Health benefits of oral contraceptives

A sizeable literature corroborates the multiple health benefits of oral contraceptive use. The first estrogen/progestin combination pills were marketed to treat a variety of menstrual disorders. Although currently used oral contraceptives no longer carry FDA-approved labeling for these indications, they remain important therapeutic options for a variety of gynecologic conditions. Well-established gynecologic benefits include a reduction in dysmenorrhea and menorrhagia, iron-deficiency anemia, ectopic pregnancy, and PID. Although older, higher-dose pills reduced the incidence of ovarian cysts, low-dose pills suppress follicular activity less consistently. Nevertheless, cycle-related symptoms, including functional cysts, dysmenorrhea, chronic pelvic pain, and ovulation pain (mittelschmerz), generally improve. Women with polycystic ovary syndrome note improvement in bleeding patterns and a reduction in acne and hirsutism. Symptoms from endometriosis also improve with oral contraceptive therapy. Current data suggest that oral contraceptive therapy increases bone density and that past use decreases fracture risk. Oral contraceptives also improve acne, a major health concern of young women. Oral contraceptives provide lasting reduction in the risk of two serious gynecologic malignancies--ovarian and endometrial cancer. The data with respect to ovarian cancer are compelling enough to recommend the use of oral contraceptives to women at high risk by virtue of family history, positive carrier status of the BRCA mutations, or nulliparity, even if contraception is not required. Health care providers must counsel women regarding these benefits to counteract deeply held public attitudes and misconceptions regarding oral contraceptive use. Messages should focus on topics of interest to particular groups of women. The fact that oral contraceptives increase bone mineral density and reduce ovarian cancer is of great interest to women in their forties and helps influence use and compliance in this group. In contrast, the beneficial effects of oral contraceptives on acne resonates with younger women. Getting the good news out about the benefits of oral contraceptives will enable more women to take advantage of their positive health effects.     

Ovulation induction

In the woman with anovulation and polycystic ovarian syndrome, there are many options for ovulation induction. Treatment should be individualized, but clomiphene citrate is an excellent first-line agent. In the woman resistant to clomiphene citrate, combination therapy often results in pregnancy. Some women with PCOS only respond to gonadotropin therapy. These women are at a higher risk for multiple pregnancy and ovarian hyperstimulation syndrome. In the woman with anovulation and hypothalamic amenorrhea, the options for ovulation induction are limited. The luteal phase must be supported. The hypothalamus is unable to support the corpus luteum or early pregnancy.     

Hormonale Kontrazeption in der Perimenopause

Perimenopause marks the transition from normal ovulation to anovulation. However, perimenopausal women may still be at risk for unintended pregnancy. Various contraceptive methods may be offered including oral contraceptives (OC), tubal ligation, intrauterine devices, barrier methods, hormonal injectables and implants. Furthermore, the contraceptive vaginal ring and the transdermal contraceptive system have been introduced recently. However, these new options have to be further investigated in perimenopausal women. Women should be informed that OC use until menopause or the mid-50s is both safe for healthy, non-smoking women and effective in easing perimenopausal symptoms. OC use during perimenopause can also help reduce risks of bone density loss, as well as endometrial, ovarian and colorectal cancer later in life.     

PCOS: diagnosis and management of related infertility

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is characterised by a combination of hyperandrogenism (either clinical or biochemical), chronic oligo/anovulation, and polycystic ovaries. It is frequently associated with insulin resistance and obesity. PCOS receives considerable attention because of its high prevalence and possible reproductive, metabolic, and cardiovascular consequences. It is the most common cause of anovulatory infertility. Ovulation induction with an aromatase inhibitor or anti-oestrogen is the first-line medical treatment. The aim of ovulation induction is monofollicular growth to avoid multiple pregnancy. The second-line treatments include gonadotrophins and laparoscopic ovarian drilling. The role and benefit of metformin in ovulation induction is uncertain. Woman with PCOS undergoing IVF are at significant risk of ovarian hyperstimulation syndrome. Women with PCOS are also at an increased risk of developing gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia.     

Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies

Ovarian cancer is the leading cause of mortality related to gynecologic malignancies in Sweden but there is no current screening program. Based upon epidemiological research there is evidence that certain reproductive factors are associated with ovarian cancer risk. Most studies generally indicate that each childbirth incurs a 15-20% risk reduction. Women who have used oral contraceptives for 5 years or longer experience about half the risk of ovarian cancer compared with never users. Breastfeeding seems to be protective while age at menarche and at menopause are less consistent risk predictors. Tubal ligation and hysterectomy seem to reduce ovarian cancer risk by up to 80%. Although some studies found endometriosis, polycystic ovarian syndrome (PCOS) and pelvic inflammatory disease (PID) to be positively related to ovarian cancer, the role of these factors is not yet established. Most recent studies observed an approximately 50% ovarian cancer risk increase among ever users of hormone replacement therapy (HRT) compared with never users, and the risk increased further with long-term use. There is less information concerning separate estrogen and progestin effects of HRT and ovarian cancer risk. Although the cause of ovarian cancer remains obscure, hypotheses relating to "incessant" ovulation, excessive gonadotropin secretion, retrograde carcinogen transportation, apoptosis and estrogen/progestin imbalance have been invoked as etiological explanations. All these hypotheses find various epidemiological support. The aim of this review is to summarize the epidemiological findings on reproductive factors and ovarian cancer risk. These findings are considered in the context of etiologic hypotheses and some new research areas are suggested.     

Type 2 diabetes and polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) have multiple factors that contribute to increased diabetes risk, including: insulin resistance, beta-cell dysfunction, obesity, especially centripetal obesity, family history of type 2 diabetes, and personal history of gestational diabetes. Additionally there is some evidence to suggest that polycystic ovaries and chronic anovulation per se are risk factors. Identifying glucose intolerance and treating it are important aspects of the care for women with PCOS.     

Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis

OBJECTIVE: Women with endometriosis may be at an increased risk of ovarian cancer. It is not known whether reproductive factors that reduce the risk of ovarian cancer in general also reduce risk in women with endometriosis. We investigated whether the odds ratios for ovarian cancer that were associated with oral contraceptive use, childbearing, hysterectomy, and tubal ligation differ among women with and without endometriosis. STUDY DESIGN: We pooled information on the self-reported history of endometriosis from 4 population-based case-controlled studies of incident epithelial ovarian cancer, comprising 2098 cases and 2953 control subjects. We obtained data on oral contraceptive use, childbearing, breastfeeding, gynecologic surgical procedures, and other reproductive factors on each woman. Multivariable unconditional logistic regression was used to calculate odds ratios and 95% CI for ovarian cancer among women with endometriosis compared with women without endometriosis. Similar methods were used to assess the frequencies of risk factors among women with and without endometriosis. Adjustments were made for age, parity, oral contraceptive use, tubal ligation, family history of ovarian cancer, and study site. RESULTS: Women with endometriosis were at an increased risk of ovarian cancer (odds ratio, 1.32; 95% CI, 1.06-1.65). Using oral contraceptives, bearing children, and having a tubal ligation or hysterectomy were associated with a similar reduction in the odds ratios for ovarian cancer among women with and without endometriosis. In particular, the use of oral contraceptives for >10 years was associated with a substantial reduction in risk among women with endometriosis (odds ratio, 0.21; 95% CI, 0.08-0.58). CONCLUSION: Women with endometriosis are at an increased risk of epithelial ovarian cancer. Long-term oral contraceptive use may provide substantial protection against the disease in this high-risk population.     

Optimizing ovulation induction in women with polycystic ovary syndrome

Recent developments in our understanding of the pathophysiology of polycystic ovary syndrome led to the introduction of new therapeutic approaches. It is apparent that a significant proportion of women with polycystic ovary syndrome have insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide rationale for therapies focused on treatments of insulin resistance. In particular, weight loss and exercise have been shown to increase insulin sensitivity and improve ovulatory function. Metformin, an insulin-sensitizing agent, is particularly effective in women with polycystic ovary syndrome who have significant insulin resistance. Metformin use leads to a decrease in serum insulin and androgen levels as well as an improvement in ovulatory function. Moreover, it appears to ameliorate cardiovascular risk factors. Other approaches to ovulation induction in women with polycystic ovary syndrome include traditional therapies using clomiphene citrate or gonadotropins. In clomiphene-resistant subjects, one can consider laparoscopic ovarian drilling and other forms of partial ovarian resection or destruction.     

林奇综合征患者子宫内膜癌及卵巢癌的筛查与预防

患有林奇综合征(Lynch syndrome,LS)的妇女终生患子宫内膜癌和卵巢癌风险大幅增加.而子宫内膜癌或卵巢癌可以是LS患者的首发恶性肿瘤,也可以是第二原发恶性肿瘤.LS相关子宫内膜癌主要类型是子宫内膜样腺癌.近年来,有关LS相关子宫内膜癌及卵巢癌的筛查研究较少,主要是通过门诊子宫内膜活检、微卫星高不稳定性(mi...     

Polycystic ovarian syndrome--prognosis and treatment outcomes

PURPOSE OF REVIEW: Polycystic ovarian syndrome is the commonest endocrine disorder of reproductive-age women. It may have implications for women with regard to anovulatory infertility, insulin resistance and elevated androgens. Furthermore, patients are prone to health problems in later life, including diabetes and cardiovascular risk. This review provides an update of recent findings for the management of polycystic ovarian syndrome. RECENT FINDINGS: Studies have been performed to determine the best first-line medication for ovulation induction in polycystic ovarian syndrome. Meta-analyses have been performed to determine whether metformin should be used as an adjunct in IVF in women with this syndrome and to determine whether metformin or the oral contraceptive pill should be used for symptom control. Adverse features of this syndrome can be improved by diet and exercise. Evidence for the longer-term use of metformin to protect against adverse cardiovascular outcomes, and for its pregnancy use to reduce gestational diabetes, preeclampsia, and fetal macrosomia is lacking, although evidence for a reduction in miscarriage in insulin-resistant patients is accumulating. SUMMARY: Recent studies have sought to clarify the serious short-term clinical problems faced by women with polycystic ovarian syndrome; however, studies looking to the long term to address cardiovascular and diabetic conversion are still required.     

A case-control study of epithelial ovarian cancer

With data from a study of 296 patients with primary epithelial ovarian cancer and 343 patients hospitalized because of other conditions, we estimated ovarian cancer risk in accordance with reproductive and other factors. Risk was greatest among women of lower parity, especially among women who said they planned to have children but could not. The protective effect of oral contraceptives seen in other studies was observed only in subgroups of our study population. Women who had breastfed their children had decreased risk, but the number of months of breastfeeding was not related to risk. Incomplete pregnancies did not provide the protection seen for live births. A family history of ovarian cancer and a medical history of breast cancer were both strong risk factors. None of the nonreproductive factors that we examined, including childhood illnesses, tobacco and alcohol consumption, obesity, and selected adult diseases, was convincingly associated with risk.     

The pathogenesis of infertility and early pregnancy loss in polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) frequently present with reproductive dysfunction. Ovarian function might be disturbed, with resultant abnormal folliculogenesis and steroidogenesis and, although it is difficult to define the exact pathogenesis of anovulation, many possible mechanisms have been postulated. Folliculogenesis in anovulatory women with PCOS is characterized by failure of dominance and the ovary has multiple small follicles, which are arrested but capable of steroidogenesis. Abnormalities in gonadotrophin and insulin secretion and disordered paracrine function have been identified. Women with PCOS have an increased prevalence of miscarriage, both after spontaneous and induced ovulation. Hypersecretion of LH, hyperandrogenaemia and hyperinsulinaemia have all been investigated as possible causes of PCOS. It is likely that these factors are interlinked and together might result in disordered ovarian and endometrial function. Multiple other possible abnormalities have been postulated as contributory factors in the reproductive failure. These include decreased plasminogen activator inhibitor activity, endothelial dysfunction and obesity. Ideally, therapy should target the underlying disorders but at present data are inadequate and further investigations are essential before therapeutic recommendations are truly based on an understanding of the pathophysiology.     

Therapeutic options in the polycystic ovary syndrome.

The polycystic ovary syndrome is the most common endocrine disorder affecting women. It is a heterogeneous familial condition of uncertain aetiology. The diagnosis is made by the detection of polycystic ovaries on ultrasound examination and the occurrence of single or multiple clinical features such as menstrual cycle disturbances, obesity, acne, hirsutism, alopecia and biochemical abnormalities such as hypersecretion of luteinising hormone and testosterone. In a significant number of women with this condition there is impaired insulin metabolism. Women with the polycystic ovary syndrome are at an increased risk of developing diabetes and possibly cardiovascular disease in later life. The management should be symptom-orientated. Menstrual cycle regulation may be attained with the combined oral contraceptive pill or cyclical progestogen therapy. In obese women, with the loss of weight, the symptoms and endocrine profile are generally improved. Short-term treatment with metformin may be useful in women with insulin resistance. Hyperandrogenism may be treated with the contraceptive pill containing cyproterone acetate or with short-term low-dose anti-androgen therapy, together with effective contraception. Ovulation may be induced with clomiphene citrate with careful monitoring, failing which low-dose gonadotrophin therapy or laparoscopic ovarian diathermy are effective options.     

Induction of ovulation in infertile women with hyperandrogenism and insulin resistance

The polycystic ovary syndrome is a common cause of anovulatory infertility. Women with severe insulin resistance are a unique subset of polycystic ovary syndrome. The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) is one presentation of the insulin-resistant subset of polycystic ovary syndrome. Insulin resistance and hyperandrogenism are caused by genetic and environmental factors. In women with anovulatory infertility caused by hyperandrogenism and insulin resistance, clomiphene citrate treatment often fails to result in pregnancy. For these women, weight loss and insulin sensitizers can be effective methods of inducing ovulation and pregnancy and may reduce the number of clomiphene-resistant women with polycystic ovary syndrome who are treated with gonadotropins, ovarian surgery, or in vitro fertilization-embryo transfer.     

Polycystic ovarian syndrome: diagnosis and management of related infertility

Polycystic ovarian syndrome (PCOS) is a common gynaecological endocrinopathy seen in women of reproductive age, characterized by a combination of hyperandrogenism (either clinical or biochemical), chronic oligo/anovulation, and polycystic morphology of ovaries. It is a disease with metabolic, reproductive, and psychological impacts. It is the most common cause of anovulatory infertility. Lifestyle modifications including dietary modifications and exercise are the first line therapy, effectively improving the metabolic and endocrine milieu, and ovulation which ultimately improves pregnancy rate. Ovulation induction with aromatase inhibitor (letrozole) or anti-estrogen (Clomiphene citrate) is the first option as regards medical treatment. The aim of ovulation induction is mono-follicular growth to avoid multiple pregnancies. Gonadotropins and laparoscopic ovarian drilling form the second line of treatment. In vitro Fertilization (IVF) is positioned as third-line management option for PCOS in absence of associated factors demanding IVF, but is associated with significant risk of ovarian hyperstimulation syndrome (OHSS). GnRH antagonist protocol with GnRH agonist trigger for final oocyte maturation and freeze-all policy helps to eliminate OHSS risk up to a large extent. Pregnancy with any form of therapy is at an increased risk of developing gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia, which needs to be counselled to patients while treating PCOS related infertility.     

An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin therapy for women with clomiphene citrate-resistant polycystic ovarian syndrome

PURPOSE OF REVIEW: Women with polycystic ovarian syndrome are typically anovulatory and require ovulation induction. Ovarian wedge resection was the first treatment for anovulation but was eventually abandoned because of the increased risk of postsurgical adhesions and as medical ovulation induction with clomiphene and gonadotrophins was introduced. However, with the advent of laparoscopy, there has been a return to surgical approaches. The potential advantages of laparoscopic surgery include avoidance of hyperstimulation and the lowered costs make ovarian surgery an attractive alternative to gonadotrophins. RECENT FINDINGS: Clinical trials in New Zealand and the Netherlands have compared costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of treatment in the Netherlands study for the ovarian drilling group was euro 4664 and for the gonadotrophins group was euro 5418. Without the cost of monitoring and the diagnostic laparoscopy then the difference was euro 2110 in favour of ovarian drilling. It was estimated that the cost per term pregnancy would be euro 14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The higher rates of multiple pregnancy in the gonadotrophin group were considered to be responsible for the increased costs. In the New Zealand trial the costs of a live birth were one-third lower in the group that underwent laparoscopic ovarian diathermy compared with those women who received gonadotrophins (NZ$19,640 and 29,836, respectively). SUMMARY: Treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in reduced direct and indirect costs. The reduction in multiple pregnancies makes the alternative of surgery particularly attractive.     

Endometrial carcinoma in young women. A report of four cases

Endometrial carcinoma in young women is a rare but well-documented clinicopathologic entity. Four cases revealed some unusual clinical and pathologic features. Patient 1 was the first recorded case of a young woman (aged 24) on maintenance peritoneal dialysis for chronic renal failure who developed endometrial carcinoma with nonvirilizing oligoovulatory polycystic ovarian enlargement. Following subtotal proctocolectomy for familial polyposis coli complicated by a colonic and rectal carcinoma, patient 2 developed, at age 24, a grade 3 endometrial carcinoma in the absence of any risk factors; she was still alive three years postoperatively despite the subsequent development of a grade 3 astrocytoma in the left temporal region. Patient 3 presented at age 32 after ten years of amenorrhea with the clinical features of the Stein-Leventhal syndrome and abnormal uterine bleeding related to a grade 1 endometrial carcinoma; she also had focal dysplasia and adenocarcinoma in situ of the endocervix. Patient 4, who had no risk factors, developed a grade 2 endometrial carcinoma at age 34 despite constant use of combined oral contraceptives for one year and intermittent exposure to them for the previous ten years. Endometrial carcinoma is a rare but important cause of abnormal uterine bleeding in young women; the prognosis can be improved only by prompt diagnosis and appropriate therapy.     

Prävention des Endometriumkarzinoms

To prevent malignant diseases, various strategies are reasonable: screening, avoidance of risk factors, detection and knowledge of preinvasive lesions, screening of special populations with risk factors, and application of protective factors. Screening asymptomatic women for endometrial cancer is generally not warranted. Oral combined contraceptives show significant protective effects; however, their use for preventive measures is limited. For these reasons, understanding of risk factors (hyperestrogenism, polycystic ovary syndrome, chronic anovulation, tamoxifen, obesity, hereditary nonpolyposis colorectal cancer) is important. Awareness of early symptoms (bleeding disturbances, postmenopausal bleeding), diagnosis, and treatment of endometrial hyperplasia is important for preventive reasons and is discussed in detail.     

Combined oral contraceptives and gonadotropin releasing hormone agonistic analogs in polycystic ovary syndrome: clinical and experimental studies

Polycystic ovary syndrome is a common endocrine disorder, presenting with menstrual irregularities, hirsutism, obesity, infertility and abnormal ovarian morphology. In addition, polycystic ovary syndrome is associated with a self-perpetuating imbalance involving the endocrine system and metabolic pathways, in which carbohydrates, lipids and growth factors are involved. Because of its chronicity, it is considered to be a substantial risk factor for atherogenesis and hormone-dependent neoplasia.

The etiology and pathophysiology of the syndrome remain elusive. However, during the last decade, several clues have emerged from human and animal studies that may have significant repercussions in the treatment of polycystic ovary syndrome.

Therapeutic maneuvers should be directed towards the dominant abnormalities present in individual patients with polycystic ovary syndrome. Gonadotropin releasing hormone (GnRH) agonists can directly affect the gonadotropin generator and secondary downstream derangements, whereas combined oral contraceptives (COCs) can modify hypothalamic as well as peripheral abnormalities. In view of the fact that GnRH agonistic analogs (GnRH-a) will induce hypoestrogenemia and its sequelae, the add-back strategy of estrogenic supplementation is recommended for preventive reasons and, as it transpires from some studies, for enhancement of GnRH-a effectiveness.     

PREMENSTRUAL SYNDROME: Current Concepts in Diagnosis and Management

Premenstrual syndrome (PMS), a constellation of physical and psychologic symptoms, is a common complaint among women of reproductive age, particularly women in their 30s or older and among women of greater parity. Symptoms must occur in the luteal phase with resolution or improvement within one or two days of the onset of menses. Numerous hypotheses have been espoused to explain the etiology of PMS, but no definitive cause has been established. The management of PMS may include simple measures such as exercise, dietary changes, and vitamin supplementation. Pharmacologic agents such as progesterone, prostaglandin inhibitors, diuretics, oral contraceptives, or psychotropic drugs may be useful in selected clients. Support and counseling is of paramount importance in the management of PMS. Nurse-midwives can manage women who have minor and transient physiologic and emotional changes associated with mild degrees of PMS. Women with moderate and severe symptoms should be referred for evaluation and follow-up.