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Nursing Practice Keywords Menopause/Andropause/ /Sex /HRT Systems of life This article has been Reproductive system double-blind peer reviewed In this article... ● Age-related changes to the reproductive tracts ● Effects of reduced sex secretion in men and women ● Symptoms of the perimenopause, menopause and andropause

Anatomy and physiology of 8: the reproductive system

Key points Authors John Knight is senior lecturer in biomedical science; Yamni Nigam is In middle and old associate professor in biomedical science; both at the College of Health and age, there is a Science, Swansea University. gradual loss of fertility and changes Abstract In men and in women, brings about changes to the reproductive in the production of system that eventually lead to infertility – although men stay fertile for longer. These sex hormones changes are partly due to dramatic fluctuations in the production of sex hormones such as oestrogen, and . In the perimenopause and In the peri- menopause, most women experience physical and psychological symptoms that can menopause and be extremely disruptive. Although less dramatic, the changes prompted in men by menopause, women the andropause can lead to erectile dysfunction and a loss of . Article 8 in our experience series on the effects of ageing explores the changes occurring in the female and male considerable reproductive systems, and the role of hormone replacement therapy. fluctuations in the levels of oestrogen Citation Knight J, Nigam Y (2017) Anatomy and physiology of ageing 8: the and progesterone reproductive system. Nursing Times [online]; 113: 9, 44-47.

Perimenopause and menopause often hroughout the fertile years, the diminish and oestrogen production cause burdensome male and female reproductive declines, which in most women triggers symptoms such as organs (testes and ) pro- the menopause around the age of 51. The hot flushes, vaginal Tduce ( and ova) speed of ovarian ageing is determined pri- dryness and mood which, through , may marily by genetics, although oxidative changes fuse to form an . The production of stress, apoptosis and environmental fac- gametes is orchestrated by a cascade of tors also play a role. Premature ovarian Men also undergo hormones and growth factors, many of failure (POF) can be triggered by surgery, hormonal changes, which have complex effects on the body. In radio- or , autoimmune but the symptoms of middle and , the reproductive sys- reactions, and infections caused, for the andropause are tems undergo significant changes: a example, by the virus and cyto- less dramatic than gradual decline in fertility and fluctua- megalovirus (Amanvermez and Tosun, those experienced tions in the production of sex hormones, 2016; Broekmans et al, 2009). by women the latter triggering anatomical and physi- ological changes in distant organs and tis- The perimenopause Hormone sues. This article examines these changes In women, the first episode of menstrual replacement therapy and explores some of the treatments avail- () marks the onset of can relieve able to alleviate their consequences. . The prime -bearing years symptoms in both correspond to the period between men and women, Female reproductive system menarche and perimenopause (Dutton but has risks and Ovaries and Rymer, 2015). Before the menopause, side-effects As women age, there is a progressive when ceases and women decline in the number of ovarian follicles, become infertile, the hormones that drive which gains speed in the fourth decade of the start to fluctuate. This life; the number and quality of ova perimenopausal phase, which can last 2-10

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years, is often accompanied by increasing irregularity of the menstrual cycle. Fig 1. Ageing of the female reproductive tract Although perimenopausal women are still : Loss of muscle and eventual Ovaries: Reduction in number of ovarian fertile, becomes more difficult. cessation of menstrual cycle follicles maturing leads to gradual decline The symptoms of the perimenopause in fertility. Levels of oestrogen begin to are similar to those of the menopause. drop, triggering the menopause – Some women experience few symptoms, typically around age of 51 but for others the perimenopause can be Fundus Fallopian tubes: extremely challenging, since fluctuating Shrinkage in length, loss hormone levels can cause physical and of ciliated epithelia and psychological symptoms such as hot loss of mucosa Uterus Body contribute to loss of flushes, , mood swings and fertility feelings of sadness (Wagner, 2016). The menopause : Loss of elasticity, shortening in The irregular menstrual cycles character- Opening of the cervix: length, reduction in vaginal secretions and Reduced cervical thinning of epithelial lining all increase risk istic of the perimenopause eventually secretions of tears, bleeding and infection cease completely. Strictly speaking, the menopause is the cessation of periods for 12 months (Goodman et al, 2011). In most of Hot flushes Menopausal are also at risk of the world it occurs in the early 50s, with Around three in four women experience : the bladder and ure- some variation. Around 95% of women go hot flushes in the perimenopause and thra are sensitive to oestrogen (both have through the menopause between 44 and 56 menopause (Bit.ly/NHSCHoicesHotFlushes). oestrogen receptors), so it seems likely years, the average age being 50.7 (Freeman, They are described as a rapid heat increase, that decreased oestrogen levels contribute 2015). Many factors that precipitate POF particularly in the face, neck and chest, to urethral shrinkage and urinary inconti- can also trigger early menopause (Dutton often with sweating and . The nence (Santoro et al, 2015). tissue is and Rymer, 2015). Since no more ova are length of time women experience them also oestrogen sensitive and women often being released, it is impossible for post- varies between 4 and 10 years; most experi- notice a loss of supporting connective menopausal women to become pregnant ence them every day and a third have more tissue in the (Chahal and Drake, without fertility treatment. than 10 a day (Committee on Practice Bul- 2007); age-related skin thinning and loss of letins – Gynecology, 2014). skin elasticity can exacerbate this. Hormonal changes Hot flushes appear to be related to Follicle-stimulating hormone (FSH), increased levels of FSH and decreased Mood changes and secreted by the , drives the levels of oestrogen. Decreased oestrogen Fluctuating concentrations of FSH, oes- menstrual cycle. It stimulates the develop- seems to affect serotonin levels in the trogen and progesterone are often associ- ment of ovarian follicles, and as these hypothalamus, causing fluctuations in the ated with mood changes. Despite incon- enlarge they secrete the female sex hor- set point of the thermoregulatory centre; sistencies in the literature, it is generally mone oestrogen. In perimenopausal and this leads to vasodilation and increased accepted that normal fluctuations in hor- menopausal women, FSH levels remain blood flow in the skin (Santoro et al, 2015). mone levels – whether in the premenstrual high – or are higher than in premenopausal stage of the menstrual cycle, during preg- women – but FSH is unable to stimulate Vaginal and dryness nancy or in the perimenopausal years – can follicular development. Eventually, follic- The menopause is associated with a loss of be associated with negative psychological ular activity ceases altogether, leading to a elasticity and shrinkage in the length of symptoms. The perimenopause is also rapid decline in oestrogen secretion. the vagina. The epithelial lining becomes associated with poor memory and concen- Similarly, luteinising hormone, which thinner and infiltrated by neutrophils, tration, problems with other people and triggers , is secreted at normal or while the production of natural lubri- low self-esteem. Other psychological higher than normal levels (Burger et al, cating secretions slows down, increasing symptoms are , and 2007), but without mature follicles, no ova the risk of tears, bleeding and infection. In rapid mood swings, but not necessarily low can be released so menopausal women this changing environment, faecally mood (Freeman, 2015; Cohen et al, 2005). become infertile. derived species of bacteria may become A previous history of depression or pre- dominant over the lactobacilli populations menstrual syndrome is associated with an Symptoms and clinical features typically seen in premenopausal women. increased risk of clinical depression in the As during puberty and pregnancy, the Lactobacilli produce lactic acid, so their perimenopause and menopause. Women transition to and through menopause is depletion reduces the acidity of the vagina, may also have pre-existing pathologies – associated with dramatic fluctuations in resulting in a neutral or alkali pH that can such as metabolic syndrome, the sex hormones oestrogen and proges- encourage the growth of Candida albicans or – that are associ- terone. Symptoms are diverse and some- and other micro-organisms (Milsom, ated with depression and depressive symp- times unique to the individual, but there 2006). These vaginal changes can make toms. It is unclear if there is an increased are four that most women experience to sexual intercourse uncomfortable or painful risk of clinical depression in the perimeno- varying degrees: hot flushes, vaginal dry- (), and can reduce libido; pause (Freeman, 2015), so clinical depression ness, mood changes and sleep distur- 27-60% of menopausal women are affected should not be regarded as a normal feature

CATHERINE HOLLICK CATHERINE bances (Santoro et al, 2015). by vaginal dryness and dyspareunia. of either perimenopause or menopause.

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Sleep disturbances Sleep problems become more common Fig 2. Ageing of the male reproductive tract with age. In women, the risk of is Bladder 41% greater than in men. Around 25% of women aged 50-64 report sleep problems – Prostate: Decreased secretions from rising to 50% in postmenopausal women the seminal vesicles and prostate gland (Santoro et al, 2015; Ameratunga et al, lead to reduced volume of ejaculate. Benign prostatic hypertrophy may 2012). Many reasons for sleep disturbances compress urethra, making urination during the menopause have been sug- difficult gested: hot flushes and night sweats, anx- iety, depressive symptoms and sexual dys- Penis: Reduced testosterone levels can cause shrinking and erectile dysfunction function (Jehan et al, 2015). Not all studies agree that the menopause is directly linked Testes: Reduced testicular mass leads to sleep problems. A recent study showed to reduction in sperm production and no statistically significant differences in testosterone secretion. Sperm ducts sleep quality between premenopausal and gradually become less elastic menopausal women (Tao et al, 2016).

Decreased health The cervix (neck of the womb) consists The andropause Reduced oestrogen levels can lead to a of a smooth muscle layer overlaid by a Although most men do not experience the decrease in bone density and increased risk mucus-producing cervical epithelium. profound physiological and psychological of fractures. Menopausal women lose up to Cervical mucus is essential to female fer- changes that many women go through, 15% of their bone mass (Riggs and Melton, tility, aiding sperm to pass through the they do undergo hormonal changes indic- 1986). Significant losses in the spongy bone cervical aperture and enhancing sperm ative of the so-called andropause – often of the vertebrae contribute to the curva- motility and maturation. The menopause inaccurately referred to as the male meno- ture of the spine often seen in postmeno- is associated with a reduction in cervical pause (Chahal and Drake, 2007). In their pausal women with osteoporosis. secretions which contributes to reducing 30s, men start to experience a decline in fertility (Gorodeski, 2000). serum testosterone levels of around 1-1.4% Fallopian tubes per year. This is thought to be due to a Shrinkage in the length of the Fallopian reduction in the number of interstitial tubes, loss of ciliated epithelia and loss of Testes and sperm ducts cells that synthesise testosterone and a mucosa have been reported (Hwang and Most men show an age-related reduction reduced availability of free testosterone in Song, 2004). Since the Fallopian tubes are in testicular mass (Chahal and Drake, 2007) the blood (Matsumoto, 2002). the site of and are responsible with an associated reduction in testos- for transporting the fertilised ovum to the terone and sperm production. Since sper- Physiological and psychological uterus, these changes contribute to the age- matozoa are produced in huge numbers, symptoms related reduction in fertility, and may most men remain fertile until their 80s and Compared with the literature on the peri- explain why older women are at increased 90s, although erectile dysfunction (ED) menopause and menopause, there is little risk of ectopic pregnancy (Bouyer et al, 2003). may be a problem. The sperm ducts, which research on the andropause. Reduced tes- carry sperm from the testes during ejacula- tosterone levels are associated with various Uterus and cervix tion, gradually become less elastic because physiological and psychological changes: The is the inner mucosal of an accumulation of collagen (sclerosis). l Increased body (usually visceral); layer of the uterus that is shed during men- l Reduced muscle and bone mass; struation and then rebuilt under the influ- Prostate gland and seminal vesicles l ED and reduced libido; ence of oestrogens. When oestrogen pro- The secretions from the seminal vesicles l Increased risk of anaemia; duction decreases, this rebuilding is and prostate gland, which form the semen l Memory problems; gradually compromised, until it becomes in which sperm swim, decrease with age, l Sadness; impossible and menstruation ceases. so the volume of ejaculate is reduced. Due l Irritability; The myometrium, the middle layer of to the parallel decrease in sperm numbers, l Loss of facial and pubic hair; the uterus, is composed almost entirely of sperm concentration remains fairly con- l Lethargy; smooth muscle fibres. In childbirth its stant, which helps maintain male fertility. l Decreased endurance (Jakiel et al, 2015). contractions push the baby through the Secretions from the prostate contain anti- birth canal. In the menopause, it begins to bacterial factors, so their decrease may Penis and erectile dysfunction shrink. Oestrogen helps to maintain the increase the risk of . Reduced testosterone levels can cause the myometrium, so its reduction is thought A common age-related problem is penis to shrink, both in its flaccid and erect to contribute to the loss of smooth muscle benign prostatic hypertrophy (BPH), a states. However, in most men, the earliest fibres – although the mechanisms of myo- gradual, non-malignant increase in the symptom of the andropause is a loss of metrial atrophy remain unclear (Mwampa- size of the prostate contributing to age- libido, often accompanied with problems gatwa et al, 2013). related micturition difficulties. BPH may achieving an and maintaining it The perimetrium – the thin outer cause symptoms that are similar to those to the point of . The number of serous layer of the uterus – appears to of prostate cancer, so investigations may decreases and weaker erections

CATHERINE HOLLICK CATHERINE change little with age. be needed to rule out malignancy. become more common. Men who smoke

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or have pre-existing pathologies such as Modifiable risk factors the Menopause: 21st Century Solutions. , blood pressure problems or ath- The ageing of the reproductive tracts, and Cambridge: Cambridge University Press. Freeman EW (2015) Depression in the menopause erosclerotic occlusion are at higher risk of the changes and symptoms brought about transition: risks in the changing hormone milieu as ED. Today, ED can be treated by techniques by the menopause and andropause, are observed in the general population. Women’s Midlife Health; 1: 2, 1-11. such as counselling and such inevitable. However, certain lifestyle Goodman NF et al (2011) American Association of as sildenafil (Viagra) (Bansal, 2013). changes may delay, or reduce the effects of Clinical Endocrinologists Medical Guidelines for the menopause or andropause – although Clinical Practice for the diagnosis and treatment of menopause. Endocrine Practice; 17(Suppl6): 1-25. 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Annals of Anatomy; 186: 3, 263-269. l Treating osteoporosis and reducing the lowers sperm count and quality (Sengupta Hyland A et al (2016) Associations between risk of bone fractures; and Nwagha, 2014). lifetime tobacco exposure with infertility and age l  at natural menopause: the Women’s Health Improving muscle strength; A low body mass index (BMI) and being Initiative Observational Study. Tobacco Control; 25: l Reducing vaginal dryness; undernourished are both associated with 6, 706-714. l Reducing hot flushes and night sweats; an earlier menopausal onset. The effect of Jakiel G et al (2015) Andropause – state of the art 2015 and review of selected aspects. Menopause l  Improving sleep; an increased BMI is less clear: some studies Review; 14: 1, 1-6. l Reducing ; show that it is linked with a later meno- Jehan S et al (2015) Sleep disorders in l Improving memory; pausal onset (Akahoshi et al, 2002), others postmenopausal women. 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American Journal of Medicine. 118(Suppl Part 7: the endocrine system Aug 12B), 93-97. Committee on Practice Bulletins – Gynecology For more on this topic go online... Part 8: the reproductive system Sep (2014) Management of menopausal symptoms. Part 9: the immune system Oct Obstetrics and Gynecology; 123: 1, 202-216. l The menopause: effects on the pelvic Part 10: the musculoskeletal system Nov Dutton PJ, Rymer JM (2015) Physiology of the floor, symptoms and treatment options Part 11: the skin Dec menstrual cycle and changes in the Bit.ly/NTMenopause perimenopause. In: Panay N et al (eds) Managing

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