CONTRACEPTIVES HORMONAL [keywords]
- [Pharmacokinetic and pharmacodynamic effects of psychotropic medications: Differences between sexes]. [JOURNAL ARTICLE, ENGLISH ABSTRACT]
- Psychiatriki 2016 Apr-Jun; 27(2):118-126.
The gender based or gender sensitive pharmacology is a new research area. Differences among sexes are observed in several parameters of their pharmacokinetic which may relate to alteration of their pharmacodynamic as well. Most psychotropics are given per os, and the greater part of their absorption takes place in the small intestine. Premenopausal women have slower gastric emptying times and lower gastrointestinal blood flow which probably reduces the extent of drug absorption. The distribution of drugs is influenced by the relative lower body mass index, the lower blood volume and flow and the greater percentage of body fat of women. Further, the elimination and renal clearance is reduced in women and the hepatic metabolism differ between sexes. Besides, women differ from men in physiological conditions which may have an impact on the psychotropic medication and dosage required for efficacy and response. Women are exposed to monthly hormonal fluctuations (menstruation), pregnancy, puerperium, menopause and use of contraceptives or synthetic hormonal replacement therapies. Throughout of these conditions changes may occur in total body water, in renal clearance, cardiovascular and autoimmune system, which may cause fluctuations in the activity of the psychotropics, changes in the central neurotransmitters, in the number and sensitivity of the receptors, and the general metabolism as well. Despite the fact that women are the primer consumers of psychotropic medication, taking more psychotropics as well as more multiple medications than men, little attention has been paid to sex differences in psychopharmacology. Till recently women were under-represented or excluded from most of the pharmacological clinical trials. The treatment guidelines for psychotropic medication are based on studies verified and investigated almost exclusively in men. Results from such studies were generalized and recommended for use in the clinical practice without any critique and justification between the sexes. In conclusion, women compared to men, tend to have a greater bioavailability and slower elimination of drugs leading to higher concentrations of free circulating drugs in serum and causing more side effects and adverse reactions to the psychotropic medication than men do. In general, women require lower doses of antidepressants, antipsychotics and benzodiazepines than men. For safety and efficacy reasons and despite the fact that research is still being carried out to determine the exact differences in pharmacodynamic of several psychotropics between genders, the clinician must be aware of the reported effect of the recommended medications on serum levels and organ tissues both for men and women.
- Drug Interactions between Hormonal Contraceptives and Psychotropic Drugs: A Systematic Review. [REVIEW, JOURNAL ARTICLE]
- Contraception 2016 Jul 18.
To examine whether the co-administration of hormonal contraceptives (HC) and psychotropic drugs commonly used to treat anxiety and/or depression results in safety or efficacy concerns for either drug.We searched PubMed and Cochrane libraries for clinical or pharmacokinetic [PK] studies that examined co-administration of any HC with psychotropic drugs (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], oral benzodiazepines, bupropion, mirtazapine, trazadone, buspirone, hydroxyzine, monoamine oxidase inhibitors [MAOIs], or atypical antipsychotics) in reproductive aged women.Of 555 articles identified, 22 articles (18 studies) met inclusion criteria. We identified five studies on SSRIs, four on TCAs, one on bupropion, three on atypical antipsychotics and five on oral benzodiazepines. No articles met inclusion criteria for SNRIs, mirtazapine, trazadone, buspirone, hydroxyzine or MAOIs. Overall, clinical studies did not demonstrate differences in unintended pregnancy rates when HCs were administered with and without psychotropic drugs or in psychotropic drug treatment outcomes when psychotropic drugs were administered with and without HCs. PK studies did not demonstrate changes in drug exposure related to contraceptive safety, contraceptive effectiveness or psychotropic drug effectiveness for most classes of psychotropic drugs. However, limited PK data raise concern for HCs increasing systemic exposure of amitriptyline and imipramine (both TCAs), theoretically posing safety concerns.Limited quality and quantity evidence on use of psychotropic drugs and HCs suggests low concern for clinically significant interactions, though no data exist specifically for non-oral formulations of HC. Given the high frequency of use for both HCs and psychotropic drugs among reproductive age women in the US, this review highlights a need for further research in this area.
- Co-Administration of St. John's Wort and Hormonal Contraceptives: A Systematic Review. [REVIEW, JOURNAL ARTICLE]
- Contraception 2016 Jul 18.
St. John's wort (SJW) is a known strong inducer of the cytochrome P450 (CYP) 3 A4 enzyme, and both the ethinyl estradiol and progestin components of hormonal contraceptives are substrates of CYP3A4. This systematic review examined whether the co-administration of SJW and hormonal contraceptives leads to significant safety or efficacy concerns.Systematic review.PubMed and Cochrane Library databases were searched for articles of any comparative study design (clinical or pharmacokinetic) that examined potential interactions between SJW and hormonal contraceptives in women of reproductive age.Of the 48 identified articles, four studies met inclusion criteria and compared use of combined oral contraceptives (COCs) alone to the use of COCs co-administered with SJW. Two studies demonstrated no change in markers of ovulation, but one study demonstrated increased follicular growth and probable ovulation when COCs were co-administered with SJW. Three studies demonstrated an increased risk of breakthrough bleeding with COCs and SJW. Three studies showed changes in at least one pharmacokinetic parameter that suggested a significantly decreased exposure to hormone concentrations when COCs were co-administered with SJW. The only study that did not demonstrate any significant pharmacokinetic differences examined a SJW product containing a low amount of hypericin.Limited evidence showing increased risk of ovulation and breakthrough bleeding raises concern for decreased contraceptive efficacy when COCs are co-administered with SJW. The pharmacokinetic evidence is mixed but suggests that SJW administration may be associated with weak to moderate induction of the metabolism of COCs.
- Impact of Contraceptive Type on Sexual Desire of Women and of Men Partnered to Contraceptive Users. [JOURNAL ARTICLE]
- J Sex Med 2016 Jul 22.
Research investigating the impact of contraceptive use on sexual desire has produced mixed results. This scholarship also has had inconsistent methodology, with some studies not separating contraceptive types and others lacking non-hormonal comparison groups. Relationship context of contraceptive use and sexual behavior also have not been well represented.To investigate the impact of contraceptive type on sexual desire in women and in men who are partnered to contraceptive-using women.In two separate studies we examined the impact of contraceptives on the sexual desire of women currently using contraceptives and men partnered to women using contraceptives. The first study examined the impact of contraceptive type on sexual desire in women and in men partnered to contraceptive users in relationships of different lengths. The second study examined this impact in heterosexual couples in long-term relationships.Solitary and dyadic sexual desire as measured by the Sexual Desire Inventory and contraceptive type as categorized into three types: oral hormonal contraceptive, other hormonal contraceptive, and non-hormonal contraceptive.Contraceptive type significantly affected solitary and dyadic desire. Women on non-hormonal contraceptives reported higher solitary sexual desire than women on other hormonal contraceptives. Women on oral hormonal contraceptives reported significantly higher dyadic sexual desire than women on non-hormonal contraceptives. In male partners of female contraceptive users, solitary and dyadic sexual desires were not affected by partner contraceptive type. In the multivariate model, relationship length and age were stronger predictors of contraceptive type than was solitary or dyadic sexual desire. At the couple level, contraceptive type also was not related to solitary or dyadic sexual desire in men and women.Contraceptive type can affect solitary and dyadic sexual desire in women; however, contextual factors seem to be stronger predictors of sexual desire for long-term coupled women and men than contraception type.
- Contraceptive use among women with multiple sclerosis: A systematic review. [REVIEW, JOURNAL ARTICLE]
- Contraception 2016 Jul 21.
Contraception is an important consideration for women with multiple sclerosis (MS), however little is known about the possible effects of hormonal contraception on disease progression or other adverse outcomes (e.g., thrombosis, low bone mineral density).To evaluate the evidence on the safety of contraceptive use among women with MS.We searched the PubMed database for peer-reviewed articles published in any language from database inception through July 2015.We included studies that examined health outcomes among women diagnosed with MS initiating or continuing a contraceptive method. We excluded case reports and case series but included all other study designs.From 111 articles, we identified four studies (from 5 articles) that met our inclusion criteria. Evidence from one randomized controlled trial, two retrospective cohort studies, and one cross-sectional study suggests that use of combined oral contraceptives or oral contraceptives (type not specified) among women with MS does not worsen the clinical course of disease, defined as disability level, disease severity or progression, relapse, or number of new brain lesions on magnetic resonance imaging (body of evidence grading Level I, fair to Level II-3, poor). No studies were identified that examined the safety of other contraceptive methods or examined other outcomes of interest (venous thromboembolism, changes in bone mineral density) related to contraceptive use among women with MS.Limited evidence suggests that COC or OC use after MS onset does not worsen the clinical course of disease.
- Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices. [Journal Article, Review]
- J Int AIDS Soc 2016; 19(3 Suppl 2):20810.
Studies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW worldwide. After receiving a diagnosis, HIV-positive TGW have challenges accessing effective HIV treatment, as demonstrated by lower rates of virologic suppression and higher HIV-related mortality. These adverse HIV outcomes have been attributed to the multiple sociocultural and structural barriers that negatively affect their engagement within the HIV care continuum. Guidelines for feminizing hormonal therapy among TGW recommend combinations of oestrogens and androgen blockers. Pharmacokinetic studies have shown that certain antiretroviral therapy (ART) agents, such as protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and cobicistat, interact with ethinyl estradiol, the key oestrogen component of oral contraceptives (OCPs). The goal of this article is to provide an overview of hormonal regimens used by TGW, to summarize the known drug-drug interactions (DDIs) between feminizing hormonal regimens and ART, and to provide clinical care recommendations.The authors identified English language articles examining DDIs between oestrogen therapy, androgen blockers and ART published between 1995 and 2015 using PubMed, Cumulative Index to Nursing and Allied Health Literature and EBSCOhost.Published articles predominantly addressed interactions between ethinyl estradiol and NNRTIs and PIs. No studies examined interactions between ART and the types and doses of oestrogens found in feminizing regimens. DDIs that may have the potential to result in loss of virologic suppression included ethinyl estradiol and amprenavir, unboosted fosamprenavir and stavudine. No clinically significant DDIs were noted with other anti-retroviral agents or androgen blockers.There are insufficient data to address DDIs between ART and feminizing hormone regimens used by TGW. There is an urgent need for further research in this area, specifically pharmacokinetic studies to study the direction and degree of interactions between oral, injectable and transdermal estradiol and ART. Clinicians need to be vigilant about possible interactions and monitor hormone levels if concerns arise. More research is also needed on the provision of hormone therapy and gender-affirming care on the long-term health outcomes of HIV-positive TGW.
- Environmental exposures and the development of systemic lupus erythematosus. [JOURNAL ARTICLE]
- Curr Opin Rheumatol 2016 Jul 13.
This review examines evidence relating environmental factors to the development of systemic lupus erythematosus (SLE).The strongest epidemiologic evidence exists for the associations of silica, cigarette smoking, oral contraceptives, postmenopausal hormone therapy and endometriosis, with SLE incidence. Recent studies have also provided robust evidence of the association between alcohol consumption and decreased SLE risk. There are preliminary, conflicting or unsubstantiated data that other factors, including air pollution, ultraviolet light, infections, vaccinations, solvents, pesticides and heavy metals such as mercury, are related to SLE risk. Biologic mechanisms linking environmental exposures and SLE risk include increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal triggers, as well as epigenetic modifications resulting from exposure that could lead to SLE.Identifying the environmental risk factors related to risk of SLE is essential as it will lead to increased understanding of pathogenesis of this complex disease and will also make risk factor modification possible for those at increased risk.
- Genetic, hormonal and metabolic aspects of PCOS: an update. [Journal Article, Review]
- Reprod Biol Endocrinol 2016; 14(1):38.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.
- Safety of Intrauterine Devices in Breastfeeding Women: A Systematic Review. [REVIEW, JOURNAL ARTICLE]
- Contraception 2016 Jul 12.
To investigate levonorgestrel (LNG)-releasing and copper-bearing (Cu) intrauterine device (IUD) safety among breastfeeding women and, for Cu-IUD use, breastfeeding performance and infant health.Systematic review METHODS: We searched PubMed, Embase, Cochrane Library and clinicaltrials.gov for articles through January 2016. We included studies of Cu-IUD or LNG-IUD users comparing IUD-specific (perforation, expulsion) and other contraceptive-related (infection, removal/cessation due to bleeding/pain, and other adverse events) outcomes for breastfeeding versus non-breastfeeding women. We also included studies of breastfeeding women comparing contraceptive-related outcome for IUD-users versus other contraceptive-method users. Finally, we included studies comparing breastfeeding outcomes among Cu-IUD users to users of other non-hormonal contraceptives or no contraception.Of 548 articles identified, 23 (16 studies) met inclusion criteria. Two studies suggested the risk of IUD perforation was 6-10 times higher among breastfeeding versus non-breastfeeding women. Seven studies suggested risks for other adverse events were similar or lower among breastfeeding versus non-breastfeeding women. Three studies among breastfeeding women found no increased risk of adverse events in IUD users versus non-users. Breastfeeding performance and infant growth were similar for Cu-IUD users and users of other non-hormonal methods or no contraception.Overall, risks for adverse events among IUD users, including expulsion, pain and removals were similar or lower for breastfeeding women versus non-breastfeeding women. Uterine perforation with IUDs, while rare, appeared more frequent among breastfeeding women. No evidence indicated Cu-IUD use in breastfeeding women influences breastfeeding performance or infant growth.
- Diagnosis and Treatment of Polycystic Ovary Syndrome. [Journal Article]
- Am Fam Physician 2016 Jul 15; 94(2):106-13.
Polycystic ovary syndrome is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Although the pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. Metabolic syndrome is twice as common in patients with polycystic ovary syndrome compared with the general population, and patients with polycystic ovary syndrome are four times more likely than the general population to develop type 2 diabetes mellitus. Patient presentation is variable, ranging from asymptomatic to having multiple gynecologic, dermatologic, or metabolic manifestations. Guidelines from the Endocrine Society recommend using the Rotterdam criteria for diagnosis, which mandate the presence of two of the following three findings- hyperandrogenism, ovulatory dysfunction, and polycystic ovaries-plus the exclusion of other diagnoses that could result in hyperandrogenism or ovulatory dysfunction. It is reasonable to delay evaluation for polycystic ovary syndrome in adolescent patients until two years after menarche. For this age group, it is also recommended that all three Rotterdam criteria be met before the diagnosis is made. Patients who have marked virilization or rapid onset of symptoms require immediate evaluation for a potential androgen-secreting tumor. Treatment of polycystic ovary syndrome is individualized based on the patient's presentation and desire for pregnancy. For patients who are overweight, weight loss is recommended. Clomiphene and letrozole are first-line medications for infertility. Metformin is the first-line medication for metabolic manifestations, such as hyperglycemia. Hormonal contraceptives are first-line therapy for irregular menses and dermatologic manifestations.