Genetic aspects of premature ovarian failure

Wśród przyczyn zespołu przedwczesnego wygasania czynności jajników (POF) wymienia się dwie grupy czynników: zaburzenia prowadzące do zmniejszenia liczby pęcherzyków jajnikowych oraz stany prowadzące do przyśpieszonej atrezji pęcherzyków. W pierwszej grupie główną rolę odgrywają czynniki genetyczne, podczas gdy w drugiej takie przyczyny jak defekty enzymatyczne, zaburzenia autoimmunologiczne, czynniki jatrogenne, toksyny środowiskowe i zakażenia. W 1986 roku opisano rodzinne występowanie POF spowodowane delecją DNA w obrębie ramienia długiego chromosomu X (Xq). Kolejnymi chromosomami, które są istotne z punktu widzenia prawidłowej funkcji jajnika są: chromosom 21 (zawierający gen AIRE), chromosom 11 (gen podjednostki β FSH, gen ATM), chromosom 3 (gen odpowiedzialny za występowanie zespołu BEPS) oraz chromosom 2 (geny dla receptorów dla FSH i LH). W artykule omówiono rolę poszczególnych genów oraz wyniki odpowiednich badań epidemiologicznych.Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of β FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported

Aromatase inhibitors in the treatment of endometriosis

Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body’s oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis

Denosumab – a new medication in the treatment of postmenopausal osteoporosis

Osteoporosis is a chronic, systemic skeletal disorder characterised by decreased bone density. It leads to an increased risk of bone fractures – one of the major causes of disability in modern societies. Bisphosphonates are the most commonly used medications in the treatment of postmenopausal osteoporosis. Denosumab, a new approach to fracture prevention, is a fully human monoclonal antibody that targets nuclear factor-B ligand (RANKL), an important cytokine regulating formation and function of osteoclasts. Generally, denosumab is not used as initial therapy; however, in some cases it should be considered. It concerns patients at high risk of fracture, such as older patients who have difficulty with the dosing requirements of oral bisphosphonates or who have markedly impaired renal function. Denosumab can be also considered in patients who present intolerance or unresponsiveness to other therapies. Clinical studies have shown that denosumab is highly effective in increasing bone mineral density (BMD) in postmenopausal women regardless of the site analysed, as well as reducing the risk of bone fractures. The risk of developing antiresorptive, agent-induced osteonecrosis of the jaw related to denosumab therapy is low

Common Variants in One-Carbon Metabolism Genes (<i>MTHFR</i>, <i>MTR</i>, <i>MTHFD1</i>) and Depression in Gynecologic Cancers

We investigated the association between methylenetetrahydrofolate reductase (gene MTHFR 677C>T, rs1801133), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR 2756A>G, rs1805087), and methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (gene MTHFD1 1958G>A, rs2236225)—well-studied functional variants involved in one-carbon metabolism—and gynecologic cancer risk, and the interaction between these polymorphisms and depression. A total of 200 gynecologic cancer cases and 240 healthy controls were recruited to participate in this study. Three single-nucleotide variants (SNVs) (rs1801133, rs1805087, rs2236225) were genotyped using the PCR-restriction fragment length polymorphism method. Depression was assessed in all patients using the Hamilton Depression Scale. Depression was statistically significantly more frequent in women with gynecologic cancers (69.5% vs. 34.2% in controls, p MTHFD1 rs2236225 was associated with an increased risk of gynecologic cancers (in dominant OR = 1.53, p = 0.033, and in log-additive models OR = 1.37, p = 0.024). Moreover, an association was found between depression risk and MTHFR rs1801133 genotypes in the controls but not in women with gynecologic cancers (in codominant model CC vs. TT: OR = 3.39, 95%: 1.49–7.74, p = 0.011). Cancers of the female reproductive system are associated with the occurrence of depression, and ovarian cancer may be associated with the rs2236225 variant of the MTHFD1 gene. In addition, in healthy aging women in the Polish population, the rs1801133 variant of the MTHFR gene is associated with depression