The article discusses the causes, symptoms, and management of premature and early menopause, emphasising the impact on women's health and the importance of hormone therapy and lifestyle adjustments.

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Aetiology

1. Premature menopause (PM) could be either spontaneous or predominantly induced. Induced PM has been universally due to gonadotoxic chemotherapy cycles, and surgical removal of gonads.
2. Spontaneous menopause is not uncommon; it is approximately seen in 0.3-1.1% of reproductive-age women and this poses a serious threat to fertility and a significant challenge to infertility specialists.
3. It is noteworthy here that although Premature ovarian insufficiency (POI) has been used interchangeably with PM it is hypothesised to keep in the perspective of the “permanent” nature of the insult due to underlying risk factors.
4. Age at menarche, breastfeeding of the previous child, and age at first pregnancy, play a very important role in determining the onset of menopause. In the PAN India study by Ahuja et al in 2016, there is a strong association between the early onset of menopause and various factors such as illiteracy, poor socio-economic background, underweight, parity, and age at pregnancy. [3]
5. Other reported factors include nulliparity, usage of oral contraceptive pills, cigarette smoking, alcohol intake, dietary patterns and socio-economic status, parity status, and Body mass index of the woman. [4,5]
6. Heavy smokers have destructive consequences on the normal functioning of the human tissues and ovaries are no exception. The consumption of these products has an anti-estrogenic impact on the human body leading to functional estrogenic resistance. [5–7]

Major causes related to the onset of premature menopause:

1. Genetic disorders- Ovarian dysgenesis is seen in 30% of the cases. Chromosomal abnormalities are more commonly associated with POI when presented early. Other causes include familial, Trisomy 18, 13; [6,8]

2. Metabolic- 17α Hydroxylase deficiency, Galactosemia [9]

3. Immunological- reported in 30-60% of the cases. Autoimmune causes of premature menopause are thyroid diseases, mumps, systemic lupus erythematosus, hyperparathyroidism and Addison's disease. They are more common in late-onset presentations. [10]

• Smoking
• Autoimmune disease [6]
• Infection
• Iatrogenic
• Surgery
• Drugs

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Symptoms

Usually, a year of amenorrhea can be used to define menopause but even shorter durations of amenorrhea are equally meaningful in the context of POI. In most cases, they present as secondary amenorrhea after the complete establishment of the cycles.

It is often picked up as long-standing amenorrhea in postpartum and post-abortal women and could be infrequently associated with women taking combined oral contraceptives.

Menstrual irregularities may result from a variety of etiologies, mainly due to fluctuating estrogen levels. The symptoms include:

• Hot flashes
• Night sweats
• Emotional labilities
• Vvaginal dryness
• Sleep disturbances

Early menopause is linked to a number of symptoms, including:

• Vasomotor symptoms (Hot flushes and night sweats)
• Vaginal symptoms (vaginal dryness and dyspareunia)
• Urinary symptoms (frequency, urgency, incontinence and atrophic cystitis)
• Sexual dysfunction
• Sleep disturbances

Other symptoms are:

• Headache
• Depression
• Anxiety
• Irritability
• Skin atrophy
• Joint pains
• Cancer phobia
• Pseudocyesis
• Lack of concentration

The beginning of hot flushes can be unpredictable and manifest as frequent bouts of severe heat or flushing that start on the face or upper neck and move to the upper chest abruptly, explosively, and painfully.

Anxiety, blotches of red skin, and palpitations are all possible side effects of hot flashes. Hot flushes last for 2-5 minutes, varying in frequency with some women experiencing episodes multiple times in a day but decreasing over time. [10,11]

Premature menopause can cause urethral caruncle, and dysuria, with or without infection, urge and stress incontinence.

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Signs

1. There are characteristics of loss of vaginal rugae, shortening and narrowing of the vagina. There is an overall loss of mucosal elasticity with reduced vaginal secretions and loss of vaginal transudate.
2. The reduced vaginal secretions and the delayed timing of vaginal lubrication during sexual intercourse significantly contribute to dyspareunia in women with premature menopause. [10]
3. Urogenital diaphragm weakening and urogenital atrophy are brought on by lower oestrogen levels. The atrophic alterations in the female lower genital tract result in symptoms related to stress incontinence, dysuria, and urethral discomfort.

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Investigations

Documented elevation in circulating gonadotropins along with low estradiol levels detectable on 2 occasions, at least 4 to 6 weeks apart, is required before labelling a reproductive-age woman with the diagnosis of POI in relation to irregular or nonexistent menstruation.

To diagnose ovarian failure, gonadotrophin values in the premature menopausal range are required; however, due to the disease's sporadic appearance, repeat assays may be needed every two to four weeks.

Women with Follicle follicle-stimulating hormone (FSH) levels above 40 mIU/ml may not have viable ovarian follicles on biopsy and such women may be regarded as having undergone permanent ovarian failure. [12,13]

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Management

1. The recommendations by Faubian et al may be considered for the management of PM [14]
2. Hormone therapy is beneficial for women who experience menopause before the age of 45 due to primary ovarian insufficiency or bilateral salpingo-oophorectomy. It also helps prevent the negative effects of premature estrogen deficiency on the cardiovascular system, bone health, and neurocognition.
3. Many medical associations advise women who are going through an early or premature menopause to think about hormone therapy at least until they reach the normal age of menopause.
4. To get blood estradiol concentrations close to those of menstruation women, higher dosages of estrogen (at least 100 µg of transdermal estradiol) could be required.
5. Women with primary ovarian insufficiency have a 5–10% chance of spontaneous conception and require appropriate counselling about contraception if pregnancy is not desired.
6. Despite the fact that testosterone has been demonstrated to enhance female sexual function, it is not currently routinely advised for women who have undergone bilateral salpingo-oophorectomy or primary ovarian insufficiency.
7. Counselling regarding bone health includes recommendations for weight-bearing exercise, muscle strengthening, fall risk assessment, smoking cessation and avoidance of excess alcohol intake, along with a daily dietary intake of calcium - 1200 mg of &  vitamin D - 600–1000 IU, including supplements if needed.
8. Psychological assistance may be beneficial for women who have undergone bilateral salpingo-oophorectomy or primary ovarian insufficiency. This support can help address concerns related to early menopause, such as sexual dysfunction, changes in self-image, and loss of fertility.

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Long-term health consequences

Cognitive disturbances: Apart from its vital function in a woman's ability to conceive, estrogen has numerous other significant impacts on the body, including lowering LDL cholesterol, increasing HDL cholesterol, inducing vasodilation, and preventing osteoporosis.

Women who experience an early drop in estrogen are more susceptible to depression, osteoporosis, cardiovascular illness, parkinsonism, and dementia or cognitive impairment.

Regions that are necessary for learning and memory, including the prefrontal cortex, hippocampus, amygdala, and posterior cingulate cortex, contain substantial estrogen receptors. [15]

To properly respond on appropriate timescales and regulate brain energy metabolism, estrogen is necessary. One example of this is the ovarian-neural estrogen axis. Changes in either the availability of estrogen or its receptor network (e.g., β-receptors) can affect intracellular signalling, neural circuit function, and energy availability in brain neurons. [16]

There is a connection between cortisol, stress, and cognition; however, this hypothesis has not been extensively tested in cases of premature menopause. [17]

Mental health: Psychological functioning is relatively poor in women with early menopause compared to women with menopause at the average age. [18]

Women who experience early menopause may find it helpful to be referred to a psychologist or sex therapist because they frequently struggle to adjust to their new self-image, sexual dysfunction, and the decreased fertility brought on by estrogen shortage.

Fertility preservation may be considered in women before initiation of chemotherapy or radiation treatment and in women with POI, and counselling with a fertility specialist is recommended. [19]

Bone health: The calcium and vitamin D intake guidelines for women going through early menopause are the same as those for women going through menopause at their normal age.

For women between the ages of 51 and 70, the Institute of Medicine suggests a daily consumption of 1,200 mg of calcium and 600 IU of vitamin D. Giving up smoking and abstaining from excessive alcohol consumption, evaluating one's risk of falling, engaging in regular weight-bearing exercise and strengthening muscles, and consuming 1,200 mg of calcium and 800–1000 IU of vitamin D per day, with supplements if necessary, are all recommended. [20]

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Anusha Devalla is an MS, DNB Gynaecology working as Assistant Professor in the Department of Obstetrics and Gynaecology at AIIMS Hyderabad