An oocyte donation protocol using the GnRH antagonist ganirelix acetate, does not compromise embryo quality and is associated with high pregnancy rates.

PURPOSE: To evaluate the effect of the GnRH antagonist, ganirelix acetate, on oocyte quality. METHODS: Stimulation characteristics, implantation rates and clinical pregnancy rates were compared between 29 oocyte donors 21-31 years of age who underwent 31 cycles of ovarian stimulation with gonadotropins and ganirelix acetate, and 36 infertile couples of similar age range who underwent 51 cycles of ovarian stimulation using the same protocol. RESULTS: A significantly lower number of embryos were transferred in the donor/recipient group as compared to the infertile group (2.32+/-0.54 vs. 2.82+/-0.71, P<0.05). In contrast, implantation and clinical pregnancy rates per transfer, were significantly higher in the donor/recipient group (38.1% vs. 10.4%, P<0.01) and (61.3% vs. 23.1%, P<0.05) respectively, as compared to the infertile group. CONCLUSIONS: Incorporation of ganirelix acetate for pituitary suppression in stimulation protocols for oocyte donation is associated with high pregnancy rates suggesting that ganirelix acetate does not exert an adverse effect on oocyte or embryo quality.

Prolactin receptor gene expression and immunolocalization of the prolactin receptor in human luteinized granulosa cells.

Prolactin is mainly known for its role in breast development and lactation, but has been also implicated in other physiological functions such as immunoregulation and ovarian steroid production. Although prolactin and prolactin receptor (PRL-R) transcripts have been previously identified in the human ovary, the spatial localization of the receptor is unknown. To investigate the presence of PRL-R within the follicular apparatus, human luteinized granulosa cells were obtained at the time of follicular aspiration from women undergoing ovarian stimulation for IVF. RNA extracted from these cells was subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the PRL-R gene. In addition, paraffin sections of isolated granulosa cells and sections of premenopausal human ovaries were immunostained with a mouse anti-human PRL-R monoclonal antibody. PRL-R were immunolocalized to the cell membrane of isolated luteinized granulosa cells and PRL-R transcripts were detected in the extracted RNA. No detectable staining was noted in secondary and early antral follicles in archived paraffin sections. These findings confirm the presence of PRL-R in human luteinized granulosa cells and suggest a localized role for PRL within the mature follicle. The absence of PRL-R in the early follicle suggests that the effects of prolactin are exerted around the time of ovulation.

Adrenocortical secretion of dehydroepiandrosterone in healthy women: highly variable response to adrenocorticotropin.

Excess adrenal androgen (AA) levels are observed in 25--50% of women with the polycystic ovary syndrome (PCOS), and AA excess in PCOS may represent selection bias. Thus, it is possible that AA secretion among the general population is highly variable, and that those women who are predisposed to secreting greater amounts of AA have a greater probability of having PCOS. We now hypothesize that the levels of AAs are highly variable among normal nonhyperandrogenic women, and that this heterogeneity is the result of a variable response of AAs to ACTH stimulation. To test this hypothesis we prospectively studied the response of dehydroepiandrosterone (DHA) and cortisol (F) to a 60-min acute stimulation with ACTH-(1--24) in 56 healthy eumenorrheic nonhirsute healthy women with a mean age of 28.9 yr (range, 20--37 yr.) and a mean body mass index (BMI) of 29.2 kg/m(2) (18.2--46.2 kg/m(2)). Baseline samples and poststimulation samples were assayed for DHA and F. The basal and ACTH-stimulated levels of DHA, but not those of F, were negatively correlated with age, although neither the basal nor ACTH-stimulated responses of DHA and F varied with BMI. After controlling for age, the basal F level was negatively correlated to its net increment (i.e. Delta F; r = -0.54; P < 0.001), whereas there was no significant relationship between basal DHA and Delta DHA. We also compared the intersubject variability (coefficient of variation) for basal and stimulated levels of DHA and F. For basal (DHA(0)), 60 min (DHA(60)), and net increment in (Delta DHA) DHA levels, the coefficients of variation were 67.9%, 61.4%, and 76.0%, respectively; for F(0), F(60), and Delta F, they were 40.4%, 16.9%, and 31.3%, respectively. The variance in Delta DHA was significantly higher, and the variance in F(60) was significantly lower than that in all other variables; DHA(0), DHA(60), F(0), and Delta F had similar variances. In conclusion, in our population of healthy reproductive-aged women we observed that both basal and ACTH-stimulated levels of DHA after ACTH-(1--24) stimulation had significantly greater intersubject variance (approximately 60--70%) compared with the basal and poststimulation levels of F (approximately 15--40%). These data support the hypothesis that among normal women, AA (i.e. DHA) levels are highly variable compared to those of F. In addition, the intersubject variability in DHA levels is at least in part due to a variable response of AAs to ACTH stimulation. Whether the AA excess frequently observed in PCOS is due to the greater risk of those women with higher AA levels, basally and after ACTH stimulation, remains to be confirmed.

Polycystic ovary syndrome, hyperandrogenism, and insulin resistance.

Results from recent basic and clinical research investigations have greatly improved our understanding of insulin resistance in general and insulin resistance associated with PCOS in particular. With this understanding has come the possibility of using new methods to treat PCOS. This is particularly true when discussing the use of insulin-sensitizing drugs. Caution must be exercised in using these drugs because of unforeseen acute or remote adverse side effects. Postulated relationships among PCOS, hyperandrogenism, and insulin resistance do not completely solve the endocrinologic mystery of the patient with PCOS. For example, how does the partial destruction of the ovary (e.g., wedge biopsy or ovary drilling by laser or cautery), which does not affect insulin resistance, result in ovulatory cycles? Why does the administration of excessive exogenous insulin in the case of the insulin-dependent diabetic fail to cause hyperandrogenism? Certainly, much remains to be learned about the reproductive endocrine disturbance we now call PCOS.

Polycystic ovary syndrome and hyperprolactinemia.

Analysis of the evidence linking PCOS and hyperprolactinemia suggests that these conditions have independent origins. Elevated prolactin serum levels are documented in the early studies of patients with polycystic ovaries. However, recent investigators using serial serum sampling have excluded transient elevations of prolactin and have shown a less frequent association of these disorders. Treatment of individuals with both PCOS and hyperprolactinemia is distinct from the management of the individual with only one of these conditions. Upon evaluating the therapeutic alternatives for dysfunctional uterine bleeding and hirsutism in these patients, the effect of exogenous estrogen and progesterone on the secretion of prolactin must be considered. The addition of a dopamine agonist (e.g., bromocriptine or cabergoline) to a regimen of clomiphene citrate must also be considered as ovulation induction options for these women. Finally, future discoveries about the relationship between PCOS and hyperprolactinemia will require a better understanding of how the hypothalamus regulates the pituitary secretion of LH and prolactin.

Exogenous luteinizing hormone (LH) increases estradiol response patterns in poor responders with low serum LH concentrations.

PURPOSE: Our purpose was to investigate whether the addition of exogenous leuteinizing hormone (LH) increases estradiol secretion in LH-depleted women undergoing controlled ovarian hyperstimulation (COH) with purified follicle stimulating hormone (FSH). METHODS: We carried out case series and retrospective analysis of midfollicular serum LH concentrations and estradiol response patterns in COH cycles. All patients initially received gonadotropins containing purified FSH. Human menopausal gonadotropin containing LH was added to poor responders with low midfollicular LH concentrations. RESULTS: The addition of exogenous LH to the COH regimen significantly increased estradiol secretion in poor responders with low midfollicular endogenous LH concentrations. This was confirmed statistically by an average change in the slope of the estradiol patterns from 27.54 to 85.49 after the addition of exogenous LH. Furthermore, patients with midfollicular serum LH concentrations < 3.0 mIU/ml had significantly lower midfollicular and peak estradiol (E2) concentrations compared to patients with LH concentrations > or = 3.0 mIU/ml (352.3 and 2094.3 vs 855.6 and 3757.1 pg/ml, respectively). CONCLUSIONS: The addition of exogenous LH increases E2 response patterns in poor responders with low midfollicular serum LH concentrations. Low midfollicular serum LH concentrations are associated with significantly lower midfollicular and peak E2 concentrations.

The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive.

BACKGROUND: Rifampin (INN, rifampicin), a CYP34A inducer, results in significant interactions when coadministered with combination oral contraceptives that contain norethindrone (INN, norethisterone) and ethinyl estradiol (INN, ethinylestradiol). Little is known about the effects of rifabutin, a related rifamycin. OBJECTIVES AND METHODS: The relative effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone were evaluated in a prospective, randomized, double-blinded crossover study in 12 premenopausal women who were on a stable oral contraceptive regimen that contained 35 microg ethinyl estradiol/1 mg norethindrone. Subjects were randomized to receive 14 days of rifampin or rifabutin from days 7 through 21 of their menstrual cycle. After a 1-month washout period (only the oral contraceptives were taken), subjects were crossed over to the other rifamycin. RESULTS: Rifampin significantly decreased the mean area under the plasma concentration-time curve from time 0 to 24 hours [AUC(0-24)] of ethinyl estradiol and the mean AUC(0-24) of norethindrone. Rifabutin significantly decreased the mean AUC(0-24) of ethinyl estradiol and the mean AUC(0-24) of norethindrone. The effect of rifampin was significantly greater than rifabutin on each AUC(0-24). Despite these changes, subjects did not ovulate (as determined by progesterone concentrations) during the cycle in which either rifamycin was administered. Levels of mean follicle-stimulating hormone increased 69% after rifampin. CONCLUSION: In this study, rifampin (600 mg daily) was a more significant inducer of ethinyl estradiol and norethindrone clearance than rifabutin (300 mg daily), but neither agent reversed the suppression of ovulation caused by oral contraceptives. The carefully monitored oral contraceptive administration and the limited exposure to rifamycins may restrict the application of this study to clinical situations.

PIP: The relative effects of rifampin and rifabutin (a related rifamycin) on the pharmacokinetics and pharmacodynamics of ethinyl estradiol (EE) and norethindrone were evaluated in a prospective, randomized, double-blinded crossover study in 12 premenopausal women who were on a stable oral contraceptive regimen that contained 35 mcg EE and 1 mg norethindrone. Subjects were randomized to receive 14 days of rifampin or rifabutin from days 7 through 21 of their menstrual cycle. After a 1-month washout period (only the oral contraceptives were taken), subjects were crossed over to the other rifamycin. Findings showed that rifampin significantly decreased the mean area under the plasma concentration-time curve from time 0 to 24 hours [AUC (0-24)] of EE and the mean AUC (0-24) of norethindrone. Rifabutin significantly decreased the mean AUC (0-24) of EE and the mean AUC (0-24) of norethindrone. The effect of rifampin was significantly greater than rifabutin on each AUC (0-24). Despite these changes, subjects did not ovulate (as determined by progesterone concentrations) during the cycle in which either rifamycin was administered. Levels of mean follicle-stimulating hormone increased 69% after rifampin. This study suggests that rifampin (600 mg daily) was a more important inducer of EE and norethindrone clearance than rifabutin, but none of these agents were able to reverse the suppression of ovulation done by oral contraceptives.

Indications for surgery in the treatment of hyperprolactinemia.

Indications for pituitary surgery have been described in the medical literature, but they do not necessarily apply to prolactin-secreting (PRL-secreting) pituitary microadenomas or macroadenomas. Reviews of pituitary surgery done for microprolactinomas and macroprolactinomas have not demonstrated any significant beneficial effect on the clinical course of the hyperprolactinemia. At the same time, such surgery has been associated with definite risks, including an overall mortality of 0.9%. There is even the possibility that surgery and radiation for benign pituitary adenomas can facilitate malignant transformation and metastasis. Therefore, medical treatment with a dopamine agonist is the primary choice for all PRL-secreting microadenomas and macroadenomas. Referral for surgical evaluation is reserved for patients in whom neurologic deficits, such as visual field impairment or cranial nerve deficits, do not improve with medical therapy and for certain other, rare situations.

Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase.

BACKGROUND: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). MATERIALS AND METHODS: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alternations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. RESULTS: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. CONCLUSIONS: The reproductive deficits in nNOS-/- females are most likely due to alternations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.

Brain opioid receptor measurements by positron emission tomography in normal cycling women: relationship to luteinizing hormone pulsatility and gonadal steroid hormones.

The regulation of central mu-opioid receptors in women during the menstrual cycle was explored with positron emission tomography and the selective radiotracer [11C]carfentanil. Ten healthy women were studied twice, during their follicular and luteal phases. Plasma concentrations of estradiol, progesterone, testosterone, and beta-endorphin were determined immediately before scanning. LH pulsatility was measured over the 9 h preceding each of the two positron emission tomography scans. No significant differences in the binding potential of mu-opioid receptors (binding capacity/Kd) were observed between phases of the menstrual cycle. However, significant negative correlations were observed between circulating levels of estradiol during the follicular phase and mu-receptor binding measures in the amygdala and hypothalamus, two regions thought to be involved in the regulation of GnRH pulsatility. LH pulse amplitude was positively correlated with mu binding in the amygdala, whereas LH pulse number was negatively correlated with binding in this same region. No significant associations were noted between LH pulse measures and the hypothalamus for this sample. These results suggest that amygdalar mu-opioid receptors exert a modulatory effect on GnRH pulsatility, and that circulating levels of estradiol also regulate central mu-opioid function.

Day 4 estradiol levels predict pregnancy success in women undergoing controlled ovarian hyperstimulation for IVF.

OBJECTIVE: To evaluate the usefulness of serum estradiol levels obtained on the fourth day of gonadotropin stimulation in predicting the likelihood of pregnancy during controlled ovarian hyperstimulation (COH) using luteal phase leuprolide acetate (LA). DESIGN: A 4-year retrospective analysis of day 4 estradiol levels and subsequent clinical pregnancy and delivery rates. SETTING: A university hospital tertiary referral center. PATIENT(S): Couples undergoing IVF treatment. MAIN OUTCOME MEASURE(S): Primary outcome measures included clinical pregnancy and delivery rates. Secondary outcome measures included the number of oocytes retrieved and the number of embryos available for transfer per COH cycle. RESULT(S): The clinical pregnancy and delivery rates for cycles with day 4 estradiol levels of >75 pg/mL were 42.3% (30/71) and 32.4% (23/71), respectively. These rates differed significantly from those for cycles with day 4 estradiol levels of < or = 75 pg/mL, which were only 9.1% (4/44) and 6.8% (3/44), respectively. The number of oocytes retrieved and the number of embryos available for transfer for cycles with day 4 estradiol levels of >75 pg/mL also differed significantly from those for cycles with day 4 estradiol levels of < or = 75 pg/mL (11.4 and 7.8 versus 6.8 and 4.3, respectively). CONCLUSION(S): Estradiol levels obtained on the fourth day of gonadotropin therapy are highly predictive of successful ovulation induction and pregnancy outcome in cycles using luteal phase LA.

Timing of estrogen replacement therapy following hysterectomy with oophorectomy for endometriosis.

OBJECTIVE: To determine whether the immediate initiation of estrogen replacement therapy (ERT) in the postoperative period increases the incidence of symptom recurrence following total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) for the treatment of endometriosis. METHODS: In a retrospective cohort study, 95 women who underwent TAH with BSO for endometriosis at the Johns Hopkins Hospital during 1979-1991 and who subsequently received ERT were identified by computer search. Follow-up information was obtained from medical records, outpatient charts, and telephone surveys. Pain recurrence in patients who started ERT within 6 weeks after surgery and in those who delayed ERT for more than 6 weeks was compared and adjusted for length of patient follow-up and other covariates. RESULTS: Sixty women began ERT within the immediate postoperative period, and four (7%) of them had recurrent pain; 35 women began ERT more than 6 weeks after surgery, and seven (20%) of them had recurrent pain. The mean length of follow-up was 57 months. The difference in the crude rate of symptom recurrence following early and delayed initiation of ERT after TAH with BSO was not statistically significant (P = .09). Controlling for length of patient follow-up, no significant differences were observed between the two groups. Adjusting for covariates of stage, age, and postoperative adjunct medroxyprogesterone therapy, those who started ERT more than 6 weeks after surgery had a relative risk of 5.7 (95% confidence interval 1.3, 25.2) for pain recurrence. CONCLUSION: Although the number of patients in the study was too small to reach statistical significance in all analyses, these findings suggest that patients who begin ERT immediately after TAH with BSO are at no greater risk of recurrent pain than those who delay ERT for more than 6 weeks.

Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2 expression in GnRH agonist-treated uterine leiomyomas.

Gonadotropin-releasing hormone (GnRH) agonists are commonly used in the treatment of uterine leiomyomas, but little is known about their histological and cellular effects on these neoplasms. We examined a cellular proliferation index as determined by the nuclear antigen Ki-67 and proliferating cell nuclear antigen (PCNA) expression, estrogen receptor (ER), and progesterone receptor (PR) expression in 27 leiomyomas from patients treated with the GnRH agonist leuprolide acetate (LA) and compared them with 33 untreated controls. All leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6 months of LA treatment or in the follicular phase of the menstrual cycle in the untreated controls. Histological features examined included cellularity, nuclear atypia, vascular changes (dilated, thickened, or thrombosed vessels), edema, calcification, hemorrhage, necrosis, hyalinization, and mitotic activity. Although no difference was found between GnRH-treated and nontreated groups with respect to most histological features examined, immunohistochemical studies showed a significant decrease in the cellular proliferation index, ER, and PR expression in the LA-treated cases compared with nontreated controls. The cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and 36%, respectively, in the LA-treated group as compared with controls (P < .001). A subset of cases from the LA-treated and nontreated groups were also analyzed with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant difference between the LA-treated and nontreated groups was observed with both groups showing a strong (> 75% of cells) cytoplasmic staining pattern. Results of this study show that LA treatment of leiomyomas results in a decrease in number of cycling cells.

Dietary carrot results in diminished ovarian progesterone secretion, whereas a metabolite, retinoic acid, stimulates progesterone secretion in the in vitro perfused rabbit ovary.

OBJECTIVE: To determine the effects of dietary carrots and retinoic acid on P secretion in the in vitro perfused rabbit ovary. DESIGN: Controlled experiment. SETTING: Laboratory. SUBJECTS: Sexually mature New Zealand white rabbits. INTERVENTION(S): Experiments were done in vitro using an isolated rabbit ovarian perfusion system after acute feeding of carrots or with in vitro exposure to retinoic acid. MAIN OUTCOME MEASURE(S): Progesterone and E2 were measured in aliquots taken from arterial and venous cannulas. RESULT(S): Progesterone secretion during the in vitro perfusion of six ovaries is significantly diminished after the acute feeding of carrots. Human chorionic gonadotropin-induced P secretion also is significantly reduced. Progesterone secretion during in vitro perfusion on day 1 of pseudopregnancy was significantly increased in the perfusate samples from ovaries taken from rabbits not acutely fed carrots but that were exposed to retinoic acid. Progesterone secretion was increased but only marginally significant on day 11 of pseudopregnancy in perfusate samples from ovaries exposed to retinoic acid. CONCLUSION(S): Rabbit ovarian P secretion may be modified by carrots and carotene metabolites. This effect on steroid secretion may contribute to the relationship between hypercarotenemia and alterations in menstrual function.

Serum CA-125 screening for ovarian cancer in patients with dermatomyositis.

Ovarian cancer is the most overrepresented malignancy diagnosed in women with dermatomyositis. Unfortunately, screening with pelvic examination rarely detects this cancer prior to the development of metastatic disease. Our objective was to examine the use of serum CA-125 antigen levels in screening patients with dermatomyositis for ovarian cancer. A single blinded, case-control study was conducted in our institution of CA-125 levels in 14 women diagnosed with dermatomyositis between 1986 and 1993, 4 of whom subsequently developed ovarian cancer. In the 4 patients who developed ovarian cancer ("cases"), CA-125 determinations were performed on serum stored 5 to 19 months prior to the diagnosis of ovarian cancer. In the remaining 10 patients ("controls"), serum was drawn for CA-125 level determination at the time of the study, and simultaneous gynecologic and endovaginal ultrasound examinations were performed to exclude clinical evidence of ovarian cancer. All CA-125 serum measurements were performed simultaneously by a technician blinded to disease status using one diagnostic kit. CA-125 was found to be elevated in 2 patients with ovarian cancer (on serum obtained 5 and 13 months prior to the date of diagnosis of ovarian cancer) and in none of the control patients without clinical or ultrasound evidence of ovarian cancer (relative risk = 20, 95% confidence interval = [0.64, 666]). In these 14 patients, the sensitivity of CA-125 elevation for detection of ovarian cancer was 50%, and specificity was 100%. Serum CA-125 screening for ovarian cancer in patients having dermatomyositis may be useful; however, prospective studies are needed to confirm this and to determine the effect of screening on cancer stage at diagnosis and long-term survival.

Long-term estrogen therapy abolishes acute estrogen-induced coronary flow augmentation in postmenopausal women.

Postmenopausal estrogen replacement therapy (ERT) may reduce the clinical manifestations of coronary heart disease by favorably modulating coronary vasoreactivity. Intravenous ethinyl estradiol acutely increases coronary flow in postmenopausal women not receiving ERT. Because several vasoactive agents induce vasomotor tolerance when administered on a long-term basis, we hypothesized that long-term ERT attenuates the acute coronary vasomotor effects of intravenous ethinyl estradiol. To test this hypothesis, coronary hemodynamics were determined before and 15 minutes after intravenous ethinyl estradiol (35 micrograms) in 10 postmenopausal women who were receiving long-term conjugated ERT (group 1) and 10 who had never received ERT (group 2). Estradiol administration in group 1 was not associated with significant changes in coronary flow or resistance. However, women in group 2 exhibited a 28.6% +/- 6.5% (p < 0.001) increase in coronary flow and a 19.9% +/- 3.5% (p = 0.008) decrease in resistance. These results demonstrate that long-term ERT significantly attenuates the response of coronary arteries to the acute vasomotor effects of a high dose of estradiol. This response may be caused by long-term estrogen-induced coronary flow augmentation or to the development of vasomotor tolerance to estrogen.

Contraception in women with intercurrent disease.

Prescribing a contraceptive method for women with intercurrent disease poses a difficult clinical management problem for physicians. The contraceptive chosen may adversely affect the underlying disease of the patient. Conversely, failure of contraception could result in pregnancy, which could also adversely affect the patient's underlying disease. These factors must be taken into consideration in selecting appropriate and effective contraceptive agents to avoid complications and undesired pharmacologic interactions.

PIP: The selection of a contraceptive method for women with intercurrent disease necessitates complex balancing of the medical risks inherent in pregnancy and effects of the method on the underlying disease process. Presented in this review are contraceptive options for women with psychiatric, coagulation, cardiovascular, endocrine, and neurologic disorders as well as sickle cell disease and acquired immunodeficiency syndrome (AIDS). In women who are taking antidepressants or anti-anxiety medications, drug interactions can lower the efficacy of estrogen. Those with cardiovascular disorders face the potential adverse effects of exogenous steroids contained in oral contraceptives (OCs); at the same time, the need for effective methods is great given the increased cardiovascular demands of pregnancy. Current OC preparations can be safely prescribed to women with chronic nonvascular headaches, while the relationship between OC use and migraine remains inconclusive. In all cases, thorough counseling is essential to ensure informed consent and compliance.