Extended-cycle versus conventional treatment with a combined oral contraceptive containing ethinylestradiol (30 µg) and levonorgestrel (150 µg) in a randomized controlled trial.

The objective was to assess efficacy and safety of a combined oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in an extended-cycle vs. a conventional-cycle regimen. This first European randomized, active controlled, open, prospective, parallel-group trial was conducted in 48 German gynecological centers. 1,314 healthy, sexually active women aged 18-35 years were randomized. With an unadjusted PI of 0.483 (upper 95% CI: 1.237), the extended-cycle regimen fulfilled the contraceptive efficacy of EE/LNG, the requirements of the European Medicines Agency. The mean total number of bleeding days per year was significantly lower in the extended-cycle vs. the conventional-cycle regimen. Analyses of bleeding patterns showed a reduced total number of bleeding/spotting days per year in the extended-cycle vs. the conventional-cycle regimen. Cycle-associated complaints and AE were comparable in both groups. Both regimens were very well accepted. The extended-cycle regimen of EE/LNG was effective and well tolerated resulting in a lower number of bleeding days and a favorable bleeding pattern compared to the conventional-cycle regimen.

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Which contraception for women with epilepsy?

Clinical decision making which contraceptive regimen is optimal for an individual woman with epilepsy is one of the most challenging tasks when taking care of women with epilepsy. The bidirectional interactive potential of antiepileptic drugs (AEDs) and hormonal contraceptives needs to be taken into account. Enzyme inducing (EI)-AEDs may reduce the contraceptive efficacy of hormonal contraceptives. If combined oral contraceptives (COCs) are used in combination with EI-AEDs, it is recommended to choose a COC containing a high progestin dose, well above the dose needed to inhibit ovulation, and to take the COC pill continuously ("long cycle therapy"). But even with the continuous intake of a COC containing a higher progestin dose contraceptive safety cannot be guaranteed, thus additional contraceptive protection may be recommended. Progestin-only pills (POPs) are likely to be ineffective, if used in combination with EI-AEDs. Subdermal progestogen implants are not recommended in patients on EI-AEDs, because of published high failure rates. Depot medroxyprogesterone-acetate (MPA) injections appear to be effective, however they may not be first choice due to serious side effects (delayed return to fertility, impaired bone health). The use of intrauterine devices is an alternative method of contraception in the majority of women, with the advantage of no relevant drug-drug interactions. The levonorgestrel intrauterine system (IUS) appears to be effective, even in women taking EI-AEDs. Likelihood of serious side effects is low in the IUS users.

Role of testosterone in the treatment of hypoactive sexual desire disorder.

Hypoactive sexual desire disorder (HSDD) is a common clinical problem that may have a very negative impact on a woman's quality of life. Diagnosis and treatment is challenging, as one must keep in mind the complex web of factors influencing sexual functioning alone or in concert. Data suggest that androgens are significant independent factors affecting sexual desire, sexual activity and satisfaction, as well as other components of women's health such as mood and energy. For decades, physicians used various androgen preparations to improve sexual function in women, based on the results of smaller clinical trials and personal clinical observations when taking care of patients. Today, there is substantial body of evidence from randomized placebo-controlled trials that low-dose testosterone treatment is efficacious in women with HSDD who have an established cause of androgen deficiency such as surgical menopause. Recent data support the hypotheses that androgens may also be beneficial in naturally menopausal women or in premenopausal women with low circulating testosterone levels and a decrease in satisfying sexual activity. No single testosterone level has been found to be predictive for low female sexual function, even though women suffering from HSDD commonly have low testosterone levels. The most frequently reported side effects of testosterone treatment are mild hirsutism or acne. Long-term safety is not yet established. Several clinical trials are in progress to further investigate potential benefits and risks of androgen treatment in women with sexual dysfunction.

The historical response to female sexuality.

In the past, medical attitudes to female sexuality were grotesque, reflecting the anxiety and hypocrisy of the times. In the medieval world, the population feared hunger, the devil, and women, being particularly outraged and threatened by normal female sexuality. The 19th century attitude was no better as academics confirmed the lower intellectual status of women, particularly if they ventured into education. The medical contribution to this prejudice was shocking, with gynaecologists and psychiatrists leading the way designing operations for the cure of the apparently serious contemporary disorders of masturbation and nymphomania. The gynaecologist, Isaac Baker Brown (1811-1873), and the distinguished endocrinologist, Charles Brown-Séquard (1817-1894) advocated clitoridectomy to prevent the progression to masturbatory melancholia, paralysis, blindness and even death. Even after the public disgrace of Baker Brown in 1866-1867, the operation remained respectable and widely used in other parts of Europe. This medical contempt for normal female sexual development was reflected in public and literary attitudes. There is virtually no novel or opera in the last half of the 19th century where the heroine with "a past" survives to the end. The wheel has turned full circle and in the last 50 years new research into the sociology, psychology and physiology of sexuality has provided a greater understanding of decreased libido and inadequate sexual response in the form of hypoactive sexual desire disorder (HSDD). This is now regarded as a disorder worthy of treatment.

Hormonal changes in menopause and implications on sexual health.

INTRODUCTION: The menopause is characterized by an array of changes to the female body caused by modulations which occur in the production of estrogens and androgens. The ovaries are important sites of testosterone production in the peri- and postmenopausal women, but the contribution of testosterone pro-hormones from the adrenal glands falls precipitously to the extent where the ovaries cannot correct the deficit. This results in a net decline in circulating testosterone levels. AIMS: This paper gives an overview of this interesting subject area. Researchers have cogitated on the relationship between the physical effects of the menopause and the observed declines in testosterone levels, but it is now much clearer that falling testosterone levels cannot explain all of these changes. MAIN OUTCOME MEASURES: The cessation of follicular functioning results in a steep decline in the production of estrogens. This modulation is responsible for the physical manifestations of the menopause--hot flushes, sleep disturbances, mood changes, bleeding problems, local urogenital problems, vaginal changes, etc. METHODS: A review of the pertinent literature was conducted to investigate hormonal changes around the menopause. A précis of the salient information is presented here. RESULTS: Although the most obvious and well-known effects of the menopause are due to the decline of estrogen levels, the effects of falling testosterone levels are subtle, but by no means less significant. Reductions in sexual motivation, sexual arousal, vaginal lubrication, etc. are all associated with plummeting androgen levels. CONCLUSIONS: Today, several options exist for the treatment of the endocrinological changes associated with the menopause. Estrogen deficiency can be corrected with hormone replacement therapy and topical preparations for the genitalia. A new transdermal system for the administration of testosterone shows a great deal of potential for the treatment of androgen deficiency.

Lung cancer during pregnancy involving the products of conception and a review of the literature.

Approximately 1 per 1,000-1,500 pregnancies is complicated by maternal malignancies. Metastatic involvement of the products of conception is a rare event. There have been 62 cases of placental and/or fetal metastatic involvement originating from maternal cancer reported since 1866. Only 14 cases of lung cancer associated with pregnancy have been documented. We report on an additional case involving the products of conception, and the management of lung cancer in pregnancy is discussed based on an extensive review of the literature. The case of a 29-year-old woman presenting during the 31(st) week of gestation with metastatic non small-cell lung cancer to the placenta, liver and bone is described. The mother was delivered by caesarean section of a healthy baby girl during her 32(nd) week of gestation. The mother's postpartum course was complicated by disseminated pulmonary and bony metastases and malignant pericardial and pleural effusions causing the patient's death within 1 month after lung cancer was diagnosed. Malignancies spreading to the products of conception are melanoma (32%), leukemia and lymphomas (15%), breast cancer (13%), lung cancer (11%), sarcoma (8%), gastric cancer (3%) and gynecologic cancers (3%), reflecting malignancies with a high incidence in women of reproductive age. All lung cancers were diagnosed with widely disseminated, inoperable neoplastic disease, including distant metastases in 46%. The mean age was 35.1 years (range, 30-45 years) and 60% of patients had a history of tobacco use. The mean survival was 7.5 months (range: 1-42 months). Placenta involvement was present in 7 out of 15 cases. Fetal involvement was reported in only one case. Because there is no evidence of a direct adverse effect of pregnancy on the course of lung cancer, we recommend delivery at a time when enough fetal maturity can be assumed and the subsequent treatment of the mother.