Особенности фармакотерапии у женщин, зарубежные публикации

Категория: Контрацепция 
Май 1st, 2012

J Thromb Thrombolysis. 2010 Nov
The changed ultrastructure of fibrin networks during use of oral contraception
and hormone replacement.
Pretorius E, Oberholzer HM, van der Spuy WJ, Meiring JH.

Contraceptives and hormone replacement have been extensively used since the late 1950s. However, adverse effects are common and include an increased risk of cardiovascular diseases, including thrombo-embolic diseases. Previous research has shown that ultrastructure of fibrin networks may provide great insight regarding the thrombotic potential of patients. The current study investigates the scanning electron microscopy (SEM) ultrastructure of fibrin networks of individuals using oral contraceptive therapy as well as individuals using hormone replacement. We compare micrographs of these two groups with micrographs of young, healthy individuals not using oral contraception. Platelet rich plasma and thrombin was used to prepare the fibrin clots. Here we show that during contraceptive and hormone replacement use, a netted fibrin layer forms. We suggest that oestradiol use causes fibrin network changes and these changes can be seen using SEM technology. These changes may provide further evidence regarding the increased occurrence of thrombotic events during contraceptive and hormone replacement therapy.

Psychoneuroendocrinology. 2009 Jun
Putting a finger on potential predictors of oral contraceptive side effects:
2D:4D and middle-phalangeal hair.
Oinonen KA.

Many women experience emotional or physical side effects when taking oral contraceptives (OCs). Despite the potential impact on women’s health and well-being, there are no valid methods to screen women for their risk of OC side effects. The present paper presents the results of two studies where anthropometric indicators of androgen exposure, 2D:4D and middle-phalangeal hair, were examined for their potential as predictors of OC side effects. In study 1, 2D:4D was associated with women’s reports of a history of: (a) negative mood side effects; (b) discontinuation due to negative mood side effects; (c) specific mood side effects (i.e., crying, sadness, and altered trust in one’s partners) and (d) specific physical side effects (i.e., headaches, fatigue, and decreased sex drive). In study 2, 2D:4D and/or middle-phalangeal hair was/were associated with a reported history of: (a) discontinuation due to negative mood side effects; (b) specific mood-related side effects (i.e., negative mood, disrupted sleep, increased aggression, and altered trust in one’s partner) and (c) specific physical side effects (i.e., headaches, decreased menstrual cramps, and increased sex drive/arousal). The general pattern was that adverse OC side effects were experienced by women with lower 2D:4D and fewer middle-phalangeal hairs. Almost all relationships remained significant when response bias was controlled. These results suggest a possible role for prenatal testosterone exposure and both androgen action and sensitivity in women’s experience of OC side effects. Furthermore, these two digit measures may be useful predictors of hormonal contraceptive side effects in women.

Contraception. 2009 Jan
Prevalence of psychiatric disorders and premenstrual dysphoric symptoms in
patients with experience of adverse mood during treatment with combined oral
contraceptives.
Segebladh B, Borgström A, Odlind V, Bixo M, Sundström-Poromaa I.

BACKGROUND: Negative mood symptoms remain one of the major reasons for discontinuation of combined oral contraceptive pills (COCs). The primary aim of this study was to compare the prevalence of mood and anxiety disorders in women with different experience of COCs.
STUDY DESIGN: Thirty women currently on COCs with no report of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 33 women who had discontinued COC use due to adverse mood effects and 27 women who had discontinued COC use for reasons other than adverse mood symptoms were included. Ongoing psychiatric disorders were evaluated by a structured psychiatric interview and prevalence rates of premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) were assessed by daily prospective ratings on the Cyclicity Diagnoser scale.
RESULTS: Women with ongoing or past experience of COC-induced adverse mood, more often suffered from mood disorders than women with no reports of adverse mood while on COC. The prevalence of prospectively defined PMS or PMDD did not differ between prior users with positive or negative experience. Women who had discontinued COC use due to adverse mood symptoms more often had had a legal abortion in the past.
CONCLUSION: Women with ongoing or past self-reported adverse mood effects from
COCs had a significantly increased prevalence of mood disorders.

Curr Opin Pediatr. 2008 Aug
Controversies in contraception.
Department of Medicine, Children’s Hospital Boston, Harvard Medical School,
Boston, Massachusetts 02115, USA. sarah.pitts@childrens.harvard.edu

PURPOSE OF REVIEW: New research is constantly being published regarding hormonal contraceptives and bone health, migraine headaches, thrombosis risk, hypertension, weight gain, and obesity, as well as emergency contraception. At times, these studies can be clarifying, but they can also raise new controversies and questions. It is important for providers to be aware of the emerging issues regarding contraceptive care for adolescent patients.
RECENT FINDINGS: Research suggests that Depo-Provera (depot medroxyprogesterone
acetate; Pfizer, New York City, New York, USA) and, perhaps, low-dose oral contraceptive pills can have adverse effects on adolescent bone health, although the data demonstrating reversibility of bone loss after discontinuation of these contraceptives are reassuring. Additionally, estrogen-containing contraceptives pose risks for patients, including the onset of or exacerbation of migraine headaches, venous thromboembolism, and hypertension. Depo-Provera has been
implicated in weight gain, especially in girls who are already overweight. Obesity may decrease the efficacy of some hormonal contraceptives. Finally, the mechanism of action of emergency contraception is still unknown, although studies continue to suggest that it has primarily preovulatory, not postovulatory, effects.
SUMMARY: Adolescent health providers need to be aware of the new research and
controversies in contraceptive care in order to counsel and care for patients effectively.

Obstet Gynecol. 2008 Feb
Effects of oral and transdermal hormonal contraception on vascular risk markers:
a randomized controlled trial.
Department of Obstetrics and Gynecology, University of Vermont, Burlington,
Vermont 0450, USA. Julia.Johnson@vtmednet.org

OBJECTIVE: To compare the effects of oral and transdermal contraceptives containing similar hormone formulations on vascular risk markers.
METHODS: We conducted a randomized, investigator-blinded, crossover, clinical trial with 24 healthy women, aged 18-35 years, who received 2 months of transdermal or oral contraceptive, 2 months washout, then 2 months of the alternative medication. The transdermal contraceptive contained 0.75 mg ethinyl estradiol and 6 mg norelgestromin. The oral contraceptive contained 35 mcg ethinyl estradiol and 250 mcg norgestimate. Blood samples taken before and after each treatment were analyzed in batch for D-dimer, von Willebrand factor, factor VIII, total and free protein S, antithrombin, fibrinogen, C-reactive protein, and normalized activated protein C sensitivity ratio (nAPCsr) determined with two thrombin generation-based assays, the alpha2macroglobulin-thrombin end point method (alpha2M-IIa) and calibrated automated thrombinography. Repeated measures analysis of variance was used for analysis.
RESULTS: For both contraceptives (transdermal, oral) there were significant declines in free (19%, 11%) and total protein S (19%, 13%) and antithrombin (13%,10%); increases in fibrinogen (8%, 10%), C-reactive protein (220%, 292%), nAPCsr alpha2M-IIa (81%, 61%), and nAPCsr calibrated automated thrombinography (102%, 68%), all P<.05. Transdermal contraceptives had a greater effect than oral contraceptives on free protein S (P=.07), nAPCsr alpha2M-IIa (P=.06), and nAPCsr calibrated automated thrombinography (P=.03).
CONCLUSION: Oral and transdermal contraception with similar hormones had similar adverse effects on vascular risk markers. This suggests that this transdermal contraceptive has at least a similar thrombosis risk as its oral counterpart.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00554632
LEVEL OF EVIDENCE: I.

South Med J. 2007 Sep
An unusual cause of cerebral venous sinus thrombosis: prothrombin G20210A gene
mutation.
Porres-Aguilar M, Square JH, Storey R, Rodriguez-Dunn S, Mohamed-Aly MS.

Cerebral venous sinus thrombosis represents less than 1% of all strokes, being an uncommon entity with a wide spectrum of clinical scenarios. We present a 45-year-old Hispanic female with a history of long-term oral contraceptive use who was diagnosed with cerebral venous sinus thrombosis due to a heterozygous carrier mutation in the prothrombin G20210A gene. The patient was successfully managed with intravenous heparin with favorable clinical results without adverse effects. The prevalence of inherited primary thrombophilia increases with
additional risk factors such as the use of oral contraceptives that can trigger or prothrombotic events in any vascular bed. An increased prevalence in the prothrombin G20210 gene mutation has been demonstrated in the Mexican-Mestizo population. Controversy exists regarding therapy of cerebral venous sinus thrombosis; according to experts, heparin remains the cornerstone of therapy with acceptable outcomes. More clinical trials are required to evaluate long-term outcomes in this subgroup of patients.

Semin Vasc Med. 2003 Feb
Venous and arterial thrombosis during oral contraceptive use: risks and risk
factors.
Tanis BC, Rosendaal FR.

Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two-to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 microg to 20-30 microg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis.

W V Med J. 2011 Sep-Oct
Case of ischemic colitis in a young adolescent associated with triphasic hormonal
contraceptive therapy: a case report and review of the literature.
Rasmussen DK, Segars LW.

There has been speculation that third generation hormonal contraceptives may be less prone to inducing clotting than the earlier generation products. We present a case of colonic ischemia in a young adolescent receiving pharmacotherapy with a third-generation hormonal contraceptive. Ischemic colitis is an uncommon adverse effect in young adolescents associated with hormonal contraception, especially the third generation agents. We believe this case to be the second-youngest patient reported with ischemic colitis due to this therapy. Clinical vigilance is recommended for women presenting with abdominal pain, with or without hematochezia, who are receiving hormonal contraceptive therapy. Since their introduction in the early 1960′s, the combination hormonal contraceptives have been utilized by millions of women for both contraceptive and non-contraceptive purposes. Although a variety of adverse effects can be experienced by individuals taking these agents, it has been demonstrated that these agents are associated with an increased risk of venous and arterial thromboses. Publications more consistently report on the cardiovascular-, pulmonary-, peripheral vascular-, or cerebrovascular-based thrombotic events associated with these agents. During the past several decades changes have been incorporated in the dose and types of compounds included in the combination ormonal contraceptive products in an attempt to reduce the risk of coagulation and other adverse effects. Less common and less frequently publicized are the gastrointestinal-based thrombotic eventsthat result in ischemia and presents as severe abdominal pain, with or without hematochezia. We report an uncommon case of reversible colonic ischemia in who we believe to be the second-youngest adolescent female reported in the literature (youngest aged 16 years) to have this diagnosis associated with the use of a newer, third-generation oral combination hormonal contraceptive (Naranjo scale of 7; Probable).

Neuroscience. 2011 Sep 15
Paradoxical effects of GABA-A modulators may explain sex steroid induced negative
mood symptoms in some persons.
Bäckström T, Haage D, Löfgren M, Johansson IM, Strömberg J, Nyberg S, Andréen L,
Ossewaarde L, van Wingen GA, Turkmen S, Bengtsson SK.

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

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