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PubMed2004

Does metformin induce ovulation in normoandrogenic anovulatory women?

OBJECTIVE: This study was undertaken to evaluate the efficacy of metformin in women with anovulation who do not have evidence for hyperandrogenism and classic polycystic ovary syndrome. STUDY DESIGN: A randomized trial of metformin (1500 mg daily) and placebo in 24 anovulatory women was undertaken for 3 months. Assessments of changes in hormone levels and insulin sensitivity were carried out. Abnormal hormonal values were defined by levels exceeding the range in normal ovulatory controls. RESULTS: Anovulatory women had normal androgen levels and luteinizing hormone but had higher serum insulin and lower insulin sensitivity compared with controls. Over 3 months, there were 16 ovulatory cycles with metformin and only 4 with placebo ( P < .05). Success of ovulation did not correlate with changes in androgen, insulin, or insulin sensitivity parameters. CONCLUSION: Metformin may be useful for inducing ovulation in anovulatory women who do not have hyperandrogenism. This effect may be independent of a lowering of androgen or insulin levels.

Adult↗
PubMed2005

Genitourinary symptoms in the menopausal transition.

Irregular uterine bleeding is a common symptom among women in the menopausal transition. Women commonly transition from having regular cycles to having irregular cycles before the final menstrual period. In late perimenopause, anovulation becomes more common, leading to skipped menstrual cycles. Low-dose oral contraceptive pills are effective in decreasing the amount of menstrual blood loss and improving menstrual cycle regularity. It is unclear whether menorrhagia is associated with normal perimenopausal hormonal changes. Studies to date have failed to correlate menorrhagia with hormonal levels and pathology within the uterus. Because of the common association between uterine pathology and menorrhagia, this is an important area for future studies. Vaginal dryness is a common symptom, particularly in late perimenopause. The association between vaginal dryness and low estrogen levels is clear. Estrogen-based hormone replacement therapy is effective in treating this symptom. Locally released estrogen therapy may be preferred over systemic therapy because of lower systemic estradiol levels, reduced side effects, and high efficacy. The long-term safety of these products, particularly in women with a history of breast cancer, requires more study. The prevalence of incontinence increases as women age, but it is unclear whether the menopausal transition is an independent risk factor. Incontinence is a frequent complaint among women in the menopausal transition. In postmenopausal women, hormone therapy (HT) appears to be ineffective in preventing or improving the symptoms of incontinence. Further study of HT, including locally applied estrogens for the common symptom of incontinence, are needed in women in the menopausal transition.

Female↗
PubMed2005

Body condition and suckling as factors influencing the duration of postpartum anestrus in cattle: a review.

Prolonged postpartum anestrus is a main factor limiting reproductive efficiency in cattle, particularly in Bos indicus and Bos taurus/Bos indicus cows from tropical regions, because it prevents achievement of a 12 month calving interval. During anestrus, ovulation does not occur despite ovarian follicular development, because growing follicles do not mature. Although many factors affect postpartum anestrus, nutrition and suckling are the major factors influencing the resumption of postpartum ovarian cycles, as they affect hypothalamic, pituitary and ovarian activity and thus inhibit follicular development. Under-nutrition contributes to prolonged postpartum anestrus, particularly among cows dependent upon forages to meet their feed requirements and it apparently interacts with genetic, environmental or management factors to influence the duration of anestrus. The nutritional status or balance of an animal is evaluated through body condition score (BCS), as it reflects the body energy reserves available for metabolism, growth, lactation and activity. There is a converse relationship between energy balance and time to resumption of postpartum ovarian activity; inadequate nutrient intake results in loss of weight and BCS and finally cessation of estrous cycles. Suckling interferes with hypothalamic release of GnRH, provoking a marked suppression in pulsatile LH release, resulting in extended postpartum anestrus. The effects of suckling on regulation of tonic LH release are determined by the ability of the cow to identify a calf as her own or as unrelated. Vision and olfaction play critical roles in the development of the maternal-offspring bond, allowing the cow to identify her own calf, and abolition of both senses attenuates the negative effects of suckling on LH secretion. Thus, the maternal-offspring bond is essential for prolonged postpartum suckling-induced anovulation, and the suppressive influence of suckling is independent of neurosensory pathways within the teat or udder.

Anestrus↗
PubMed2004

Ovarian and hormonal responses to a progesterone-releasing controlled internal drug releasing treatment in dietary-restricted goats.

An experiment was conducted to evaluate the effects of dietary restriction on ovarian, endocrine (ovarian steroids and luteinizing hormone (LH) pulse) and metabolic (glucose, insulin and non-esterified fatty acid (NEFA)) profiles in goats treated with a progesterone-releasing controlled internal drug releasing (CIDR-G) device. Cycling goats were offered either a maintenance or a restricted (30% of requirement; n =4 per treatment) level of feeding. The dietary restriction was started on the day following ovulation. At 30-32 days after the start of food restriction, the goats received a prostaglandin F(2alpha) (2mg of dinoprost) injection followed by 10 days of CIDR-G treatment. Ovarian ultrasonographic images were monitored daily throughout the experiment and blood samples were collected daily just before the morning feeding for analysis of endocrine and metabolic profiles. Frequent blood samples (1 ml) were also collected at 10 min intervals for 8 h from -8 h to CIDR-G removal, and from 32 to 40 h after CIDR-G removal for analysis of LH pulses. Body weight was significantly (P < 0.05) decreased in the food-restricted animals. Oestrous behaviour and ovulation followed by a rise of plasma progesterone concentration were observed after the CIDR-G removal in all control animals but not in any of the food-restricted animals within 12 days after CIDR-G removal. The LH pulse frequency from 32 to 40 h after the CIDR-G removal was significantly (P < 0.05) lower in the food-restricted animals than in control animals (1.5 +/- 0.6 versus 3.8 +/- 0.5 pulses for 8 h). There was no significant difference in the glucose concentration in weekly plasma samples between control and food-restricted animals. Insulin concentrations from 2 weeks after the start of feed restriction were significantly (P < 0.05) lower in restricted animals than in control animals. The NEFA concentration in restricted animals was significantly (P < 0.05) increased after the start of feed restriction, and then decreased gradually to the basal level. The present results suggest that nutritionally induced anovulation after CIDR-G treatment is associated with a reduction in the frequency of LH pulses, and that insulin and NEFA, rather than the glucose concentration in the circulation, may be associated with the metabolic suppression of LH pulses.

Animals↗
PubMed2004

Hirsutism and acne in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality affecting reproductive age women. Population-based studies estimate a prevalence of 5-10% [Obstet Gynecol 101 (2003) 995; Aust N Z J Obstet Gynaecol 41 (2001) 202]. The clinical characteristics of PCOS include hyperandrogenism, chronic anovulation, insulin resistance and infertility. Hyperandrogenism is generally manifested as hirsutism and acne. Both these clinical symptoms are treated with similar drug therapies, including oral contraceptive pills (OCPs), topical medications or antiandrogens such as spironolactone, flutamide and finasteride, as well as topical medications. Recent studies have shown that lower doses of these medications are as efficacious as high doses and have the advantage of decreased cost and an improved side-effect profile. Although hirsutism and acne can be considered cosmetic in nature, they cause significant social embarrassment and emotional distress. Physicians should be sensitive to these issues and approach patients in a caring and sympathetic manner.

5-alpha Reductase Inhibitors↗
PubMed2004

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.

Abortion, Spontaneous↗
PubMed2004

Insulin resistance and metformin in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with widespread systemic manifestations affecting 5-10% of women of reproductive age. The accompanying insulin resistance and hypeinsulinemia mark this syndrome as a prediabetic state, with high incidence of impaired glucose tolerance, gestational diabetes, and overt diabetes. Other metabolic and biochemical changes, such as hypertension and dyslipidemia, increase the risk of cardiovascular disease. Fertility may also be impaired due to anovulation, impaired implantation, and higher rates of spontaneous abortions. All of these effects may also be related to hyperinsulinemia. Metformin, as insulin-sensitizing drug, is being evaluated for its potential long-term disease-modifying effect, such as prevention of diabetes. Its use may also help restore spontaneous ovulation and improve menstrual cyclicity, improve the success rate of induction of ovulation with clomiphene citrate and FSH, and decrease the high rate of ovarian hyperstimulation and early pregnancy loss. Nevertheless, these new exiting potential benefits of metformin should be evaluated in large randomized controlled studies, and clinicians must counsel women appropriately before the initiation of metformin therapy.

Cardiovascular Diseases↗
PubMed2004

FSH and LH together in ovarian stimulation.

The authors review the physiology of the ovulatory cycle and the role of the gonadotrophins in ovulation induction in patients with anovulatory disorders and in multifollicular development for assisted reproductive technologies. The use of gonadotrophins with luteinizing hormone (LH) activity and the use of recombinant LH associated with follicle stimulating hormone (FSH) are discussed. The authors point out that administration of gonadotrophins with LH activity is essential in hypogonadotropic hypogonadal anovulation, and data available in the medical literature allow the conclusion that recombinant LH may be added to all ovarian stimulation protocols because it is difficult to determine which patients will benefit from LH administration and there is no evidence that LH affects adversely the outcome of ovarian stimulation. The use of recombinant LH in addition to recombinant FSH may be particularly useful when a GnRH antagonist is associated with the ovarian stimulation regimen, by preventing the fall in estradiol and diminishing FSH requirements.

Drug Therapy, Combination↗
PubMed2005

Pregnancy outcomes and deliveries following laparoscopic transsection of uterine vessels: a pilot study.

OBJECTIVE: To assess pregnancy outcomes and deliveries after laparoscopic uterine artery transsection (LTUV) in symptomatic women with fibroids. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Center, Baby Friendly Hospital, Kladno, Czech Republic. DESIGN: One hundred and fifty three patients underwent laparoscopic transsection of uterine vessels during a 4-year period. RESULTS: Nine of the 21 women desiring pregnancy conceived spontaneously and one after anovulation treatment. The average age of the women was 32.4 years, and the range was 26-39 years. Two women had vaginal delivery at term and one delivered vaginally at 31 weeks secondary to premature preterm rupture of membrane (PROM). Four others delivered at term by cesarean section. One woman with placenta previa was delivered by cesarean section 3 weeks before term. Mean birth weight was 3199 g (range 1710-3910 g). One spontaneous abortion was reported in the first trimester of pregnancy. One case of undesired pregnancy occurred. An extrauterine pregnancy was reported in this woman. CONCLUSION: LTUV is a minimally invasive operative procedure, that preserves the uterus and ovarian blood supply and allows for the achievement of pregnancy in women with symptomatic fibroids. Fetal growth and umbilical Doppler findings remained normal in all cases. An increased risk for preterm delivery and cesarean section was found in this small series.

Adult↗
PubMed2006

Polycystic ovarian syndrome, insulin resistance and thickness of the endometrium.

INTRODUCTION: Disorders possibly associated with insulin resistance (IR) are hyperandrogenemia, hirsutism, irregular menstrual cycles, central obesity and polycystic ovarian syndrome (PCOS). It is known that PCOS is related to a high risk of endometrial hyperplasia after many years of estrogen stimulation from anovulation. OBJECTIVES: The purpose of the study was to estimate the thickness of the endometrium in women with IR without a diagnosis of PCOS and in women with PCOS without IR. STUDY DESIGN: Three groups of women included in the study: 15 women diagnosed as IR without PCOS, 16 women diagnosed as PCOS without IR and 20 women used as controls matched for age and body mass index (BMI) with the previous patients. Thickness of the endometrium was estimated in all cases with a transvaginal ultrasound in three consecutive measures during a cycle. RESULTS: The mean thickness of the endometrium was statistically higher in the PCOS group (11.1mm), and in the IR group (9.6mm), compared with the control group (6.2mm) (F=13.1, p<0.001). CONCLUSIONS: It is concluded that both in women diagnosed as having insulin resistance without PCOS, and in women with PCOS without insulin resistance, the ultrasonographically estimated thickness of the endometrium is relatively high and a closer follow-up of these women is required in order to detect those in risk to develop hyperplasia and/or atypia.

Adult↗
PubMed2005

Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization.

OBJECTIVE: To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients. DESIGN: Randomized, prospective analysis. SETTING: Private hospital incorporating an established IVF center. PATIENT(S): Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness. INTERVENTION(S): Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily. MAIN OUTCOME MEASURE(S): A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated. RESULT(S): With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented. CONCLUSION(S): After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH.

Adult↗
PubMed2005

Growth hormone secretion and insulin-like growth factor-1 are related to hyperandrogenism in nonobese patients with polycystic ovary syndrome.

Women of normal weight with polycystic ovary syndrome (PCOS) and hyperinsulinemia presented high growth hormone (GH) levels in response to the l-dopa test, suggesting that the action of GH and insulin-like growth factor-1 (IGF-1) might be responsible for the elevation in LH and the consequent hyperandrogenic anovulation observed in normal weight women with PCOS. Insulin resistance and obesity are related to a reduction in GH secretion in obese women with PCOS.

Adult↗
PubMed2006

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.

Adult↗
PubMed2005

[MRI of the pituitary gland: indications and results in gynaecology and in obstetrics].

MRI is the sole radiological examination to be obtained if abnormal menses, galactorrhea or anovulation evokes the diagnosis of prolactinoma. Nevertheless, iatrogenic hyperprolactinemia or presence of big prolactin has to be ruled out before MRI is asked for. MRI of the pituitary gland must be technically optimal; analysis of the images has to be directed by clinical and biological data.

Amenorrhea↗
PubMed2005

[Breastfeeding and breast cancer].

The objective of this review is to summarize the current knowledge about the impact of pregnancy and lactation on the risk of breast cancer and possibility of breastfeeding after breast cancer treatment. A Pubmed search was carried out for publications in English or French from 1974 through 2004, related to breast cancer, pregnancy and breastfeeding. There is a transient increase in risk of breast cancer in the first three to four years after pregnancy, whereas during lifetime, the risk seems lower than in nulliparity. Lactation reduced the risk for breast cancer. This protective effect seems greater for women who had extended periods of breastfeeding during their lifetime, particularly in case of BRCA1 mutation. Various physiopathological mechanisms are involved in the protective effect of breastfeeding: anovulation, cellular differentiation of the mammary cells and excretion in the milk of breast carcinogens. After breast cancer treatment, there is no evidence that breastfeeding increases the risk of breast cancer recurrence, nor that it carries any health risk to the newborn. Women previously treated for breast cancer and free of recurrence are allowed to breastfeed their children. Beneficial effects of breastfeeding for the mother and the newborn should lead physicians and midwives to encourage prolonged breastfeeding in their medical practice.

Breast Feeding↗
PubMed2006

[Rotterdam consensus in adolescent girls: which investigations and how to interpret them to make the diagnosis of PCOS?].

The polycystic ovary syndrome (PCOS) is the most frequent cause of hyperandrogenism and anovulation in adult women as well as in adolescent girls. Since 2003 the diagnosis of PCOS has been based on the association of hyperandrogenism, oligoanovulation and polycystic ovary (PCO) morphology at ultrasound (at least 2 items out of 3). In adolescents however, PCOS features may be difficult to distinguish from the symptoms of the end of puberty. Moreover, transvaginal ultrasound examination is seldom possible, and it is difficult to get precise imaging of the ovaries by abdominal route. However, the diagnosis of PCOS in a hyperandrogenic and/or oligomenorrheic adolescent requires on the strict application of the Rotterdam criteria, as in adult women. Priority should be given to clinical features whereas pelvic ultrasound must be considered as optional. Few hormonal assays will serve mainly to make the differential diagnosis, in addition to clinical findings. Once established, the diagnosis of PCOS in an adolescent girl must lead to the detection of the metabolic syndrome by means of simple investigations. This will allow early prevention of its complications.

Adolescent↗
PubMed2006

[Psychogenic amenorrhea].

Any amenorrhoea noticed outside pregnancy, lactation and menopause periods might be of organic or functional origin. Today, non organic amenorrhoea are either called hypothalamic amenorrhoea, more exactly supra hypothalamic amenorrhoea; functional amenorrhoea--this definition being characterized by its lack of any anatomic substratum; or, psychogenic amenorrhoea--an etiologic definition. Like any amenorrhoea, functional or psychogenic amenorrhoea is the consequence of either anovulation or endometrial hypotrophy. Neuroendocrine sciences do open new exciting research perspectives but other ways all the more promising since hormonal mechanics would not be the explanation. Work on the unconscious is indeed the other road leading to these psychogenic amenorrhoea. The term "psychogenic"--of psychological origin--does not mean of unknown origin, provided we recognize the strong link between psyche and soma. Treatment for this kind of amenorrhoea is twofold: medical and psychotherapeutic. Even though psychological etiology is obvious, clinical examination must be rigorous and completed by complementary exams which will guide the therapeutics. This is reassuring to the patient for the gynaecologist she chose to consult is implied, and not the psychotherapist. This reassures us too, because what we care for, as doctors, is first of all the body. Psychotherapeutic support can be provided by the general practitioner or the gynaecologist, both with psychosomatics training, but a multidisciplinary approach must often be worked out.

Amenorrhea↗
PubMed2005

Gynecological health of females with congenital heart disease.

Because of major advances in diagnostic and surgical methods, females with congenital heart disease (CHD) now survive into and beyond their reproductive years. Management of pregnancy in this patient population is well described, but gynecologic management such as menstruation, contraception and menopause have received scanty attention. Accordingly, the gynecologic health issues confronting these patients are described. Menstrual patterns in acyanotic females with CHD are similar to the general population, but cyanotic females have menstrual irregularities including amenorrhea, which implies anovulation and an increased risk of uterine carcinoma. Anticoagulants predispose to heavy vaginal bleeding and corpus luteum rupture. Contraceptives must be selected according to individual patient profiles. Hormone replacement therapy is warranted for relief of menopausal symptoms as in the general population and should be relatively safe because estrogen dose is low.

Abortion, Induced↗