A significant number of women with migraine has to face the choice of reliable hormonal contraception during their fertile life. Combined hormonal contraceptives (CHCs) may be used in the majority of women with headache and migraine. However, they carry a small, but significant vascular risk, especially in migraine with aura (MA) and, eventually in migraine without aura (MO) with additional risk factors for stroke (smoking, hypertension, diabetes, hyperlipidemia and thrombophilia, age over 35 years). Guidelines recommend progestogen-only contraception as an alternative safer option because it does not seem to be associated with an increased risk of venous thromboembolism (VTE) and ischemic stroke.
Potentially, the maintenance of stable estrogen level by the administration of progestins in ovulation inhibiting dosages may have a positive influence of nociceptive threshold in women with migraine. Preliminary evidences based on headache diaries in migraineurs suggest that the progestin-only pill containing desogestrel 75 μg has a positive effect on the course of both MA and MO in the majority of women, reducing the number of days with migraine, the number of analgesics and the intensity of associated symptoms. Further prospective trials have to be performed to confirm that progestogen-only contraception may be a better option for the management of both migraine and birth control. Differences between MA and MO should also be taken into account in further studies.
Migraine with aura (MA); Migraine without aura (MO); Combined hormonal contraceptives (CHCs); Combined oral contraceptives (COCs); Progestogen-only contraception; Desogestrel-only pill; Venous thromboembolism (VTE); Stroke
Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%–8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality.
drospirenone; premenstrual dysphoric disorder; premenstrual syndrome; oral contraceptive pill
The use of hormonal contraception (HC) is increasing in HIV-infected women. Both HC and HIV infection have been associated with adverse metabolic outcomes. We investigated the association of progestin-only and combined (estrogen/progestin) HC with disorders of glucose and lipid metabolism in HIV-infected and uninfected women.
Linear mixed models evaluated the association of HC type with fasting HDL, LDL, triglycerides, the homeostasis model assessment estimate of insulin resistance (HOMA-IR), and glucose in 885 HIV-infected and 408 HIV-uninfected women from the Women's Interagency HIV Study seen between October 2000 and September 2005.
Compared to non-HC users, progestin-only HC was independently associated with lower HDL (-3mg/dL;95% confidence interval[CI]:-5,-1 in HIV-infected and -6mg/dL;95% CI:-9,-3 in HIV-uninfected women), greater HOMA (+0.86;95% CI:0.51,1.22 and +0.56;95% CI:0.12,1.01). Combined HC was associated with higher HDL(+5mg/dL;95% CI:2,7 and +5mg/dL;95% CI:3,7).
Progestin–only HC is associated with lower HDL and greater HOMA-IR than non-HC users. Combined HC may be preferred in HIV-infected women of reproductive age at risk for cardiovascular disease, but interactions with antiretroviral therapy that may impair contraceptive efficacy have been reported. Alternative HC methods that minimize adverse outcomes but maintain efficacy require further study.
HIV/AIDS; hormonal contraception; Depo Provera®; HDL; triglycerides
Data on 2,754 cases and 18,565 controls from a multinational hospital-based, case-control study were analysed to determine whether observed associations between combined oral contraceptives and breast cancer are similar for oral contraceptives with varying types and doses of oestrogens and progestins. After stratifying on duration of use, risk was found to be increased in current and recent users, and to decline with time since last use. These associations, of similar strength, were observed for users of products that contain mestranol and ethinyl estradiol, for women who used preparations with progestins derived from 19-nortestosterone and 17-alpha-hydroxyprogesterone, and for those who took preparations with relatively higher and lower doses of oestrogen. When products with equal doses of the same oestrogen or progestin and varying doses of the other hormonal constituent were considered, slightly higher relative risks per year of use were estimated for users of products with relatively higher than lower doses of either the constituent oestrogen or progestin, but the differences in relative risk could readily have occurred by chance. This study provides no evidence that risk of breast cancer in users of oral contraceptives varies by the type of oestrogen or progestin consumed.
The combined oral contraceptive pill (COC) consisting of drospirenone 3 mg/ethinyl estradiol 20 μg (3 mg DRSP/20 μg EE-24/4) supplies 24 days of pills with hormones followed by 4 days of hormone-free pills. This regimen is called the 24/4 regimen. The progesterone component of this oral contraceptive pill (OCP), drospirenone (DRSP), is a fourth-generation progestin that has potent progestogenic, antimineralocorticoid, and antiandrogenic activity, which are unique characteristics compared with the other progestogens contained in most of the other OCPs currently marketed. This formulation, in addition to being an effective long-term OCP, has the additional medical benefit of providing a good parallel treatment for premenstrual dysphoric disorder and moderate acne. The effectiveness of 3 mg DRSP/20 μg EE-24/4, its tolerability and safety, and its additional non-contraceptive benefits are discussed.
drospirenone; premenstrual dysphoric disorder; acne vulgaris; contraception; antimineralocorticoid activity; antiandrogenic activity
The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.
Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with non-psychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (N=950), perimenopausal (N=380), or postmenopausal (N=562). These comparisons were also made between postmenopausal women (n=768) taking (N=171) or not taking (N=562) hormone therapy.
After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than either peri- or postmenopausal women, and were more likely to have decreased appetite and less likely to have early morning insomnia than perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than either of the other groups, and were more likely to have sympathetic arousal and gastrointestinal symptoms than premenopausal women. After adjusting for baseline differences, postmenopausal women taking hormone therapy had better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities than women not taking hormone therapy.
Menopausal status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women.
menopause; hormone therapy; depression; major depressive disorder
Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are commonly comorbid conditions that result in greater severity, chronicity, and impairment compared with either disorder alone. However, previous research has not systematically explored the potential effects of the psychotic subtyping of MDD and comorbid PTSD.
The sample consisted of psychiatric outpatients diagnosed with psychotic MDD with PTSD, psychotic MDD without PTSD, and nonpsychotic MDD with PTSD presenting for clinic intake. Clinical indices of severity, impairment, and history of illness were assessed by trained diagnosticians using the Structured Clinical Interview for DSM-IV supplemented by items from the Schedule for Affective Disorders and Schizophrenia.
In terms of current severity and impairment, the psychotic MDD with PTSD and psychotic MDD only groups were similar to each other, and both tended to be more severe than the nonpsychotic MDD with PTSD group. In terms of history of illness, the psychotic MDD with PTSD group tended to show greater severity and impairment relative to either the psychotic MDD only or nonpsychotic MDD with PTSD groups. Furthermore, the psychotic MDD with PTSD patients had an earlier time to depression onset than patients with either psychotic MDD alone or nonpsychotic MDD with PTSD, which appeared to contribute to the poorer history of illness demonstrated in the former group.
Future research should explore the possibility of a subtype of psychotic depression that is associated with PTSD, resulting in a poorer course of illness. The current findings highlight the need for pharmacological and psychotherapeutic approaches that can be better tailored to psychotic MDD patients with PTSD comorbidity.
major depression; posttraumatic stress disorder; psychosis; comorbidity; psychiatric outpatients; onset of illness
Females with a lifetime diagnosis of major mood disorder (Bipolar Disorder BD, Major Depressive Disorder MMD) investigated during the luteal phase of their menstrual cycle and in a condition of clinical well-being showed higher blood serum concentrations of progesterone and allopregnanolone compared to healthy controls. Women with BD presented even higher levels than those affected by MDD. This study attempted to verify, in line with a dimensional approach, if the possible differences in neurohormonal levels may be directly linked to some syndromal clusters (dimensions) of the mood spectrum disorders indipendently of diagnosis.
Premenstrual concentrations of allopregnanolone, THDOC, progesterone, and cortisol were measured in 3 groups of women: 17 BD and 14 MDD outpatients, and 16 control subjects. Psychiatric evaluation was performed with the SCID-I interview and the SCI-MOODS-SR questionnaire. The correlation between steroid levels and mood disorder syndromal cluster (SCI-MOODS-SR domains and sub-domains) was evaluated by means of analysis of main components with Varimax rotation and Kaiser's normalization (which provided for inclusion of all components with an Eigen value >1).
Analysis of the main components evidenced the presence of 3 components: 1) mania, 2) depression both with mixed component 3) steroid + manic cognitivity and suicidal ideas.
Levels of allopregnanolone and progesterone do not correlate with the association of the depressive and manic syndromes, but rather with mixed symptomatological aspects, and in particular with cognitive manic and depressive (with suicidal thoughts) dimensions. Further studies should be carried out to confirm these findings.
Acne is a common disorder affecting the majority of adolescents and often extends into adulthood. The central pathophysiological feature of acne is increased androgenic stimulation and/or end-organ sensitivity of pilosebaceous units leading to sebum hypersecretion and infundibular hyperkeratinization. These events lead to Propionibacterium acnes proliferation and subsequent inflammation. Hormonal therapy, including combined oral contraceptives (OCs), can attenuate the proximate androgenic trigger of this sequence. For many women, hormonal therapy is a rational option for acne treatment as it may be useful across the spectrum of severity. Drospirenone (DRSP) is a unique progestin structurally related to spironolactone with progestogenic, antimineralocorticoid, and antiandrogenic properties. It is available in 2 combined OC preparations (30 μg EE/3 mg DRSP; Yasmin® in a 21/7 regimen; and 20 μg EE/3 mg DRSP; Yaz® in a 24/4 regimen). These preparations are bereft of the fluid retentional side effects typical of other progestins and their safety has been demonstrated in large epidemiological studies in which no increased risk of vascular thromboembolic disease or arrhythmias was observed. In acne, the efficacy of DRSP-containing OCs has been shown in placebo-controlled superiority trials and in active-comparator non-inferiority trials.
acne vulgaris; combined oral contraceptives; drosperinone; ethinyl estradiol; efficacy; safety; treatment
Fertile women may be encouraged to use contraception during clinical trials to avoid potential drug effects on fetuses. However, hormonal contraception interferes with pharmacokinetics and pharmacodynamics and modifies internal milieus. Macrophages depend on the milieu to which they are exposed. Therefore, we assessed whether macrophage function would be affected by the use of combined oral contraceptives (OCs) and if this influence depended on the androgenic or non-androgenic properties of progestin.
Healthy adult women were enrolled and stratified into two groups: women who did not use OCs (Fs) and women treated with OCs (FOCs). FOCs were further stratified as a function of androgenic (FOCA+) and non-androgenic (FOCA-) properties of progestins. Routine hematological, biochemical, inflammatory and endothelial dysfunction parameters were measured. Monocyte-derived macrophages (MDMs) were evaluated for the expression and activity of estrogen receptors and androgen receptors, and release of tumor necrosis factor α (TNFα) was measured from unstimulated and lipopolysaccharide-stimulated cells.
As is already known, the use of OCs changed numerous parameters: the number of lymphocytes, iron levels, total iron-binding capacity of transferrin, triglycerides, high-density lipoprotein, total cholesterol, and C-reactive protein increased, while prothrombin time and alkaline phosphatase decreased. Hormonal levels also varied: cortisol was higher in FOCs, while luteinizing hormone, follicle-stimulating hormone, and testosterone were lower in FOCs. Asymmetric dimethylarginine, an index of endothelial function, was lower in FOC than in Fs, as were cysteine and bilirubin. The androgenic properties of progestins affected the activity of OCs: in particular, white blood cell count, hemoglobin, high-density lipoprotein and calcium were higher in FOCA- than in FOCA+, whereas percentage oxygen saturation and γ-glutamyl transpeptidase were lower in FOCA- than in FOCA+. Importantly, FOCs had a lower global DNA methylation, indicating that OC may have epigenetic effects on gene expression. OC did not modify the expression of androgen receptor but increased estrogen receptor α expression, more considerably in FOCA+, and decreased estrogen receptor β, more considerably in FOCA-. Importantly, the activation state of estrogen receptor β in FOCs was decreased, while estrogen receptor α was not active in either Fs or FOCs. Unstimulated MDMs obtained from FOCs showed higher release of TNFα in comparison with Fs. After lipopolysaccharide stimulation, the release of TNFα was significantly higher in Fs than in FOCs.
OC use induced many changes in hematological and plasmatic markers, modifying hormonal levels, endothelial function, inflammation index and some redox state parameters, producing a perturbation of the internal milieu that impacted macrophagic function. In fact, different levels of estrogen receptor expression and release of TNFα were observed in macrophages derived from OC users. Some of the above activities were linked to the androgenic properties of progestin. Even though it is not known whether these effects are reversible, the results indicate that to avoid potential skewing of results only a single type of OC should be used during a single clinical trial.
androgenic and non-androgenic progestin; combined oral contraceptive; estrogen receptors; global DNA methylation; monocyte-derived macrophages; TNFα
Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD.
depression; emotionality; testosterone; unpredictable chronic mild stress; sex difference; development
Many women in their reproductive years experience some mood, behavioral. or physical symptoms in the week prior to menses. Variability exists in the level of symptom burden in that some women experience mild symptoms, whereas a small minority experience severe and debilitating symptoms. For an estimated 5%–8% of premenopausal women, work or social functioning are affected by severe premenstrual syndrome. Many women in this group meet diagnostic criteria for premenstrual dysphoric disorder (PMDD). Among women who suffer from PMDD, mood and behavioral symptoms such as irritability, depressed mood, tension, and labile mood dominate. Somatic complaints, including breast tenderness and bloating, also can prove disruptive to women's overall functioning and quality of life. Recent evidence suggests that individual sensitivity to cyclical variations in levels of gonadal hormones may predispose certain women to experience these mood, behavioral, and somatic symptoms. Treatments include: antidepressants of the serotonin reuptake inhibitor class, taken intermittently or throughout the menstrual cycle; medications that suppress ovarian cyclicity; and newer oral contraceptives with novel progestins. (Harv Rev Psychiatry 2009;17:120–137.)
mood disorders; premenstrual dysphoric disorder; premenstrual syndrome
Some women with depressive disorders experience severe premenstrual symptoms. However, there have been few studies in which premenstrual symptoms in women suffering from depressive disorders were assessed. In this study, we aimed to investigate premenstrual symptoms in women with depressive disorders using the premenstrual dysphoric disorder (PMDD) scale.
We administered questionnaires to 65 Japanese female outpatients who had been diagnosed with a major depressive disorder or dysthymic disorder and to 303 healthy women as control subjects. The questionnaire consisted of items on demographics and the PMDD scale, which was modified from the premenstrual symptoms screening tool (PSST) developed by Steiner et al. (Arch Womens Ment Health 2003, 6:203-209).
Twenty-eight women (43.1%) with depressive disorder fulfilled certain items of the PMDD scale. These women are considered to have coexisting PMDD and a depressive disorder, or to have premenstrual exacerbation (PME) of a depressive disorder. On the other hand, 18 women (5.9%) in the control group were diagnosed as having PMDD. The depressive disorder group who fulfilled the PMDD criteria had more knowledge of the term premenstrual syndrome (PMS) and took more actions to attenuate premenstrual symptoms than the control group with PMDD.
Our findings demonstrated that the occurrence of severe premenstrual symptoms is much higher in women with depressive disorders than in healthy subjects. This is partially due to this group containing women with PME, but mainly due to it containing women with PMDD. The higher percentage of PMDD suggests similarity between PMDD and other depressive disorders. Furthermore, educating healthy Japanese women and women with depressive disorders about premenstrual symptoms and evidence-based treatment for them is necessary.
Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due to the lack of early detection methods and ineffectiveness of therapy for advanced disease. Until more effective screening methods and therapies are developed, chemoprevention strategies are warranted. The hen has a high spontaneous prevalence of ovarian cancer and has been used as a model for studying ovarian cancer chemoprevention. In this study, we used the hen to determine the effect of progestin alone, estrogen alone, or progestin and estrogen in combination (as found in oral contraceptives) on ovarian cancer prevalence. We found that treatment with progestin alone and in combination with estrogen decreased the prevalence of ovarian cancer. A significant risk reduction of 91% was observed in the group treated with progestin alone (risk ratio 0.0909: 95% confidence interval 0.0117-0.704) and an 81% reduction was observed in the group treated with progestin plus estrogen (risk ratio 0.1916: 95% confidence interval 0.043-0.864). Egg production was also significantly reduced in these treatment groups compared to control. We found no effect of progestin, either alone or in combination with estrogen, on apoptosis or proliferation in the ovary, indicating that this is not the likely mechanism responsible for the protective effect of progestin in the hen. Our results support the use of oral contraceptives to prevent ovarian cancer and suggest that ovulation is related to the risk of ovarian cancer in hens and that other factors, such as hormones, more than likely modify this risk.
ovarian cancer; animal models of cancer; hen; oral contraceptives; ovulation
Several forms of depression are unique to women because of their apparent association with changes in gonadal hormones, which in turn modulate neuroregulatory systems associated with mood and behavior. This review examines the evaluation and treatment of depression that occurs premenstrually, postpartum, or in the perimenopause on the basis of current literature. The serotonergic antidepressants consistently show efficacy for severe premenstrual syndromes (PMSs) and premenstrual dysphoric disorder (PMDD), and are the first-line treatment for these disorders. The use of antidepressants for postpartum depression is compromised by concerns for effects in the infants of breast-feeding mothers, but increasing evidence suggests the relative safety of the antidepressant medications, and the risk calculation should be made on an individual basis. Estradiol may be effective for postpartum depression and for moderate-to-severe major depression in the perimenopause. In spite of its frequent use, progesterone is not effective for the mood and behavioral symptoms of PMS/PMDD, postpartum depression, or perimenopausal depressive symptoms.
depression; premenstrual syndrome; postpartum depression; perimenopause; antidepressant; estrogen; gonadal hormone; treatment
The Major Depression Inventory (MDI) is a new, brief, self-report measure for depression based on the DSM-system, which allows clinicians to assess the presence of a depressive disorder according to the DSM-IV, but also to assess the severity of the depressive symptoms.
We examined the sensitivity, specificity, and psychometric qualities of the MDI in a consecutive sample of 258 psychiatric outpatients. Of these patients, 120 had a mood disorder (70 major depression, 49 dysthymia). A total of 139 subjects had a comorbid axis-I diagnosis, and 91 subjects had a comorbid personality disorder.
Crohnbach's alpha of the MDI was a satisfactory 0.89, and the correlation between the MDI and the depression subscale of the SCL-90 was 0.79 (p < .001). Subjects with major depressive disorder (MDD) had a significantly higher MDI score than subjects with anxiety disorders (but no MDD), dysthymias, bipolar, psychotic, other neurotic disorders, and subjects with relational problems. In ROC analysis we found that the area under the curve was 0.68 for the MDI. A good cut-off point for the MDI seems to be 26, with a sensitivity of 0.66, and a specificity of 0.63. The indication of the presence of MDD based on the MDI had a moderate agreement with the diagnosis made by a psychiatrist (kappa: 0.26).
The MDI is an attractive, brief depression inventory, which seems to be a reliable tool for assessing depression in psychiatric outpatients.
Although circulating hormones and inhibitory gamma-aminobutyric acid (GABA)-related factors are known to affect mood, considerable knowledge gaps persist for biological mechanisms underlying the female bias in mood disorders. Here, we combine human and mouse studies to investigate sexual dimorphism in the GABA system in the context of major depressive disorder (MDD) and then use a genetic model to dissect the role of sex-related factors in GABA-related gene expression and anxiety-/depressive-like behaviors in mice. First, using meta-analysis of gene array data in human postmortem brain (N = 51 MDD subjects, 50 controls), we show that the previously reported down-regulation in MDD of somatostatin (SST), a marker of a GABA neuron subtype, is significantly greater in women with MDD. Second, using gene co-expression network analysis in control human subjects (N = 214; two frontal cortex regions) and expression quantitative trait loci mapping (N = 170 subjects), we show that expression of SST and the GABA-synthesizing enzymes glutamate decarboxylase 67 (GAD67) and GAD65 are tightly co-regulated and influenced by X-chromosome genetic polymorphisms. Third, using a rodent genetic model [Four Core Genotypes (FCG) mice], in which genetic and gonadal sex are artificially dissociated (N ≥ 12/group), we show that genetic sex (i.e., X/Y-chromosome) influences both gene expression (lower Sst, Gad67, Gad65 in XY mice) and anxiety-like behaviors (higher in XY mice). This suggests that in an intact male animal, the observed behavior represents the outcomes of male genetic sex increasing and male-like testosterone decreasing anxiety-like behaviors. Gonadal sex was the only factor influencing depressive-like behavior (gonadal males < gonadal females). Collectively, these combined human and mouse studies provide mechanistic insight into sexual dimorphism in mood disorders, and specifically demonstrate an unexpected role of male-like factors (XY genetic sex) on GABA-related genes and anxiety-like behaviors.
GABA; genetic sex; mood; somatostatin; anxiety; depression
Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.
estradiol valerate; dienogest; oral contraception; combination
Heightened publicity about hormonal contraception and thrombosis risk and the publication of new guidelines by the World Health Organization in 2009 and the Centers for Disease Control and Prevention in 2010 addressing this complex issue have led to multidisciplinary discussions on the special issues of adolescents cared for at our pediatric hospital. In this review of the literature and new guidelines, we have outlined our approach to the complex patients referred to our center. The relative risk of thrombosis on combined oral contraception is three- to fivefold, whereas the absolute risk for a healthy adolescent on this therapy is only 0.05% per year. This thrombotic risk is affected by estrogen dose, type of progestin, mechanism of delivery, and length of therapy. Oral progestin-only contraceptives and transdermal estradiol used for hormone replacement carry minimal or no thrombotic risk. Transdermal, vaginal, or intrauterine contraceptives and injectable progestins need further study. A personal history of thrombosis, persistent or inherited thrombophilia, and numerous lifestyle choices also influence thrombotic risk. In this summary of one hospital's approach to hormone therapies and thrombosis risk, we review relative-risk data and discuss the application of absolute risk to individual patient counseling. We outline our approach to challenging patients with a history of thrombosis, known thrombophilia, current anticoagulation, or family history of thrombosis or thrombophilia. Our multidisciplinary group has found that knowledge of the guidelines and individualized management plans have been particularly useful for informing discussions about hormonal and nonhormonal options across varied indications.
contraception; thrombosis; thrombophilia; hormone
Prenatal serotonin reuptake inhibitor (SRI) exposure has been related to adverse newborn neurobehavioral outcomes; however these effects have not been compared to those that may arise from prenatal exposure to maternal major depressive disorder (MDD) without SRI treatment. This study examined potential effects of MDD with and without SRI treatment on newborn neurobehavior.
This was a prospective, naturalistic study. Women were seen at an outpatient research center twice during pregnancy (26–28 and 36–38 weeks gestational age (GA)). Psychiatric diagnoses were assessed using the Structured Clinical Interview for the DSM-IV; medication use was measured with the Timeline Follow-Back instrument. Three groups were established based upon MDD diagnosis and SRI use: Control (N=56), MDD (N=20) or MDD+SRI (N=36). Infants were assessed on a single occasion within 3 weeks of birth with the NICU Network Neurobehavioral Assessment Scale (NNNS). Generalized Linear Modeling was used to examine neurobehavioral outcomes by exposure group and infant age at assessment.
Full-term infants exposed to MDD+SRIs had a lower GA than CON or MDD-exposed infants and, controlling for GA, had lower quality of movement and more central nervous system stress signs. In contrast, MDD-exposed infants had the highest quality of movement scores, while having lower attention scores than CON and MDD+SRI-exposed infants.
MDD+SRI-exposed infants appear to have a different neurobehavioral profile than MDD-exposed infants in the first three weeks after delivery; both groups may have different neurobehavioral profiles with increasing age from birth.
infant; motor quality; central nervous system; depression; pregnancy; treatment
None of the contraceptive methods are fully side-effect free. One of the side effects that commonly causes discontinuation is mood changes and depression. The present study aimed to compare the depression between contraceptive methods including low-dose estrogen (LD) combined pills, condom and intrauterine devices (IUD).
Materials and Methods:
In a cross-sectional study, 216 women were selected through systematic random sampling from 10 health care center sin Isfahan in 2011. Beck Depression Inventory II was used and individual productivity characteristics were asked. Validity and reliability of Beck depression inventory have been repeatedly confirmed in Iran. Content validity the productivity characteristics questionnaire was confirmed and its reliability was measured through Cronbach’s alpha correlation coefficient (calculated as 0.71). ANOVA, covariance analysis and logistic regression were used to analyze the data.
Depression was observed in 47.8% of participants; however, there was no difference between mean score of depression in the users of three contraceptive methods.
The findings of this study showed that depression is not correlated with family planning type and fear of depression should not be an obstacle to choose between these methods. Depression is a multifactor issue. This study showed that type of family planning method in itself cannot be the cause of depression and family planners and consultants should consider this.
Contraceptive methods; depression; family planning; mood; side effects
Premenstrual dysphoric disorder (PMDD), a dysphoric form of premenstrual syndrome, is included as a diagnosis for further study in the DSM-IV-TR (APA, 2000). The present study investigated whether a marker of risk for Major Depressive Disorder (MDD), prefrontal brain asymmetry, also characterizes women with PMDD.
In a sample of 25 college women with PMDD symptomatology and 25 matched controls, resting frontal electroencephalographic (EEG) activity was assessed on four occasions within a two-week span.
Across several frontal sites women with PMDD had relatively less left than right prefrontal brain activity, consistent with a diathesis-stress model for menstrual-related dysphoria.
The findings suggest an overlap in the risk profile for MDD and PMDD.
EEG asymmetry; premenstrual dysphoria; risk; diathesis
It has been suggested that patients with major depressive disorder (MDD) who display pretreatment features suggestive of bipolar disorder or bipolar spectrum features might have poorer treatment outcomes.
To assess the association between bipolar spectrum features and antidepressant treatment outcome in MDD.
Open treatment followed by sequential randomized controlled trials.
Primary and specialty psychiatric outpatient centers in the United States.
Male and female outpatients aged 18 to 75 years with a DSM-IV diagnosis of nonpsychotic MDD who participated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.
Open treatment with citalopram followed by up to 3 sequential next-step treatments.
Main Outcome Measures
Number of treatment levels required to reach protocol-defined remission, as well as failure to return for the postbaseline visit, loss to follow-up, and psychiatric adverse events. For this secondary analysis, putative bipolar spectrum features, including items on the mania and psychosis subscales of the Psychiatric Diagnosis Screening Questionnaire, were examined for association with treatment outcomes.
Of the 4041 subjects who entered the study, 1198 (30.0%) endorsed at least 1 item on the psychosis scale and 1524 (38.1%) described at least 1 recent manic-like/hypomaniclike symptom. Irritability and psychotic-like symptoms at entry were significantly associated with poorer outcomes across up to 4 treatment levels, as were shorter episodes and some neurovegetative symptoms of depression. However, other indicators of bipolar diathesis including recent maniclike symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance.
Self-reported psychoticlike symptoms were common in a community sample of outpatients with MDD and strongly associated with poorer outcomes. Overall, the data do not support the hypothesis that unrecognized bipolar spectrum illness contributes substantially to antidepressant treatment resistance.
Ethinyl estradiol (EE) increases endothelium-dependent vasodilation in young women, but certain progestins paired with EE in combination OCPs have been shown to antagonize the vasodilatory effects of EE. Therefore, the purpose of this study was to investigate how endothelial function, serum biomarkers, and resting blood pressures change across an OCP cycle in women using a monophasic OCP formulation containing the progestin drospirenone.
Twelve women were studied during two hormone phases of their OCP cycle; once at the end of three weeks of active pills (30 mcg EE and 3.0 mg drospirenone), and once at the end of a week of placebo pills (no exogenous hormones).
Endothelium-dependent vasodilation was greater during the active phase compared to the placebo phase (p < 0.001). In contrast, there was no difference in endothelium-independent dilation between hormone phases.
These data suggest that the combination of 30 mcg EE and 3.0 mg drospirenone used in the active phase of this OCP increases endothelium-dependent vasodilation compared to a placebo phase.
progestin; estrogen; vasodilation; birth control pills; drospirenone; blood pressure
Comorbidity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) is associated with higher morbidity including suicidal ideation and behavior. Selective serotonin reuptake inhibitors (SSRIs) are a known treatment for PTSD, MDD and comorbid PTSD and MDD. Since the patients with comorbid MDD and PTSD (PTSD-MDD) are sicker, we hypothesize a poorer response to treatment compared to patients with MDD only. Ninety-six MDD patients were included in the study: 76 with MDD only and 20 with PTSD-MDD. Demographic and clinical parameters at baseline were assessed. We examined clinical parameters before and after 3 months of open SSRI treatment in subjects with PTSD-MDD and compared this group to individuals with MDD only. At baseline, PTSD-MDD patients had higher Hamilton Depression Rating Scale and Buss-Durkee Hostility Scale scores compared with MDD only subjects. There was a significant decrease in scores on the Hamilton Depression Rating Scale, Beck Depression Inventory, Beck Hopelessness Scale, and Beck Scale for Suicidal Ideation after three months of treatment with SSRIs in both groups. The magnitude of improvement in Beck Scale for Suicidal Ideation scores was greater in the PTSD-MDD group compared to the MDD only subjects. Symptoms of depression including suicidal ideation improved in MDD patients with or without comorbid PTSD after 3 months of treatment with SSRIs but improvement in suicidal ideation was greater in the PTSD-MDD group. Our finding has not supported the hypothesis that a response to treatment is poorer in the PTSD-MDD group which may indicate that sicker patients benefit more from treatment.
posttraumatic stress disorder; major depressive disorder; suicidal ideation; selective serotonin reuptake inhibitors