Allan B. MacLean

Cognitive, sensory, and emotional changes associated with the menstrual cycle: a review

The hormones progesterone and estrogen and, more precisely, their sophisticated interdependent fluctuations over the course of the female human lifespan, have long been known to play a dominant role in the physiological development and homeostasis of the human female. What is only recently coming to light, however, is that the fluctuation of these two hormones also plays a crucial role in neurological and psychological development and function which impacts brain function, cognition, emotional status, sensory processing, appetite, and more. The ability of reproductive hormones to impact psychoneurological processes involves the interplay of several body systems, lending credibility to the view of premenstrual syndrome (PMS) as a disorder founded in real biochemical disturbances. The effects of the menstrual cycle on cognitive, emotional, and sensory function in the female of childbearing age are reviewed. In addition, recent evidence is discussed which confirms the biological basis of PMS as a real disorder of primarily autoimmune origin.

Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort

To assess long-term health effects of ovarian-stimulation drugs we followed-up for over 20 years a British cohort of 7355 women with ovulatory disorders, 43% of whom were prescribed ovarian-stimulation drugs, and identified a total of 274 deaths and 367 incident cancers. Relative to the general population, the cohort experienced lower mortality from most causes, including from all neoplasms combined, and lower incidence of cervical cancer, but higher incidence of cancers of the breast (relative risk: 1.13; 95% CI 0.97, 1.30) and corpus uteri (2.02; 1.37, 2.87). There were, however, no significant differences in the risk of cancers of the breast, corpus uteri, ovary, or of any other site, between women who had been prescribed ovarian-stimulation drugs and those who had not. Further analyses by type of drug and dose revealed a dose–response gradient in the risk of cancer of the corpus uteri (P for linear trend=0.03), with women given ⩾2250 mg of clomiphene having a 2.6-fold (2.62; 0.94, 6.82) increase in risk relative to those who were not treated. These findings do not support strong associations between ovulation-stimulation drugs and cancer risks, but they indicate the need for continued monitoring to establish whether risks are elevated in certain subgroups of users.

Physiological Changes Associated with the Menstrual Cycle: A Review

The cyclic hormonal changes that regulate the menstrual cycle are a significant biological influence on the female body, one with both physical and emotional ramifications. Menstruation is governed by tightly orchestrated changes in the levels of ovarian estrogen and progesterone, which produce varying responses in diverse tissues and organs. The skin, the largest organ in the body, is replete with estrogen receptors (in both dermis and epidermis) and to a lesser extent, progesterone receptors. Cyclically fluctuating levels of estrogen and progesterone influence numerous characteristics of the epidermis, including skin surface lipid secretion and sebum production, skin thickness, fat deposition, skin hydration, and barrier function. Dermal collagen content, which contributes to skin elasticity and resistance to wrinkling, is also influenced. Interestingly, estrogen levels also influence skin pigmentation and UV susceptibility, as well as resident microflora. In addition, changing hormone levels across the menstrual cycle produce measurable variations in immune function and disease susceptibility. An understanding of the profound influence that fluctuating estrogen and progesterone levels have on the biological responses of the premenopausal adult woman is critical to optimizing the efficacy of medical therapies in this population. Target Audience: Obstetricians & Gynecologists, Family Physicians Leaning Objectives: After completion of this article, the reader should be able to produce anticipatory guidance to patients regarding skin changes in pregnancy, predict clinical skin changes common in post menopausal women, and recall the physiology of the menstrual cycle.

Estrogen receptor expression in vulvar vestibulitis syndrome

OBJECTIVE A pilot study was performed to investigate the relationship between vulvar vestibulitis syndrome and estrogen receptor expression. STUDY DESIGN Women with a diagnosis of vulvar vestibulitis syndrome had tissue samples taken for vulvar estrogen receptor-alpha expression and this was compared with a control group. RESULTS The study group showed a significant decrease in estrogen receptor expression, and 50% of the samples did not exhibit any receptor expression. CONCLUSION There appears to be a subgroup of women with vulvar vestibulitis syndrome who exhibit abnormal estrogen receptor-alpha expression. This may be helpful in explaining why some women are resistant to medical treatment and may allow treatment to be prescribed more effectively.

The management of Paget's disease of the vulva*

Pagets disease of the vulva is an uncommon lesion, and gynaecologists and dermatologists generally have limited experience in its management. The British Society for the Study of Vulval Disease has established a register of cases, and we present a review of 76 cases registered to date. The majority of patients were treated by surgical excision and reconstruction, but non-surgical therapies are an option. Recent literature is reviewed to allow comparison.

Ovarian cancer and infertility: a genetic link?

A genetic mechanism may be responsible for the increased incidence of ovarian cancer in some infertile women (ie, those who failed to conceive despite treatment).

Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast.

The growth and metastasis of many cancers is due in part to loss of cell–cell adhesion. E-cadherin, plakoglobin and β-catenin are important in cell adhesion. Our aim was to examine the presence of these molecules in Pagets disease of the vulva and Pagets disease of the breast, and to correlate any differences in their expression with the presence of invasive disease or an underlying carcinoma. Sixty-three archival cases of Pagets disease of the vulva, including eight associated with invasive disease, and 23 archival cases of Pagets disease of breast, which included 10 cases with ductal carcinoma in situ alone, four cases with both ductal carcinoma in situ and invasive carcinoma, and five cases with underlying invasive carcinoma alone, were analysed immunohistochemically for expression of E-cadherin, plakoglobin and β-catenin proteins. The respective mRNAs were also detected by in situ hybridisation using digoxigenin-labelled cRNA probes. Seventy-six percent (41/54) of Pagets disease of vulva cases had >50% of Paget cells expressing the E-cadherin protein, compared with 28 % (2/7) of Pagets disease vulva with invasive disease. This result was significant, with a P-value of 0.039. Twenty-five percent (14/55) of the intraepidermal Pagets disease of the vulva cases had >50% of Paget cells expressing the plakoglobin protein, compared with 12% (1/8) of cases of Pagets disease of vulva with invasive disease, and for β-catenin, 9% (5/55) of the non-invasive Pagets disease of the vulva had >50% of Paget cells expressing β-catenin, compared with 12% (1/8) of Pagets disease of the vulva cases with invasive disease. Sixty-five percent (15/23) of the Pagets disease of the breast had >50% of Paget cells expressing E-cadherin, and for plakoglobin and β-catenin it was 17% (4/23) and 28% (6/21), respectively. The results were not significant. The results suggest that reduced expression of E-cadherin may have a role to play in the pathogenesis of invasive Pagets disease of the vulva. Abnormal plakoglobin expression may be involved in the formation of some cases of Pagets of the vulva and the breast.

Vulvar Cancer and the Need for Awareness of Precursor Lesions

Vulvar cancer continues to rise in incidence. In the absence of screening, attempts to reduce this cancer must focus on recognizing precursor lesions, namely, lichen sclerosus and vulvar intraepithelial neoplasia (VIN). The steep rise in human papillomavirus-repeated VIN will fall after the introduction of vaccination against human papillomavirus; in the meantime, those patients with VIN must be treated and then reviewed carefully and frequently. Lichen sclerosus has a 3% to 5% risk of progressing to vulvar cancer. Recommendations about which patients require referral to and follow-up by specialists/specialist clinics are given.

The detection of struma ovarii in two patients by radioimmunoscintigraphy

Struma ovarii is a rare benign tumor of the ovary. These cases detail the first identification of this pathologic condition, in vitro, by radioimmunodetection and coregistration.

Expression of cyclin D1 and retinoblastoma protein in Paget's disease of the vulva and breast: an immunohistochemical study of 108 cases.

Aims:  Loss of retinoblastoma protein expression and overexpression of cyclin D1 have been implicated in the development and progression of some cancers. Paget’s disease of the vulva (PDV) and Paget’s disease of the breast (PDB) are uncommon conditions and the pathogenesis of these diseases is still unclear. The aim was to examine the expression of the retinoblastoma and cyclin D1 proteins in PDV and PDB and to correlate any differences between PDV and PDB, and in the presence or absence of an underlying carcinoma.