Barri PN, Coroleu B, Chueca A, Devesa M

MEDICAL MANAGEMENT AND FERTILITY PRESERVATION IN PATIENTS WITH ENDOMETRIAL CANCER

It is well known that 5% of endometrial cancers (EC) occur in patients <45 years, some of whom may not have accomplished their potential fertility. Likewise, nulliparity of any origin as well as anovulation and/or polycystic ovarian disease are common risk factors for EC.
Given that patients with endometrial cancer often present at an early stage with well differentiated tumours, conservative management is possible. Medical treatment can be performed with different doses of progestins, GnRH analogues, insulin sensitizing agents, ovulation induction protocols and in vitro fertilization techniques (IVF). Although there are many published studies that refer to pregnancies obtained in these patients, some points need further study.
- Pretreatment evaluation
- Optimal local or systemic treatment
- Safety of ovarian stimulation protocols in these patients
- Need for hysterectomy alter child-bearing
We should identify three different clinical situations
a) Infertility treatment and later endometrial carcinoma
b) Fertility preservation in patients with endometrial cancer
c) Coexistence of pregnancy and endometrial carcinoma
There are data reporting that in 0.1% of endometrial biopsies carried out in infertile patients an endometrial cancer was discovered. This is an important issue because endometrial biopsy is no longer included in the infertility diagnostic work-up and sonographic evaluation of the endometrium may not be enough in high-risk patients (chronic anovulation, PCO etc.)
In our experience, we have not observed any significant increase in the standardized incidence rate (SIR) for endometrial carcinoma in our infertile population treated with ART.
There are numerous studies proving that systemic or local treatment with progestins might be useful for the conservative treatment of early-stage endometrial cancers. Insulin sensitizing agents have also been used successfully for this purpose. After medical treatment most patients underwent IVF in order to achieve a pregnancy although in some cases embryos were replaced in surrogate carriers.
We are aware of 12 cases of concomitant endometrial cancer and pregnancy. These cases were diagnosed during the pathological evaluation of chorionic villi obtained in the curettage carried out when these patients miscarried. Although a look at the existing evidence gives grounds for optimism, there are still some unresolved issues such as:

- Possible treatment of grade 2 tumours
- Pretreatment evaluation MRI, hysteroscopy, 3-D ultrasound, biochemical markers.
- Optimal regime of progestins, dose, duration, route of treatment
- Safety of ART in these patients
- Need for hysterectomy alter childbearing
- Oophorectomy at the time of hysterectomy.

 

back to top...

Baulieu EE

RU486 (MIFEPRISTONE) NEW ANTIPROGESTINS AND NOVEL USES

The most studied activities of antiprogestins relate to the field of fertility regulation. The properties of newer derivatives will be presented. Some recently obtained information on the mechanisms of activation and inactivation of the progesterone receptor will be summarized. Physiological, medical and ethical aspects will be analized, with emphasis on safety. The use of antiprogesterone in contraception, at the time of delivery, and in mid-aged women will be discussed. Unexpected activity of RU486 in the Central Nervous System will be briefly described.

back to top...

Bazot M, Daraï E

WHICH IMAGING FOR DEEP INFILTRATING ENDOMETRIOSIS.

Surgical management of endometriosis has been assuming a prominent role in treatment of deep infiltrating endometriosis (DIE). However, a precise preoperative mapping of different locations of DIE is mandatory for optimal surgical planning. DIE is characterized by the presence of fibrosis and muscular hyperplasia in the different locations of DIE giving highly suggestive non-invasive imaging features including thickening, nodules or masses associated or not with cystic areas.
The aims of this presentation are:
• to describe the different non-invasive imaging techniques, including ultrasonography, MR imaging and CT scanner useful for a preoperative diagnosis of DIE
• to recall the different criteria for the diagnosis of deep infiltrating endometriosis (DIE)
• to assess the relevance and accuracy of these non-invasive imaging techniques for diagnosing specific locations of DIE in comparison to surgery and histology
• to propose a flowchart of the different imaging techniques for optimal pre treatment planning.

back to top...

Benagiano G

EVOLUTION OF HUMAN SEXUALITY

Human sexuality has always been loaded with multiple meanings, although until recently, reproduction has been considered the main focus of human sexual activity. This strategy remained basically unchanged from the beginning of the genus Homo to the beginning of the 20th century, although human sexuality began to lose its exclusive reproductive meaning very early in the evolution of the genus. Furthermore, with a female accessible to the male throughout the menstrual cycle, humans began to feel a need for avoiding, rather than seeking conception during intercourse. For this reason, effective contraception had a tremendous impact on the lives of women: mastering reproduction became a means to achieve equality between the two sexes. During the XXth century, after sex without reproduction became a reality, also reproduction without sex became possible; this was followed by reproduction in menopause and one day, reproduction without gametes may also become a reality. These true revolutions drew the attention of religious moralists and, in this respect, Catholic ethicists have been at the forefront of the battle against what they consider a de-humanising of the reproductive process; an attitude in sharp contrast with that taken by Judaism and – at least in part – by Islam. The strict position of Catholic theology follows the concept developed by early Christian Church fathers that intercourse is totally justifiable, even within marriage, only in order to procreate. This concept became the official doctrine of the Catholic Church until the 20th century. Today, some cautious overtures have been made and the Church has formally recognised that sexuality and intercourse can, in specific cases, be expressions of conjugal love independent from procreation..

back to top...

Bitzer J

FEMALE SEXUALITY AND CHRONIC PELVIC PAIN

Introduction: Chronic pelvic pain (CPP) is a diagnostic and therapeutic challenge for gynecologists. As a symptom it may be caused by a specific well defined disease like endometriosis or it may become a disease by itself without being explainable by any tissue damage or organic cause. Female sexual dysfunction is also a complex clinical condition in which frequently biological, psychological and social factors interact. The management of women with CPP and FSD requires a comprehensive diagnostic and therapeutic concept. Methods: Research of the literature and analysis of own cases. Results: Empirical studies of women with chronic pelvic pain have indicated a correlation with FSD in many but not in all patients. The challenge for the physician lies in exploring the biomedical and psychosocial factors that contribute to the pain and at the same time look into the impact of these factors on the female sexual response. In clinical practice we found 3 types of patients: Women with FSD as a direct cause of CPP; Women with FSD conditioned by comorbities of CPP; Women with FSD contributing to CPP; Therapeutically it is important to help women regain their sexual function and health in spite of CPP by adapting the therapeutic approach to the individual clinical case Conclusion:Sexual health in patients with CPP may be compromised and should be considered as a health problem in its own right. It should be the target of diagnostic and therapeutic interventions to improve the quality of life of these patients.

back to top...

Genazzani AR

CARDIOVASCULAR PROTECTION IN WOMEN

Sex steroid hormone direct the function of reproductive and non-reproductive tissues, and between these is the vascular wall. At this level, estrogen triggers rapid vasodilatation, exerts anti-inflammatory effects, stimulates endothelial growth and migration and protects the vessels from atherosclerotic degeneration. Based on this intriguing evidence, it seems clear that the evolutionary process must have selected sex steroids as powerful and finely tuned regulators of functions that are related to survival and evolutionary success. The cardiovascular system is a prominent target of sex steroids, and the lack of these hormones throughout life, i.e. during periods of amenorrhea or after the menopause, has a profound impact on the function of the CVS. Menopause may represent a time in woman’s life when the administration of sex steroids might turn into a significant protection of the vessels in the long run, eventually decreasing the risk of cardiovascular diseases. However, it seems that this may be limited to a specific “window” of exposure, that is early after the menopause, and possibly only to specific hormonal preparations and ways of administration.

back to top...

Graziottin A

THE MASTCELL: THE DIRECTOR OF CHRONIC PELVIC PAIN ORCHESTRA

Background: Mast cells (MCs) play a key role in acute and chronic inflammation. They are distributed in all organs and vascularized tissue, where they work as immune sentinels. They are recruited to the sites of inflammation, where they orchestrate the inflammatory response. MCs contain different angioactive, pro-inflammatory and neurotrophic factors, packed in vesicles which differentially release their content outside the cell into the tissue, according to the type and timing of damaging factors (“agonists” of the degranulation process).

Aim of the presentation: to update the knowledge and understanding of mastcell’s role in chronic pelvic pain (CPP), focusing on endometriosis, vulvar vestibulitis, irritable bowel syndrome and interstitial cystitis.

Method: review of the literature

Results: Increasing evidence supports the prominent role of up-regulated mastcells in the maintenance of chronic inflammation and in the shifting from nociceptive to neuropathic pain in the affected tissues, contributing to CPP.

Conclusions: MCs are the real conductor of the inflammatory process. In CPP, MCs are the maintaining contributor of chronic inflammation, leading to the shift between nociceptive and neuropathic pain. New therapeutic lines should consider reduction of agonists and/or using drugs (“antagonists”) that can down-regulated the release of proinflammatory, angiogenic and neurotrophic factors from the mastcells..

back to top...

Lachowsky M

ELDERLY COUPLES, QUALITY OF LIFE AND SEXUALITY, A PSYCHOSOMATIC APPROACH

From what age on is one elderly, would not OLD be appropriate or is it simply a more delicate way for our society to avoid those unpalatable words, old, age and ageing? As healthcare specialists we know that post-menopausal women may experience pain/dyspareunia mostly due to hormonal depletion, that older men may suffer from erection difficulties, and that those conditions can have dramatic consequences on a couple's quality of life. Older couples do need our assistance, not only our prescriptions but also our counselling, which might make all the difference. Psychosomatic approach does not mean defining THE psychology of the elderly couple, as we do not believe there is such a profile. It means taking all parameters of their life in account, with practical interrogations about their years together, how and what they shared, their intimacy, their sexuality before..and now, not neglecting life-events and souvenirs. Empathy, time, the right distance, the right words, discreet but tactful questions, even silences, are the necessary tools, combined to scientific knowledge. If the doctor is not afraid to broach those topics, he will enable his patients to be open about themselves, their couple, their privacy, their sexuality.

back to top...

Morice P, Uzan C, Gouy S

FERTILITY PRESERVATION IN CERVICAL CANCER

The gold standard for the surgical management of stage IB1 cervical cancer (< 4 cm) is based on radical hysterectomy with pelvic lymphadenectomy. In young patients with early stage disease, 2 classes of conservative management could be discussed to preserve the subsequent fertility: - In patients with tumor size < 2 cm, “usual” histologic subtype (adenocarcinoma, squamous cell or adenosquamous lesion), negative node and length of free margin > 5 mm, radical trachelectomy could be proposed. Some teams considered that presence of lymphovascular space involvement is a contra-indication to propose such management. More than 800 cases of radical trachelectomy are now reported in the literature. Oncological results seems to be very close (or similar) to radical surgery. - The other conservative management proposed in patients with “higher” risk factor (tumor size between 2 et 4 cm) is the use of chemotherapy followed by simple conisation. Such management could be proposed only in patients with “usual” histologic subtype and absence of nodal involvement. Nevertheless furthers studies are needed to evaluate the oncological results of such management because very few cases are actually reported.

back to top...

Petraglia F, Ciani V, Lazzeri L, Calonaci F, Di Marco C, Centini G, Florio P, Luisi S

ENDOCRINE CONTROL OF ENDOMETRIOSIS

Endometriosis is a multifactorial disease characterized by the presence of endometrial-like tissue outside of the uterus, estrogens (E) have a role in the pathogenesis of endometriosis since endometriosis is an estrogen-dependent disease in women in reproductive age. Endometriotic implants contain ERs, and express aromatase cytochrome P450. ER genes polymorphisms may be responsible for estrogen action as modulators of the estrogenic response, with a potential impact on endometriosis. Polymorphisms in the ERa Pvull gene is associated with the recurrence of endometriosis, probably through an increase of the ERa receptor activity. Progesterone resistance in endometriotic tissue from laboratory and clinical observations may be accounted by the presence of the inhibitory PR-A and the absence of the stimulatory isoform PR-B. The presence of the PR gene polymorphic allele is associated with a reduced risk of deep infiltrating endometriosis. Endometriotic cells express mRNA of various peptides whose expression is increased in comparison to the eutopic endometrium. Endometrial epithelial and stromal cells express CRH and urocortin mRNA, with a significant increased peptide expression and secretion during the secretive phase of the menstrual cycle. Urocortin is also expressed from endometriotic cells significantly more than in healthy endometrium.

back to top...

Belaisch-Allart J

THE ELDERLY PREGNANT WOMAN

Many women are now delaying childbearing in most economically developed countries. The objective of this study is to evaluate the pregnancy complications and adverse outcome with increasing maternal age. Increasing maternal age is associated with elevated risks for pregnancy complications (diabetes, hypertension) and adverse outcome (prematurity, hypotrophy and stillbirth). These risks should be considered when counselling older women and in their subsequent antenatal management.

back to top...

Birkhäuser MH

HRT FOR MENOPAUSAL SYMPTOMS AND QUALITY OF LIFE

Quality of life depends on personal, cultural, social and medical factors. In postmenopausal women, Health Related Quality of Life (HRQOL) is an essential determinant of quality of life (QoL). HRQOL represents those parts of quality of life that directly relate to an individual’s health and diseases. It includes the domains of physical, psychological, social and spiritual functioning, as well as general well being. The decrease of HRQOL in chronically ill women may be superimposed to the decrease of QoL induced by menopause itself. Although treatment of climateric symptoms may improve QoL independently from an improvement of the underlying chronic disease, it is still widely believed that menopause should not be medicalized and that menopauseassociated adverse consequences on QoL have to be accepted because the risks of Hormone Replacement Therapy (HRT) do not justify its use. However, it cannot bde contested that climacteric symptoms are a direct consequence of a decrease in estrogen levels. Therefore, replacement therapy with estrogen is logical and, because of its efficacy, the therapy of choice. HRT remains the most efficacious treatment of hot flushes. Estrogens improve also mood, sexuality, well-being and QoL. If HRT is indicated, the benefits outweigh the risks. However, despite solid clinical outcome data on efficacy and safety when HRT is begun for symptoms in the early post menopause, many physicians and lay people still believe that hormone use is risky and undesired. This opinion is based on data obtained in the WHI in elderly women in their later post menopause, but outdated by the conclusions drawn from the latest data data from both the WHI and the Nurses’ Health Study. For any decision about the management of menopause and for the evaluation of the risks and benefits of HRT, QoL has to be taken into account. Studies done in sympto-matic women in their peri- and early post-menopause show clearly that QoL including sexuality are significantly decreased by oestrogen deficiency and improved by HRT. In most women the benefits of HRT are maintained at low/ultra-low doses whilst side-effects and risks are minimized. In conclusion, HRT should not be withheld to women suffering from climacteric symptoms and a low QoL due to menopause, except if there is an unequivocal contraindication.

back to top...