Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Maternal anaemia and maternal, fetal, and neonatal outcomes in a prospective cohort study in India and Pakistan.

OBJECTIVE: To describe the association of maternal anaemia with maternal, fetal, and neonatal outcomes. DESIGN: Prospective cohort study. SETTING: Rural India and Pakistan. POPULATION: Pregnant women residing in the study catchment area. METHODS: We performed an analysis of a prospective pregnancy registry in which haemoglobin is commonly obtained as well as maternal, fetal, and neonatal outcomes for 42 days post-delivery. Women 40 years or older who delivered before 20 weeks or had a haemoglobin level of <3.0 g/dl were excluded. Our primary exposure was maternal anaemia, which was categorised in keeping with World Health Organization criteria based on a normal (≥11 g/dl), mild (>10-10.9 g/dl), moderate (7-9.9 g/dl) or severe (<7 g/dl). haemoglobin level. The primary maternal outcome was maternal death, the primary fetal outcome was stillbirth, and the primary neonatal outcome was neonatal mortality <28 days. RESULTS: A total of 92 247 deliveries and 93 107 infants were included, of which 87.8% were born to mothers who were anaemic (mild 37.9%, moderate 49.1%, and severe 0.7%). Maternal mortality (number per 100 000) was not associated with anaemia: normal 124, mild 106, moderate 135, and severe 325 (P = 0.64). Fetal and neonatal mortality was associated with severe anaemia: stillbirth rate (n/1000)-normal 27.7, mild 25.8, moderate 30.1, and severe 90.9; P < 0.0001; 28-day neonatal mortality (n/1000)-normal 24.7, mild 22.9, moderate 28.1, and severe 72.6 (P < 0.0001). Severe maternal anaemia was also associated with low birthweight (<2500 and <1500 g), preterm birth, and postpartum haemorrhage. CONCLUSION: Severe maternal anaemia is associated with higher risks of poor maternal, fetal, and neonatal outcomes but other degrees of anaemia are not. Interventions directed at preventing severe anaemia in pregnant women should be considered. TWEETABLE ABSTRACT: Severe maternal anaemia is associated with adverse fetal and neonatal outcomes in low/middle-income countries.

Clindamycin to reduce preterm birth in a low resource setting: a randomised placebo-controlled clinical trial.

OBJECTIVE: To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH ≥5.0. DESIGN: Randomised double-blind placebo-controlled trial. SETTING: Rural southern India. POPULATION: Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks. METHODS: Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (≥5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks. RESULTS: Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of<2500 g, <1500 g, miscarriage, stillbirth or neonatal death. CONCLUSION: In this setting, oral clindamycin did not decrease PTB among women with vaginal pH ≥5.0. TWEETABLE ABSTRACT: Oral clindamycin between 13+0/7 and 20+6/7 weeks does not prevent preterm birth in women with a vaginal pH ≥5.0.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?

Pharmacologic osteoporosis therapy, particularly anti-resorptives, is recommended in postmenopausal women with clinical risk factors for fracture. Treatment decisions should be made based on the relative benefit-risk profile in different patient populations. Emerging options [e.g., selective estrogen receptor modulators (SERMs) and denosumab] may hold promise for providing protection from bone loss and for fracture risk reduction.Osteoporosis, the most common clinical disorder of bone metabolism, is characterized by low bone mineral density, deterioration of microarchitecture, and a consequent increase in bone fragility and risk of fracture. Pharmacologic therapy is recommended in postmenopausal women with clinical risk factors for fracture and includes anti-resorptive agents such as bisphosphonates, hormone therapy, SERMs, and calcitonin. The anabolic agent teriparatide (parathyroid hormone) is usually reserved for high-risk patients or those with glucocorticoid-induced osteoporosis. Strontium ranelate, available outside the USA, has both anti-resorptive and anabolic properties. Supplementation with calcium and vitamin D is recommended for all women aged 50 years and older. Bisphosphonates are often considered first-line therapy for osteoporosis and have the largest base of clinical trial data showing efficacy for global fracture risk reduction. Low-dose hormone therapy is appropriate for younger women who are experiencing other menopausal symptoms. In women for whom bisphosphonates are not appropriate or not tolerated or in younger postmenopausal women who have a low risk for hip fracture, SERMs are a suitable treatment option. Calcitonin is designated for patients who are unable or unwilling to tolerate other osteoporosis agents. Emerging options, including newer SERMs (e.g., bazedoxifene and lasofoxifene) and the monoclonal antibody denosumab, may hold promise for providing protection from bone loss and for fracture risk reduction. Because no single agent is appropriate for all patients, treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations.

Drape estimation vs. visual assessment for estimating postpartum hemorrhage.

OBJECTIVE: To compare (1) visual estimation of postpartum blood loss with estimation using a specifically designed blood collection drape and (2) the drape estimate with a measurement of blood loss by photospectrometry. METHODS: A randomized controlled study was performed with 123 women delivered at the District Hospital, Belgaum, India. The women were randomized to visual or drape estimation of blood loss. A subsample of 10 drape estimates was compared with photospectrometry results. RESULTS: The visual estimate of blood loss was 33% less than the drape estimate. The interclass correlation of the drape estimate to photospectrometry measurement was 0.92. CONCLUSION: Drape estimation of blood loss is more accurate than visual estimation and may have particular utility in the developing world. Prompt detection of postpartum hemorrhage may reduce maternal morbidity and mortality in low-resource settings.

Postpartum hemorrhage in resource-poor settings.

Despite the strong interest of international health agencies, worldwide maternal mortality has not declined substantially over the past 10 years. Postpartum hemorrhage (PPH) is the most common cause of maternal death across the world, responsible for more than 25% of deaths annually. Although effective tools for prevention and treatment of PPH are available, most are not feasible or practical for use in the developing world where many births still occur at home with untrained birth attendants. Application of many available clinical solutions in rural areas would necessitate substantial changes in government infrastructure and in local culture and customs surrounding pregnancy and childbirth. Before treatment can be administered, prompt and accurate diagnosis must be made, which requires training and appropriate blood measurement tools. After diagnosis, appropriate interventions that can be applied in remote settings are needed. Many uterotonics known to be effective in reducing PPH in tertiary care settings may not be useful in community settings because they require refrigeration and/or skilled administration. Moreover, rapid transfer to a higher level of care must be available, a challenge in many settings because of distance and lack of transportation. In light of these barriers, low-technological replacements for treatments commonly applied in the developed-world must be utilized. Community education, improvements to emergency care systems, training for birth attendants, misoprostol, and Uniject have shown promise as potential solutions. In the short term, it is expedient to capitalize on practical opportunities that utilize the existing strengths and resources in each community or region in order to implement appropriate solutions to save the lives of women during childbirth.

Conducting international collaborative research in developing nations.

International research partnerships bring together some of the best and the brightest in an effort to tackle global health problems. Such collaborations also pose complex challenges, such as maintaining ethical principles in the conduct of research in developing nations. In implementing a randomized clinical trial to reduce postpartum hemorrhage (PPH) during childbirth in rural India, U.S. and Indian collaborators addressed three such issues: the appropriateness of an ethical randomized controlled trial in the developing world, the inclusion of a placebo arm, and the relevance of informed consent in a semiliterate rural population.

Barrier methods of contraception.

Despite the problems associated with coitus-dependent methods of contraception, barrier methods have an important role. The fact that they work as contraceptives without systemic effects makes them particularly appropriate for women with medical conditions that prevent the use of hormonal contraception. In addition, condoms and perhaps all barrier methods provide protection from sexually transmitted infections, making them essential for sexually active women at risk for STDs. Their continued importance is evidenced by the ongoing research to develop and improve barrier methods of contraception.

Androgen excess in women.

There exists a growing body of evidence in women that links androgen excess to increases in cardiovascular disease and reproductive site neoplasia. Ten to fifteen percent of women exhibit clinical signs and symptoms of hyperandrogenism wherein more extensive evaluation is warranted. Women with adult acne, android-type obesity, and alopecia often have been treated for cosmetic reasons without regard to the underlying pathophysiology. Adverse changes in insulin resistance, lipids, and apoproteins favor earlier progression of diabetes for some patients and an unfavorable cardiovascular risk profile for most. Patients with polycystic ovarian syndrome (PCOS) often present to different health providers with different complaints that include excessive facial hair, obesity, hypertension, impaired glucose tolerance, dysfunctional uterine bleeding, or infertility. First-line treatment options, after excluding ovarian or adrenal tumors, include use of non-androgenic OCs until pregnancy is desired. Early identification of patients allows for use of risk-reduction strategies, which may affect clinical outcomes.

Quality of life during sequential hormone replacement therapy -- a placebo-controlled study.

OBJECTIVE -- The purpose of the study was to determine the efficacy of sequential 17 beta-estradiol and norethindrone acetate (Trisequens) in the relief of vasomotor symptoms by comparing the quality of life data from questionnaires, number and severity of symptoms, and the dropout rate versus placebo treatment. STUDY DESIGN -- Women 40 to 60 years old, who spontaneously complained of menopausal symptoms, were randomly allocated to four consecutive cycles with Trisequens (n = 40) or placebo (n = 42). Analysis of variance and two-tailed tests (P < .05) for all comparisons were used. RESULTS -- The mean number of pretreatment vasomotor symptoms per day was 7 (1.3 severe) for Trisequens and 6 (1.8 severe) for placebo, whereas posttreatment a reduction to 1.3 (0.1 severe) versus 4.2 (1.8 severe), respectively, was observed. Quality of life scores, utilizing the Kupperman Scale, 3-Factor Green Index, and Beck Depression Inventory all produced statistically significant differences (P = 0.0015, 0.0037, 0.0026, 0.0003, 0.0242, respectively). The dropout rate difference between groups was significant (P = 0.028): 12 from the Trisequens group and 23 from the placebo group. CONCLUSION -- Trisequens significantly improves vasomotor symptoms. Quality of life rating scales provide additional data to support the utility of sequential estrogen/progestin treatment for menopause therapy.

Effects of sex steroids on women's health: implications for practitioners.

Androgen excess in women is manifested typically by clinical features that may include hirsutism, acne, central obesity, male-pattern baldness, upper torso widening, increased waist-to-hip ratio, clitoral hypertrophy, and deepening of the voice. The differential diagnosis includes androgen-producing ovarian and adrenal neoplasms, Cushing's syndrome, polycystic ovary syndrome, and the intake of exogenous androgens. Physicians treating patients for one symptom of androgen excess must be alert for other symptoms and signs. The cosmetic manifestations of androgen excess belie the serious health risks associated with this condition, including cardiovascular disease, intravascular thrombosis, and insulin resistance. Prompt clinical recognition of androgen excess, understanding of the androgen-related biochemical abnormalities underlying the risks associated with this condition, and implementation of risk modification can reduce the incidence of associated morbidity and mortality. An interdisciplinary approach to management is strongly recommended. Risk reduction strategies include correction of dyslipidemias, low-dose aspirin for primary prevention of myocardial infarction, maintenance of ideal weight, smoking cessation, exercise, use of oral contraceptives containing a low-androgenic progestin, and postmenopausal estrogen replacement. Combination oral contraceptives containing low-androgenic progestins are effective not only in reducing signs of androgen excess but also in potentially retarding the progression of long-term sequelae such as cardiovascular disease.

PIP: 5-10% of all women have an androgen excess syndrome. Androgen excess signs and symptoms include hirsutism, acne, central obesity, male-pattern baldness, upper torso widening, increased waist-to-hip ratio, clitoral hypertrophy, and deepening of the voice. Physicians must be able to recognize these signs and symptoms. Presence of these signs and symptoms calls for a screening history and physical examination. Differential diagnoses of androgen excess in women include endogenous and exogenous causes. Endogenous-related diagnoses are those of ovarian origin (primary tumors, metastatic tumors, polycystic ovary syndrome, ovarian stromal hyperthecosis, androgen excess in pregnancy, and abnormal gonadal or sexual development) and those of adrenal origin (Cushing's syndrome/disease, late-onset congenital adrenal hyperplasia, and tumors). Exogenous causes of androgen excess include Danazol, Phenytoin, Diazoxide, Hexachlorobenzene, Hexachlorophene, Minoxidil, Cyclosporin, testosterone and other androgens, anabolic steroids, synthetic progestins (the pill), and Metapyrone. When physicians treat patients for one symptom of androgen excess, they should watch for other signs and symptoms. Serious health risks associated with androgen excess include cardiovascular disease, intravascular thrombosis, and insulin resistance. Physicians must be aware that timely clinical recognition of androgen excess, knowledge of androgen-related biochemical abnormalities underlying the risks linked to androgen excess, and risk modification behavior reduces associated morbidity and mortality. Risk reduction strategies are correction of dyslipidemias, low-dose aspirin for primary prevention of myocardial infarction, maintenance of ideal weight, smoking cessation, exercise, use of combined oral contraceptives (OCs) with a low-androgenic progestin, and postmenopausal estrogen replacement. OCs also slow progression of long-term sequelae (e.g., cardiovascular disease).

Oral contraceptives and cardiovascular risk. Taking a safe course of action.

Although a prospective, longitudinal study on the long-term cardiovascular effects of oral contraceptives has yet to be performed, available data are useful in determining a safe course of action while physicians await definitive answers. Exogenous sex steroids produce important effects on lipid metabolism. Early intervention against cholesterol is important in reducing cardiovascular risk. Current users of high-dose formulations, particularly older women who smoke, are at greatest risk for cardiovascular complications, especially myocardial infarction. Low-dose oral contraceptives have more modest effects on lipid metabolism, but important differences in the potency of progestins remain. Fortunately, recent studies among users of lower-dose oral contraceptive formulations fail to show an increase in cardiovascular morbidity and mortality. Nonetheless, prudent physicians will avoid oral contraceptives that may adversely affect lipoprotein metabolism, such as those containing progestins with high androgenic and antiestrogenic potency.

PIP: The cardiovascular effects of oral contraceptives, as predicted by studies on serum lipid changes in users, are based on the progestin dose, androgenic potency and biologic effect of the estrogen in the pill. Women suffer 250,000 deaths per year in the U.S. resulting from cardiovascular disease, almost half as many as men. They have the same risk factors: high cholesterol, high blood pressure and smoking, and also have more risk from diabetes than men do. The serum HDL, especially HDL2, correlates closely and inversely with heart disease risk. Exogenous estrogens raise HDL and HDL2, and lower LDL, conferring protection against coronary disease, in direct proportion to dose. Progestins usually have adverse effects, in proportion to dose, but progestin potency and type also determine their effects. The estrane progestins norethindrone, norethindrone acetate and ethynodiol diacetate are less potent and much less androgenic, while the gonanes norgestrel and especially levonorgestrel are 5-20 times as potent and androgenic. Each pill needs to be considered as a unit. Several comparative studies are reviewed, corroborating the prediction that pills with higher progestin potency have adverse effects on serum lipids, compared to those with higher estrogen effect. For new lower dose multiphasics, the effects either way are minimal, but HDL2 is still significantly lowered by pills containing levonorgestrel. Progestin-only pills lower HDL2 17- 21%. It is prudent to follow and treat the long-term effects of oral contraceptives on blood lipids.

[Clinical evidence of the minimal androgenic activity of norgestimate]. / Preuve clinique de l'activité androgénique minimale du norgestimate.

The aim for improving the progestogen component of oral contraceptives is both to increase their selectivity by obtaining a highly effective contraceptive action and to decrease the side effects related to the existing progestogens. The androgenic activity of the existing progestogens modifies the lipid metabolism, particularly a decrease in the high density lipoprotein (HDL) level, which increases the risks of cardiovascular diseases. Thus, the discovery of a progestogen with good anti-ovulatory and minimal androgenic properties would constitute an important progress in the field of oral contraception. Norgestimate (NGM) is a new progestogen presenting an exceptional profile of biological activity, and has proved to be extremely selective, as observed during the clinical trials. The studies described below have been carried out in order to confirm clinically the low androgenic activity of NGM. In two clinical trials, Norgestimate (0.25 mg) associated with 0.035 mg of ethinyloestradiol (NGM 0.25/35) was compared to norgestrel (0.30 mg) associated with 0.030 mg of ethinyloestradiol (Lo/Ovral). In the first trial (1,261 women), the following observations were made: an important increase in the HDL level compared to the base levels in the subjects taking NGM 0.25/35, and an important decrease in the HDL level in those taking Lo/Ovral. The low density lipoprotein (LDL) level increased slightly in the NGM 0.25/35 group, while a higher increase was observed in the Lo/Ovral group. Moreover, the LDL/HDL ratio translates a more favourable lipid profile in the NGM 0.25/35 group, since the values are lower than those observed for the Lo/Ovral group.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of light support pantyhose.

The results of a multicenter, double-blind clinical trial indicate that the use of light support pantyhose significantly reduced the incidence of aches, swelling and fatigue in the lower legs of healthy women. A trend toward reduced foot and leg circumference was noted; however, it did not correlate significantly with subjective symptomatology.

Clinical evidence of the minimal androgenic activity of norgestimate.

The goal in improving the progestational component of oral contraceptives (OCs) is to enhance the selectivity of the progestin by achieving a high degree of contraceptive efficacy while decreasing undesirable side effects associated with existing progestational agents. The androgenic activity of current progestins results in changes in lipid metabolism, particularly decreased levels of high-density lipoprotein cholesterol (HDL), which have been associated with an increased risk of coronary heart disease (CHD). A progestin with high antiovulatory activity and minimal androgenicity would offer a clear therapeutic advantage in oral contraception. Norgestimate (NGM) is a new progestin with a unique profile of biological activity that has demonstrated a high level of selectivity in preclinical assays. The present studies were conducted to confirm clinically the low androgenic activity of NGM. Norgestimate (0.25 mg) in combination with 0.035 mg ethinyl estradiol (NGM 0.25/35) was compared with 0.30 mg norgestrel combined with 0.030 mg ethinyl estradiol (Lo/Ovral) in two multicenter clinical studies. In the first study (1,261 women), HDL levels were significantly increased from baseline levels in NGM 0.25/35 subjects but were significantly decreased in Lo/Ovral subjects. Increases in low-density lipoprotein cholesterol (LDL) levels were moderate in the NGM 0.25/35 group and pronounced in the Lo/Ovral group. A favorable lipid profile in NGM 0.25/35 subjects was also reflected in the LDL/HDL ratios, which were significantly lower in the NGM 0.25/35 subjects than in the Lo/Ovral subjects. Sex hormone binding globulin (SHBG) binds androgens, preventing clinical expression of androgenic activity. As a result, elevations in SHBG levels reduce bioactive (unbound) androgen levels and decrease the potential for androgenic side effects.(ABSTRACT TRUNCATED AT 250 WORDS)