INTRODUCTION:

Adolescence is the time of life between puberty and psychophysical maturity when crucial endocrinological, metabolic, somatic and psychological changes occur in girls. During this process, sequential phases mark the maturation of the complex endocrinological system that comprises the hypothalamus, pituitary gland, ovary, and their interactions ^1-3. Healthy reproductive function is the expected at the end point of this process. The timing of this process is individual-specific, within a broad range of normality. The most frequent menstrual disorders are polymenorrhea, oligomenorrhea and dysmenorrhea^4-7.

Menstrual abnormalities are more common among younger girls, becoming less frequent as they grow older, 3–5 years after menarche^8-11. Clinical evidence from the literature indicates that in third year after menarche the interval between bleeding periods is in the range of 21–34 days, with a flow lasting from 3 to 7 days and a mean menstrual blood loss of 35 ml (range 5–80 ml) ^4-6.

Menopause is a normal part of aging. It refers to the time when ovaries reproductive function ends and these stop producing eggs and the hormones namely estrogen and progesterone¹². Menopause occurs when a woman has not had her period for 12 months or longer¹³. Most women reach menopause between the ages of 45 and 55, with the average age being around 51 years. However, about 1% of women experience menopause before the age of 40 years. This is known as premature menopause. Menopause between 41 and 45 years of age is called early menopause¹⁴. It is marked by amenorrhea, increased gonadotrophin levels and oestrogen deficiency¹⁵.

Premature or early menopause is the result of an accelerated aging process determined by genetic or non-genetic causes and involving all tissues and organs throughout the body, including the ovaries¹⁶. Premature menopause or early menopause can be spontaneous or induced by medical interventions such as chemotherapy or radiation treatment and surgical interventions like bilateral oophorectomy i.e surgical removal of the ovaries. Bilateral oophorectomy in premenopausal women, estradiol levels drop, testosterone levels drop by 40–50%, and follicle-stimulating hormone levels rise abruptly. Women undergoing bilateral oophorectomy continue to have lower levels of androgens than naturally menopausal women even beyond 65 years of age¹⁷. When menopause is surgically induced, it is associated with a rapid decline in ovarian hormone levels and consequently more severe menopausal symptoms. These symptoms include hot flashes, sleep disturbances, mood liability, and decreased energy¹⁴.

With Premature ovarian insufficiency, follicle-stimulating hormone levels are elevated and estradiol levels are low, but sporadic increase in estradiol may occur¹⁸. Ovarian androgens remain age-appropriate in these women¹⁹. Ovarian failure caused by cancer therapy, when permanent, is associated with elevated follicle-stimulating hormone levels and reduced estradiol levels similar to natural menopause; androgen function has not been well-characterized. Overall, different consequences from the different types of menopause may relate to the extent of disruption of the hypothalamic-pituitary-ovarian axis as much as to the reduced levels of circulating sex steroid hormones²⁰.

The most commonly reported symptoms among women in high-income countries are vasomotor symptoms including hot flushes, vaginal dryness, insomnia, fatigue, and joint pain^{19, 21-22}. Premature menopause and early menopause, whether spontaneous or induced, are associated with long-term health risks which may include premature death, cardiovascular disease, neurologic disease, osteoporosis, psychosexual dysfunction, and mood disorders. Estrogen mitigates some but not all of these consequences. The most common interpretation of these findings is that premature or early menopause is the first step in a chain of causality leading to tissue or organ dysfunctions and lesions via hormonal mechanisms²⁰. Symptoms attributed to menopause vary between individuals and cultures, which has been attributed to general aging, menopausal fluctuations, or socially constructed phenomena²³. Some of the adverse outcomes may be prevented or minimized by estrogen therapy started after the onset of premature and early menopause. However, estrogen alone does not prevent all long-term consequences and other hormonal mechanisms are probably involved¹⁴.

Most common reason for lack of awareness in female of reproductive age group is their inability to relate their symptoms to menopause and their belief that the symptoms experienced by them are owing to some other ailment in their body. Their unawareness may lead to complications after menopause. The premenopausal stage is one of the key stage of menopause and therefore, awareness among women in this stage is very important.

MATERIALS AND METHODS:

Study Design:

An observational cohort study on evaluation of early menopause symptoms in post-hysterectomy and premature ovarian insufficiency in women of reproductive age group was conducted by department of Pharmacy Practice in collaboration with Department of Gynaecology, M.M. Institute of Medical Science Hospital, Mullana-Ambala (India) with a sample size of 100 patients on the basis of inclusion and exclusion criteria. The study was conducted for a period of 6 month from November 2018 to April 2019. The study protocol and all the other documents which were related to the study were approved by Institutional Ethics Committee (.IEC/MMDU/1321.). Patients were selected after analyzing their present illness, menstrual and menopausal history. The purpose and objectives of the study were explicitly explained to the patient and their guardian. Informed consent was signed by the patients or their guardian, willing to participate in the study. The data of the patient was recorded on the basis of Questionnaire (Menopause Rating Scale) and was analysed.

Study Units (Inclusion Criteria/Exclusion Criteria):

All indoor and outdoor adult patients aged between 18 – 45 years with history of post-hysterectomy (abdominal, vaginal, laparoscopic), premature ovarian insufficiency, hormonal replacement therapy and any other endocrine dysfunction were included in the study. Patients of postmenopausal (>46 years) age, having any malignancy and history of chronic disease of heart, liver, lungs and kidney disease, HIV/TB were excluded from the study as these have been identified as potential confounding factors.

Method of Data Collection:

The selected patient group as per the above inclusion/exclusion criteria were included in the study. A case report form was designed for collection of general information about the patient’s age at menopause, address, contact number, weight and height, dietary habits, level of education, any associated disease, risk of fractures, oral contraceptive user/non-user. Also detailed information about patient menstrual cycle included age at menarche, approximate date of last menstrual period, pattern of menstrual cycle (regular/irregular), length of each cycle, duration of bleeding (in days). The data for severity of symptoms /complaints in women related to menopause collected by Menopause Rating Scale (MRS). The MRS basically associated with psychological, somatic and urogenital symptoms. Thus, three independent domains namely Psychological domain including depressive mood, irritability, anxiety, physical and mental exhaustion, Somato-vegetative domain including hot flushes, heart palpitations, sleep problems, joint and muscular pains and Urogenital domain comprising of sexual problems, dryness of vagina and bladder problems have been identified. Each of these symptoms/items measured on the scale of 0-4 points wherein 0 indicated no complaints while 4 inferred severe symptoms depending on the severity of the complaints perceived by the women. Counselling was provided to patient about menopausal symptoms and awareness was imparted about hormonal replacement therapy (HRT).

RESULT:

The patient sample size (n=100) was selected as per inclusion and exclusion criteria. Out of these 100 respondents, majority of patients were in between the age of 36-40 years (49%), followed by number of patient between the ages of 41-45 year (24%). Least number of patients were falling under the age group of 31-35 year (23%), followed by age of 25- 30 year (only 4%) (table-1).

Table 1: Distribution of Premature Menopausal Patients as per Menopausal age

S. No.	Age of menopause	Number of patients	Percentage of Patients
1	25-30	04	04
2	31-35	23	23
3	36-40	49	49
4	41-45	24	24

Data from Body Mass Index (BMI) interpret that majority of patients having BMI range between 18-25 (32%) were found to be normal, followed by number of patients having BMI range between 25-30 (47%) were found to be overweight. Least number of patients was in BMI range between 30-35 (17%) were found to be obese class I, followed by number of patients having BMI range between 35-40 (4%) were found to be obese class II (table-2).

Table 2: Distribution of Premature Menopausal Patients on the Basis of BMI

S. No	Categories	BMI Range	Number of patient	Percentage of patient
1	Normal	18 -25	32	32
2	Overweight	25-30	47	47
3	Obese class I	30-35	17	17
4	Obese class II	35-40	4	04

In the study, premature menopausal patients were found with some other concomitant illness included Hypothyroidism (36%), Type 2 Diabetes Mellitus (24%), Hyperthyroidism (14%) and Hypertension (2%) and others (24%), as shown in figure 1.

Figure 1: Distribution of Premature Menopausal Patient on the Basis of Concomitant illness

The Pie chart (figure 2) represents the causes of premature menopause which reveals that the main causes of premature menopause were spontaneous (41%), followed by surgery (29%), surgery with contraceptive (14%) and contraceptive (5%).

Figure 2: Distribution of Premature Menopausal Patients on the Basis of Causes of Menopause

On the basis of MRS Questionnaire, the psychological symptoms was analysed and compared between premature menopause group and control group. The data reveal that the maximum number of premature menopause patients was found to be in moderate group (37%) followed by severe group (27%), mild group (20%) and least number of patient in none group (16%), as compared with control group in which the highest percentage of women in none group (60%), followed by mild group (30%) and moderate group (10%). The comparison of MRS domains (psychological, somatic and urogenital) were done between Premature Menopause group and Control group (table-3).

Table 3: Comparison of MRS domains between Premature Menopause group and Control group

S. N	Symptoms	Psychological Domains			Somatic Domains			Urogenital Symptoms
S. N	Symptoms	MRS for Psychological Symptoms	Percentage of Premature Menopause Group	Percentage of Control Group	MRS for Somatic Symptoms	Percentage of Premature Menopause Group	Percentage of Control Group	MRS for Urogenital Symptoms	Percentage of Premature Menopause Group	Percentage of Control Group
1	None	0-1	16	60	0-2	02	30	0	01	20
2	Mild	2-3	20	30	3-4	07	20	1	03	40
3	Moderate	4-6	37	10	5-8	36	50	2-3	32	40
4	Severe	>7	27	0	>8	55	0	>4	64	0

The comparison between premature menopause group and control group on the basis of somatic symptoms as assessed by MRS. It showed that the maximum number of premature menopause patients showed severe somatic symptoms (55%) followed by moderate group (36%) and mild group (7%). Very few patients didn’t reveal any somatic symptoms and thus constituted none group (2%). In sheer contrast, the percentage of women from control group followed the trend: moderate group > none > mild group > severe case.

The urogenital symptoms of premature menopause group compared with control Group revealed that the maximum number of premature menopause patients was found to be in severe group (64%) followed by moderate group (32%), mild group (3%) and least number of patient in none group (1%). While in control group, the equal and highest percentage (40%) of women constituted both moderate group and mild group which was followed by none group (20%) while none of the women from control group showed severe somatic symptoms.

DISCUSSION:

Menopausal age is a vital and most relevant biomarker for loss in fertility and also as an indicator to reveal increased risk multiple mid-life diseases and problems. Many of these diseases can be prevented by timely intervention of lifestyle modification, menopausal hormone therapy, or other supplementations such as calcium, Vitamin D, and micronutrients. In India, menopausal age is less than our counterparts in the Western world. This means that the fertility potential of Indian women starts compromising early, thus necessitating us to start with the preventive measures much early. Premature or early menopause is the result of an accelerated ageing process determined by the genetic and non-genetic causes and involving all tissues and organs throughout the body²⁴. The present observational study was carried out in women of rural area around Mullana (Ambala District) to evaluate age of premenopause and postmenopausal symptoms with the help of pretested questionnaire.

Average age of menopause of an Indian woman is 46.2 years much less than their Western counter parts in which 51 years is age of menopause²⁵. Natural menopausal age of North Indian women as cited in literature is 45.5 ± 4.9 years, however, present study revealed that majority of women living in this area had menopausal between age 36 to 45, with a mean of 42±3.7 years. The premature menopausal age in Indian women is 44.69 ± 3.79 years and in northern it was 45 ± 3.6, however in our study both premature menopause and its average age showed marked deviation, the former value being 36 to 40 years with the latter being 38±2.3 year.

Literature findings indicate that there is a relationship between lifestyle (including nutrition and body mass index) and the severity of menopausal symptoms. Some studies reported that obesity and decreased physical activity can lead to early menopause²⁶. Obesity and overweight also reduce the quality of life at menopause, which is due to the increased prevalence of chronic diseases, negative self-imagine, and decreased physical activity in obese women²⁷. The results of present study indicate that the premature menopause was most common in rural area, illiterate, as well as women had body mass index between 25 to 30 (overweight).

Although women experience similar symptoms in menopause due to hormonal changes primarily to estrogen deficiency, but additional factors include vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, psychiatric symptoms, cognitive decline, and sexual problems²⁸. The study explores the prevalence of metabolic syndrome in premature menopausal women as concomitant illness i.e. thyroid dysfunctions and type 2 DM, was significantly higher.

Premature menopause means a woman’s ovaries have spontaneously stopped working without unknown factor as idiopathic premature menopause but some possible causes include autoimmune disease, genetic conditions, viral infections, radiation therapy or chemotherapy. The reason for premature menopause in our study may be spontaneous (41%), surgery (29%) and use of contraceptives (27%).

Perimenopausal patients present with vasomotor, psychological, and urological symptoms as well as disturbances in bleeding pattern²⁹. In a documented study, Psychiatric morbidity (31% had depressive disorder, 7% had anxiety) was significantly more in perimenopause women having lesser education, from rural background, with a history of psychiatric illness in the family, a later age of menarche, and in the late stage of perimenopause³⁰. The data from present study also showed similar and significant rate of psychologic distress in premature menopausal women as compare to normal menopausal women.

Multiple population and community-based studies confirm that about 27% to 60% of women report moderate to severe symptoms of vaginal dryness or dyspareunia in association with premenopause³¹. Results of present study revealed that premature menopausal women experienced higher prevalence of somatic and urogenital symptoms as compared to normal menopausal women.

For women who experience premature or early menopause, HRT is strongly recommended until the average age of menopause (around 51 years), In our study, it was also found that a very few women (3%) of premature menopause received hormonal replacement therapy (HRT) to treat menopausal symptoms.. As a part of our study and service/duty as a pharmacist, we counselled and made aware the women with premature menopause regarding benefits of hormonal replacement therapy to overcome the symptoms related to premature/early menopause.

CONCLUSION:

While the symptoms of menopause can significantly impact a woman’s quality of life, not all women experience the same symptoms. Most symptoms begin in perimenopause, or the transition into menopause, and can last 7-10 years in some women. The menopause transition is a good time to reassess woman’s health. Deep understanding of the fact that menopause may impact chronic disease risk will help women in making smarter choices and lead a healthier life. In conclusion, premature menopausal women should be considered in a special category so that health care providers can plan strategies for them accordingly.

ACKNOWLEDGEMENTS:

We are highly thankful to the Head of Department (Gynecology & Obstetrics), MMIMSR for their support in this research work and also to the Ethical committee of M.M Institute of Medical Science & Research, for the permission given.

CONFLICTS OF INTEREST:

The authors declare no conflict of interest.

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Received on 04.06.2020 Modified on 20.04.2021

Research J. Pharm. and Tech. 2022; 15(5):2035-2040.

DOI: 10.52711/0974-360X.2022.00336