 2 patients reporting minimum side-effects. It is concluded that oral contraceptive preparations are highly effective in the therapeutic manipulation of menstrual function.     

The Contraceptive Vaginal Ring in Women With Renal and Liver Transplantation: Analysis of Preliminary Results

Introduction

Vaginal administration seems to be the best route to achieve steady and precise doses of contraceptive hormones, resulting in stable serum concentrations and low exposure. The aim of this study was to evaluate the contraceptive efficacy, cycle control, tolerability and acceptability of a contraceptive vaginal ring (NuvaRing) in renal and liver transplant recipients.

Material and Methods

Renal or liver transplant recipients, asking for contraception, were enrolled into the study. The duration of treatment was 12 cycles, with each vaginal ring releasing an average of 120 mg etonogestrel and 15 mg ethinylestradiol daily. Study visits were scheduled at screening, in the first week following cycles 3, 6, and 12 (172 cycles).

Results

Among 17 females included into the study: were 9 renal (mean age, 30 ± 7.2 years) and 8 liver transplant recipients (mean age, 32.6 ± 6.6 years). At the onset of therapy all patients showed at least 6 months of stable graft function with no signs of allograft rejection. The mean posttransplant follow-up was 4 ± 3.6 and 5.3 ± 2.1 years for women with renal and hepatic transplantations respectively (P = NS). The immunosuppressive therapy was not changed for any patient. We demonstrated good cycle control: 162 cycles did not exhibit any bleeding; 7 cycles, only spotting episodes, whereas 2 cycles had 1 bleeding episode during the ring period. The estrogen-related adverse events (nausea and breast tenderness) were reported in 2 patients. One patient experienced significant bleeding related to thrombocytopenia.

Discussion

Nuvaring, in our preliminary findings, may be considered to be an highly effective contraceptive method for female transplant recipients that additionally regulate menstrual bleeding and seems to positively influence well-being. Vaginal administration may diminish the chance of drug interactions and therefore be safer for patients.     

Sexual and Reproductive Health Assessment in a Group of Female Renal Transplant Recipients

BackgroundFertility and sexual health are impaired in individuals with chronic kidney disease and can be restored after a successful renal transplant. This is a single-center prospective study about the sexual and reproductive health (including contraceptive methods and gynecologic cancer screening) in renal transplant recipients.MethodsFemale renal transplant recipients, aged 18 to 49 years at transplant, were interviewed about their gynecologic history, sexual health, and use of contraceptive methods.ResultsNinety-one patients fulfilled the inclusion criteria. The majority of women maintained menstrual cycles during dialysis therapy, being almost 60% of the women in an irregular rhythm. Pregnancies were reported for 51 women, 20% after transplant, and associated with low-weight newborns. The incidence of spontaneous abortion was 12.5%. Thirty-one patients were denied contraceptive methods due to the vasectomy of the partner (n = 16) or the belief that they would not become pregnant (n = 15). The most common contraceptive method was a condom, and the use of an intrauterine device was rare. Gynecologic assessment and cancer screening were out-of-date in almost one-third of patients.ConclusionsIn this study, the majority of women were from low-income areas and had low levels of education. Despite access to public universal health care, adherence to yearly screening tests and use of contraceptive methods were lower than expected.     

含消炎痛铜宫形器临床效果初步观察

随机比较了含消炎痛铜宫腔形节育器（药铜器）和对照组含铜宫腔形节育器（宫铜器）各２０５例，观察一年的临床效果。结果显示，两组妊娠率、脱落率、因出血／疼痛取出率、续用率分别为：０．４９和１．５０、１．４９和１．９８、０．９９和２．００、９７．０４和９４．６１／１００妇女；两组比较差异均无显著意义（Ｐ均＞０．０５）。置器后３个月时，宫铜器组副反应发生多于药铜器组；月经血量减少药铜器组明显多于宫铜器组（Ｐ＜０．０１），而点滴出血药铜器组明显少于宫铜器组（Ｐ＜０．０５）。两组各测定１５例置器前后的月经血量，药铜器组置器后较置器前不增加或减少７％～１３％，而宫铜器组置器后增加２３％～２７％。提示药铜器能减少置器后早期出血副反应的发生。     

Oral and transdermal hormonal contraception in women after kidney transplantation

AIM: The aim of the study was to assess the safety of low-dose oral or transdermal hormonal contraception in kidney recipients. MATERIALS AND METHODS: Twenty-six kidney recipients, aged 18 to 44 years (mean, 31.0) took low-dose contraceptive pills, and 10 kidney recipients, aged 22 to 36 years (mean, 31.4) used transdermal contraceptive systems. Contraception was administered for a period not shorter than 18 months. At the onset of therapy all patients showed stable graft function. The main indication for therapy was effective contraception. Additional indications were mild ovarian cysts and irregular or profuse menstruations. The pills consisted of 20 to 35 microg of etinyl estradiol and generation III progestogen. The contraceptive patch released 20 microg of etinyl estradiol and 150 microg of norelgesromin daily. RESULTS: No case of pregnancy was noted. Oral contraception was discontinued in two cases, in one case due to profound thrombophlebitis of the lower extremity and in the other case deterioration of liver function. No other side effects or symptoms of intolerance were reported. Hormonal contraception did not significantly influence body mass index, mean blood pressure, serum creatinine, or other biochemical parameters. CONCLUSION: Despite the presence of relative contraindications, mainly arterial hypertension and impaired liver function, hormonal contraception should be considered in female kidney recipients to be a highly effective contraceptive method that additionally regulates menstrual bleeding, protects from development of mild ovarian cysts and seems to positively influence women's well-being. The transdermal mode of administration may diminish the chance for drug interactions and therefore be safer for patients.     

Effect of combined oral contraceptives on breast epithelial proliferation in young women

The mammary gland undergoes morphologic changes during the menstrual cycle. Proliferation of normal breast epithelium is most extensive during the natural luteal phase. To determine the impact of one cycle of a combined oral contraceptive (COC) on breast homeostasis, we evaluated the proliferation index (PI), determined by KI-67 expression, in normal human mammary epithelial cells and correlated it with cellular proliferation in spontaneous menstrual cycles during the same period. Normal breast tissue samples were obtained from 82 patients randomized in two groups. Forty-two women in group A received one cycle of a COC (30 mug ethinyl estradiol and 150 mug levonorgestrel) administrated daily for 21 days, beginning on the first day of the menstrual cycle. Group B patients (n = 40) experienced a natural menstrual cycle. Menstrual cycle phase characterization was based on the date of the last period and subsequent menses and on progesterone serum levels obtained at the time of biopsy. The PI (number of Ki-67-positive nuclei per 1,000 epithelial cells), was significantly larger in group A (5.47 +/- 3.87), than in group B (3.27 +/- 3.24), p < 0.01. A cyclical variation of PI was observed in COC cycles. The rise in PI in the first week of the COC cycles was significantly higher than in the natural cycle (COC = 7.02 +/- 4.94; non-COC = 1.10 +/- 0.67; p < 0.0011). There was no significant difference between the two groups during the other weeks. Additionally, there was an inverse correlation between proliferation and chronological age, irrespective of the stage of the cycle. The PI of COC (p = 0.175) and natural cycles (p = 0.466) were not statistically different in younger patients. COC users have increased proliferative activity at the beginning of the menstrual cycle. This alteration in the pattern of proliferative activity may relate to the increased risk of breast cancer that has been associated with COCs.     

Changes in bone resorption during the menstrual cycle.

To determine if the cyclic changes of female sex hormones during the menstrual cycle are related to changes in bone formation and resorption, we measured serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) and bone resorption markers, serum and urine deoxypyridinoline (Dpyr), three times per week during one menstrual cycle in 20 healthy premenopausal women. Serum estradiol (E2) and progesterone (P) showed characteristic cyclic fluctuations. Serum Dpyr was higher during the follicular phase (FP) than in the luteal phase (p = 0.027). Serum BAP, OC, and urine Dpyr levels did not change substantially across the cycle. Serum Dpyr correlated negatively with serum E2 values measured 6 (p = 0.011) and 8 (p = 0.001) days earlier and with P measured concurrently (p = 0.033) 2 (p = 0.002), 4 (p = 0.003), and 6 (p = 0.014) days earlier. BAP correlated negatively with E2 measured 6 days earlier (p = 0.006). We found no statistically significant correlations of E2 or P with OC or urine Dpyr within women over their cycles. BAP was positively correlated with concurrent serum Dpyr (p = 0.015) during the menstrual cycle. Serum OC levels correlated inversely with age (rs = -0.48, p = 0.036). Women with higher mean urine Dpyr levels had higher mean serum OC levels (rs = 0.49, p = 0.033) and showed a trend toward lower hip bone mineral density (rs = -0.40, p = 0.078). We conclude that the low level of E2 and/or P observed during the FP of the normal menstrual cycle is associated with increased bone resorption. These relationships suggest that normal women experience monthly episodes of increased bone resorption from menarche to menopause.     

Effects of oral contraceptive and estrogen administration on plasma calcitonin in pre- and postmenopausal women

Estrogen (E) therapy and administration of oral contraceptives (OC) reportedly increase plasma calcitonin (CT) concentrations in women, effects said to mediate in part the beneficial actions of E on bone. To further examine this theory, we tested the effects of three cycles of OC therapy in 12 young women, comparing them to 10 healthy women before and after three normal menstrual cycles. We also determined the effects of 3 months of E therapy (ethinyl estradiol, 20 micrograms/day, 25 of 30 days) in 14 healthy postmenopausal women, using a crossover design (studied after 3 months with and 3 months without E). We determined CT by radioimmunoassay (antiserum G-1701) in whole plasma (iCT) and silica cartridge extracts of plasma (exCT) after overnight fasting, after calcium (Ca) infusion (2 mg Ca/kg over 5 minutes), and during a normal day at 0800, 1200, 1700, and 2000 h. In no control study was there a significant diurnal change in iCT or exCT, and neither OC nor E therapy altered this. Similarly, OC administration did not affect basal CT levels or the normal iCT and exCT responses to Ca infusion. E therapy induced expected changes in serum Ca, phosphorus, and alkaline phosphatase and urinary Ca and cAMP excretion; basal and diurnal plasma exCT levels were decreased significantly, consonant with the decrement in serum Ca. E did not alter normal iCT and exCT responses to Ca infusion. Thus, administration of either OC or E has no stimulatory effect on CT secretion, which suggests that the beneficial actions of E on bone are not mediated through CT-induced inhibition of bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of oral contraceptive use on the renal and systemic vascular response to angiotensin II infusion

We have previously shown that users of oral contraceptive (OC) medications exhibit increased plasma levels of angiotensin II (Ang II) with only modest hemodynamic consequences, suggesting estrogen-mediated Ang II type 1 (AT(1)) receptor downregulation. Accordingly, in 10 women who were OC users and 10 women who, as OC nonusers, served as controls, all mean age 26 +/- 1 yr, we examined the renal and peripheral hemodynamic response to graded Ang II infusion, plasma and urine cyclic guanosine monophosphate (cGMP) levels as a surrogate marker for AT(1) and/or AT(2) receptor-mediated activation of the nitric oxide pathway, and AT(1) receptor expression in skin biopsies. The OC nonusers were studied during the follicular and luteal phases of the menstrual cycle, whereas OC users were studied once during the 21-d medication phase. Subjects ingested a controlled sodium diet for 7 d before each study. Renal hemodynamic function was assessed using standard inulin and p-aminohippurate clearance techniques. AT(1) receptor mRNA levels in skin biopsy samples were assessed using a real-time PCR protocol. In response to graded Ang II infusion, OC users exhibited renal and peripheral hemodynamic responses that were augmented compared with those of OC nonusers, in conjunction with evidence of increased tissue AT(1) receptor expression. Plasma cGMP levels and 24-h urinary cGMP excretion did not differ. These data suggest that, contrary to our original hypothesis, OC use does not appear to be associated with AT(1) receptor downregulation. The factor protecting OC users from the hemodynamic impact of increased Ang II levels remains elusive.