Changes in the Female Reproductive Organs at the Menopause.
Fig. [84].—Sagittal section through the ovary of a girl aged 16.
In considering the changes that take place in the female reproductive organs at this period of life, we must distinguish between the proper period of the climacteric, with its various manifestations antecedent to and associated with the irregularity and ultimate cessation of menstruation, from the condition of old age in which menstruation has actually and completely ceased, in which the menopause has been fully accomplished, and in which the changes of senescence have set in at once in the organs of the reproductive system and in the organism as a whole.
The most important and most significant changes of this sexual epoch are unquestionably the anatomical alterations in the ovaries. A good many years ago I undertook an investigation whose purpose was to follow the natural involution of the graafian follicles from the time of the climax on into old age, and for this purpose I examined a very large number of ovaries of women at ages varying from 42 to 75 years (Archiv. für Gynecologie, Bd, XII., Heft 3).
Throughout these years a slow but continuously progressive atrophy proceeds in the ovaries; they become smaller and denser, diminishing especially in height and width; their surface becomes extremely uneven; and in extreme old age they wither away until no more is left in the region formerly occupied by the ovaries than a flattened fibro-vascular thickening (Figs. 84–88). The histological characteristic of the changes in the ovary which proceed gradually from the commencement of the menopause to extreme old age, may be summed up as consisting in a continual increase and new formation of the connective tissue stroma at the expense of the cellular layer, accompanied by retrogressive metamorphosis of the graafian follicles.
Fig. [85].—Sagittal section through the ovary of a woman aged 72 years.
The connective tissue ground substance of the ovary increases from the periphery towards the centre, and progressively compresses the epithelial structures of the organ. In the outermost layer of the ovarian stroma, the so-called tunica albuginea, the strata of short, dense connective tissue fibres increase notably in number, so that whereas at first three layers at most could be distinguished, the tunic ultimately comes to consist of from six to eight layers; at the same time also the interior ovarian stroma becomes exceedingly dense, so that numerous well-defined interlacing bundles of fibres can be made out in its substance.
The first retrogressive metamorphosis which can be observed in the graafian follicles is fatty degeneration, the formation of granule spheres. Whilst the membrana propria (the theca folliculi) of the follicle remains quite unaltered, we observe in the membrana granulosa, in addition to the ovum, and the ordinary cells of this layer, spherical aggregates of fat droplets, the granule spheres, which continually increase in size, until ultimately of the cellular contents of the follicle nothing whatever remains, and it now appears full of granule spheres and fluid. The theca folliculi has now lost its spherical shape, and assumes an ovid form (Fig. [89]).
In a later stage of the degeneration of the graafian follicle, it appears as a vesicular body with a relaxed wall, thrown into numerous folds, this folded wall being formed by the theca folliculi. The cavity of the follicle is reduced to a mere cleft, filled with a transparent substance, and the space between this cleft and the inner surface of the theca folliculi is occupied by round cells and a fibrous intercellular substance, and is traversed by a vascular network. This second stage of the retrogression of the follicle may therefore be designated the stage of vesicular degeneration (Fig. [90]).
Fig. [86].—Diagrammatic representation of the Graafian Follicle.
Fig. [87].—Ovary of a girl aged 19 years. (Normal size.)
Fig. [88].—Ovary of a woman 72 years of age. (Normal size.)
In the last stage of this retrogressive metamorphosis, we find the follicle completely transformed to a fibrous mass. It appears as an elongated oval body, much lobulated, connected with the surrounding stroma by thick strands of fibres; a trace of the original cavity can still be distinguished in the form of a narrow cleft, without distinguishable contents. The tissue of this body consists of connective tissue fibres, with interspersed nuclei and nuclear fibres (Fig. [91]).
The three stages I have observed in the retrogression of the follicle, of which I have given a summary account above, may, I think, be explained in the following manner: When the woman’s reproductive activity ceases, the graafian follicles become subject to a retrogressive metamorphosis, a fatty degeneration setting in in the cells of the membrana granulosa and in the ovum, until ultimately the whole of the granular epithelium has undergone atrophy. The follicle now undergoes a vesicular transformation with shrinkage of its cavity, and with the formation of a new tissue which appears to be young connective tissue. As time goes on, this new connective tissue is formed in increasing quantities, until finally the entire follicle is transformed into a firm fibrous mass.
Fig. [89].
Thus we are led to infer that the gradual but extensive thickening of the tunica albuginea (i. e., the outer, condensed layer of the ovarian stroma), which, as we have seen, always occurs at the climacteric period, offers a hindrance to the bursting of the follicles as they mature, and in this we find the explanation of the irregularity of menstruation and of the various troubles which attend the performance of that function at the time of the menopause. It is reasonable to assume that the resistance of this thickened tunica albuginea is responsible for the fact that the interval between the bursting of the successive follicles is now greater than normal, as much as six or eight weeks—this retardation of menstruation being one of the commonest ways in which the onset of the menopause is first manifested. Another phenomenon connected with the onset of the menopause also finds a plausible explanation in the anatomical grounds just mentioned. As already pointed out, in parous women the menopause sets in later than in nulliparae. At every pregnancy, the ovaries share in the more abundant nutrition of all the reproductive organs, due to the general dilatation of the intrapelvic vessels which accompanies this process; hence the ovaries become larger, richer in lymph, and therefore softer, the cellular elements increase in size, and perhaps also in number, and it is readily conceivable that in such ovaries the cellular elements are able for a longer time to resist the induration and the new formation of connective tissue which occur at the climacteric.
The numerous nervous disturbances of the climacteric epoch would appear also to depend upon the hyperplasia of the ovarian stroma which we have observed to be the characteristic anatomical change in the ovaries at this period of life.
Fig. [90].
Associated with the fibrous transformation of the graafian follicles there is, however, a failure of the so-called internal secretion of the ovaries, a matter to which much attention has recently been paid. Brown-Séquard has especially maintained that the ovaries secrete a substance which enters the blood, a substance which, notwithstanding the fact that its presence cannot be proved either by chemical or any other means known to us, yet is of considerable importance for the maintenance of the equilibrium of mental and physical well-being. It is supposed that the various profound disturbances of the general system occurring at the menopause[[52]] are dependent upon the cessation of this internal secretion of the ovary—disturbances which rise to a maximum as the atrophy of the ovary proceeds, and which only gradually pass away after a considerable lapse of time.
After the menopause is completely over, in the ovaries, as in other parts of the female reproductive organs, the signs of senile degeneration make their appearance.
In old women, we find the ovaries either shrunken to the form of small fibrous cords, or else degenerated to form cysts of smaller or larger size, the stroma surrounding these cysts being extremely hard, dense, and tough.
Fig. [91].
Fig. [92].—Sagittal section through the Cervix of a woman 26 years of age. Dendriform branched Glands.
Fig. [93].—Sagittal section through the Cervix of a woman 65 years of age. Glands which have undergone Cystic Degeneration.
Fig. [94].—Cervix of a woman 70 years of age. The Cervical glands have undergone Cystic Degeneration.
Whereas at the commencement of the climacteric period, the uterus commonly exhibits a slight increase in size, owing to the condition of passive hyperaemia already described, subsequently a gradual diminution in the size of the organ may be observed. This atrophy begins with the portio vaginalis and proceeds upwards. Whilst the body still appears undiminished in size, the vaginal portion will be found already shorter, more slender, and more flaccid. Gradually, however, the entire organ is involved in the atrophic process. The uterus is then smaller than formerly, its walls are thinner, its cavity reduced in size. Its vascularity and its sensibility are alike diminished. The external os is smaller, and the internal os is sometimes entirely obliterated. There is a tendency at the climacteric period for the tubulo-racemose glands of the cervical mucous membrane (Fig. [92]) to undergo a cystic degeneration (Fig. [93]), and hence arise the cysts which are so commonly met with on the portio vaginalis of women at this time of life, cysts varying in size from that of a millet seed to that of a pea. In advanced life, the formation of such cysts may be regarded as normal, and sometimes in the form of grape-like clusters they almost completely occupy the lumen of the cervical canal. (Figs. 94, 95, 96, and 97).
Not infrequently, these cysts lead to the formation of polypi, by enlarging until the mucous membrane projects so far that a stalk is formed.
Examining the bodies of 47 women who died at ages varying from 42 to 80 years, I found in 28 ovula Nabothi in the cervical mucous membrane, for the most part at the os uteri externum, but in some cases also extending up to the os internum, sometimes between the plicae palmatae, sometimes isolated, sometimes grouped.
Sometimes in old women no trace of a vaginal portion remains, and the uterus is found to be transformed to a small, thin-walled, shrunken body, no more than one-fourth of its original size; in such cases the saying of Graaf appears to be justified, that after the menopause the uterus returns to the size it has in the young girl. In the majority of such cases, the cavity of the uterus is also contracted (concentric atrophy). It sometimes happens, however, that in old age the os externum and the os internum are the seat of atresia, whilst the intermediate portion of the cervical canal remains unaffected. In this way, especially when the cervical canal and the cavity of the body of the uterus are distended with mucus or with fungous growths, is produced what is known as the uterus bicameratus vetularum.
Fig. [95].—Ovula Nabothi in the Portio Vaginalis.
In many cases, when the cervical canal has been obliterated, we find the uterine cavity distended with mucous secretion (excentric atrophy). The substance of the uterine wall is in old age commonly dense and tough, but occasionally, in extreme old age, less firm than formerly, withered and friable, and traversed by degenerated arteries, and in this state it is predisposed to haemorrhages (apoplexia uteri). Such intramural haemorrhages usually occur in the fundus; the friable uterine substance has then a blackish-red appearance, infarcted with extravasated blood; sometimes the uterine cavity is also filled with blood. In general it may be said that when the menopause is completely over, when uterine activity has entirely ceased, the uterus returns to the state in which it was before the menarche—it is physiologically dead.
The tubes become flaccid, thinner, shorter, and are at times obliterated. In the mucous membrane of the tubes in old women we no longer find any trace of the glands described by Hennig; the epithelial cells have also lost their cilia.
During the climacteric period, the vagina is usually relaxed and roomy, the mucous membrane is smooth, injected and secretes freely; subsequently, in old age, it becomes firm, tough and dry.
Fig. [96].—Vesicle (Ovula Nabothi) from the Uterine Mucous Membrane.
Wendeler found that the initial change of the climacteric in the ovary is a chronic and progressive endarteritis obliterans; the result of this process is, in addition to the obliteration of the follicles, a continually increasing hyaline degeneration of the smallest arteries and the arterioles, especially along the line of transition between the cortical and the medullary substance of the organ; this degeneration extends to the surrounding connective tissue, and thus leads to the formation of peculiar, vitreous, translucent foci of sclerotic connective tissue, containing few cells or none; these are the so-called corpora fibrosa or corpora albicantia. Only subsequently to the formation of these bodies does the characteristic wrinkling of the surface of the ovary occur, with general shrinkage of the organ, these changes being due to the contraction that sets in in the numerous scattered foci of connective tissue, which, as already mentioned, are situated in close proximity to the cortex.
Fig. [97].—Mucous glands undergoing Cystic Degeneration.
The gradual atrophy of the uterus after the extinction of its sexual activity leads to a diminution in all the diameters of the organ, so that in old women it becomes flattened as in childhood, all its curves having disappeared; the muscular substance is replaced by connective tissue; and the portio vaginalis dwindles and even entirely disappears.
As regards the bacterial flora of the genital organs of elderly women, Menge and Koenig find that the vagina for the most part contains bacteria which do not thrive when cultivated aërobically on alkaline agar plates. In exceptional cases, however, such bacteria are found, and may even be sufficiently vigorous to produce pyogenic infection. According to Strogamoff, the vagina in all circumstances contains a great variety of micro-organisms—cocci, diplococci and rod-forms. Rod-forms are the prevailing types found in normal conditions in elderly women, but they are much smaller than in women who are still in the period of reproductive activity. Organisms liquefying gelatine were found in one instance only, a case of vaginal prolapse. In one half of the cases examined, there was no development of culture media inoculated from the cervix uteri, whether on agar or gelatine.