Erica Terreno

Effects of an estrogen-free, desogestrel-containing oral contraceptive in women with migraine with aura: a prospective diary-based pilot study

BACKGROUND Migraine with aura (MA) is a contraindication to the use of combined oral contraceptives (COCs) because of the increased risk of ischemic stroke. Progestogen-only contraceptive pill (POP) is a safe alternative to COCs and it is preferable in women with cerebrovascular diseases or risk factors for stroke. STUDY DESIGN Prospective diary-based pilot study. Thirty women with MA (n = 15 who have never used COCs and n = 15 who had previously used COCs were diagnosed according to the International Headache Society criteria. The observational period lasted 9 months during which women filled in a diary with the clinical characteristics of headache attacks. After a 3-month run-in period, each subject received an estrogen-free desogestrel (DSG) (75 mcg/day)-containing OC (Cerazette(®); Schering-Plough, formerly NV Organon, Oss, The Netherlands). Follow-up evaluations were planned at the end of the third and sixth month of treatment. RESULTS The number (mean±S.D.) of migraine attacks was significantly reduced both in previous COCs users (from 3.9±1.0 to 2.9±0.8; p<.001) and nonusers (from 3.2±0.9 to 2.6±1.3; p<.02) following 6 months of POP use in comparison with the run-in period. Duration of headache pain did not differ significantly in both groups throughout the study. Interestingly enough, a beneficial POP effect on the duration (mean±S.D.) of visual aura (from 16.3±9.5 to 11.4±5.6 min) and on the total duration (mean±S.D.) of neurological symptoms (from 33.6±23.3 to 18.6±18.0 min) was only significantly reported by previous COCs users (p<.001, for both) by the end of the study period. The POP was well tolerated by each woman and the bleeding pattern was variable with a tendency towards infrequent bleeding. CONCLUSIONS The present study supports the use of the POP containing desogestrel in a population of women with MA and underlines a positive effect on symptoms of aura, especially in MA sensitive to previous use of COCs.

Effect of a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) in women with menstrually-related migraine (MRM)

BACKGROUND Combined hormonal contraception might worsen migraine in sensitive women, especially during the free-hormone interval, and raise concerns about the vascular risk. The characteristics of a contraceptive pill containing estradiol valerate/dienogest (E2V/DNG) might be of potential benefit in women with menstrually related migraine (MRM) who choose to use oral contraception for birth control. STUDY DESIGN This was a prospective diary-based pilot study. Thirty-two women (age >35 years) [n=18 who had never used combined oral contraceptives (COCs) and n=14 who had previously used COCs] diagnosed with MRMs according to the International Headache Society criteria were included. During the observational period, women filled in a diary with the clinical characteristics of migraine attacks. After a three-cycle run-in period, each subject received a COC containing E2V/DNG (Qlaira®/Natazia®; Bayer HealthCare, Berlin, Germany) administered using an estrogen step-down and progestogen step-up approach. Follow-up evaluations were scheduled at the last cycle of run-in and at the third and sixth cycles of treatment. RESULTS The number of migraine attacks was significantly reduced at the third (p<.001) and sixth cycles (p<.001) in comparison with the run-in period. A similar result was evident for the duration (p<.001 at the third and p<.001 at the sixth cycle) as well as for the severity of head pain (p<.001 at the third and p<.001 at the sixth month). Indeed, a significantly lower number of analgesics were used at the third cycle (p<.001) in comparison with baseline, and a further decrease was evident at the sixth cycle (p<.001) in comparison with the third cycle of E2V/DNG use. Interestingly, duration and severity of head pain were significantly correlated with the number of days of dysmenorrhea at the third cycle (r=.89, p=.000 and r=.67, p=.02; respectively) and at the sixth cycle (r=.76, p=.000 and r=.62, p=.04; respectively) in women without complete remission of menstrual cramps during the study period. CONCLUSIONS The present diary-based pilot study indicates that the use of a pill containing EV2/DNG for six cycles has a positive effect in women with MRM and suggests an association between dysmenorrhea with COCs use as a potential feature of refractory head pain.

Menopause and sexual desire: the role of testosterone

The present short review underlines the role of testosterone (T) in the motivational and satisfaction components of womens sexuality and critically discusses the strategies to treat hypoactive sexual desire disorder (HSDD), a condition of low desire associated with personal and/or interpersonal difficulties, which is more common in surgical menopausal women. There are multiple ways androgens target the brain regions (hypothalamic, limbic and cortical) involved in sexual function and behaviour. Even though circulating available androgens have been implicated in several domains of sexual response, they seem to be related weakly to symptoms, such as low sexual desire, poor sexual arousal, orgasm and diminished well-being in postmenopausal women. The possibilities of treating low sexual desire/HSDD are multifaceted and should include the combination of pharmacological treatments able to maximize biological signals driving the sexual response, and individualized psychosocial therapies in order to overcome personal and relational difficulties. Transdermal T has been shown to be effective at a dose of 300 µg/day both in surgically and naturally menopausal women replaced with estrogen or not, without any relevant side-effects. However, the decision to treat postmenopausal women with HSDD with T is mainly based on clinical judgement, after informed consent regarding the unknown long-term risks.

Sexual Function and Distress in Women Treated for Primary Headaches in a Tertiary University Center

INTRODUCTION Primary headaches are common in women and impact on their quality of life and psychosocial functioning. Few data are available on sexuality in female headache sufferers. AIM An observational pilot study was conducted to assess sexual function and distress in women treated for primary headaches in a tertiary university center. METHODS From a total of 194 women consecutively observed over a 3-month period, 100 patients were recruited. Migraine with and without aura, and tension-type headache, both episodic and chronic (CTTH), were diagnosed according to the International Classification of Headache Disorders. A detailed pharmacological history was collected, and anxiety and depression were assessed using validated scales. The Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised were administered. MAIN OUTCOME MEASURES The main outcome measures are sexual symptoms and distress in women treated for primary headaches. RESULTS More than 90% of the women had a median FSFI full-scale score under the validated cutoff, while 29% reported sexual distress. Hypoactive sexual desire disorder (HSDD) was diagnosed in 20% of the women and the pain domain score (median 2, score range 0-6) was highly affected by the head pain condition. However, the FSFI domain and full-scale scores did not significantly differ by headache diagnosis. The women with CTTH displayed a high rate of sexual distress (45.5%) and a strong negative correlation between desire, arousal, and full-scale FSFI score and number analgesics/month (r: -0.77, P=0.006; r: -0.76, P=0.006; and r: -0.68, P=0.02, respectively). Depression was positively correlated with sexual distress (r: 0.63, P=0.001) only in the women with CTTH. CONCLUSION Women treated for primary headaches were found to display a high rate of sexual symptoms and distress. Both migraine and tension-type headache were associated with sexual pain and HSDD, but women with CTTH seem to be more prone to develop sexual distress.

Management of hypoactive sexual desire disorder in women: Current and emerging therapies

Hypoactive sexual desire disorder (HSDD) is a common multifactorial condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. The general idea that HSDD is a sexual dysfunction difficult to treat is due to the large number of potential causes and contributing factors. Indeed, a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. There are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in Europe for postmenopausal women who experience HSDD as a result of a bilateral oophorectomy. Even though the role of sex hormones in modulating the sexual response during the entire reproductive life span of women is crucial, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as nonhormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. We conclude that the ideal clinical approach to HSDD remains to be established in term of efficacy and safety, and further research is needed to develop specific hormonal and nonhormonal pharmacotherapies for individualized care in women.

Headaches during pregnancy.

Among primary headaches, migraine is the form more sensitive to the ovarian hormonal milieu. Migraine without aura (MO) benefits from the hyperestrogenic state of pregnancy and the lack of hormonal fluctuations, while migraine with aura (MA) presents distinctive features. Indeed, a very strong improvement of MO has been documented across gestation, and only a minority of pregnant women still suffers during the third trimester. On the other hand, fewer women with MA report improvement or remission, and new onset of aura may be observed during pregnancy. After delivery, breastfeeding exerts a protective action on migraine recurrence. The persistence of migraine during gestation seems to affect neonatal outcomes, and several studies indicate a link between migraine and an increased risk of developing gestational hypertension/preeclampsia and other vascular complications.

Transdermal hormonal therapy in perimenstrual migraine: why, when and how?

Experimental and clinical evidence is strongly in favor of a role for estrogens in migraine. It is clear that estrogen fluctuations represent trigger factors for the attacks, while the resolution of these fluctuations (menopause) may be associated to the remission or, conversely, to the worsening of the disease. However, the exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. The exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. In this review, we summarize clinical and preclinical data that are relevant for the role of estrogens in migraine and we discuss how estrogen modulation can be exploited positively to improve hormonal-related migraine.

Hypoactive sexual desire disorder: can we treat it with drugs?

Hypoactive sexual desire disorder (HSDD) is a common multidimensional condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. There are a number of potential causes and contributing factors to HSDD and a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. It is clearly evident that sex hormones play a crucial role in modulating sexual response during the entire reproductive life span of women. On the other hand, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as non-hormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. However, there are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in Europe for post-menopausal women who experience HSDD as a result of a bilateral oophorectomy. That being so, the ideal clinical approach remains to be established in term of efficacy and safety and further research is needed to develop specific pharmacotherapies for individualized care of women with sexual dysfunction of any age.